Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

bjancin@mdedge.com

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

bjancin@mdedge.com

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

Catheter-based renal denervation took a step closer to attaining legitimacy as a nonpharmacologic treatment for hypertension with presentation of the primary results of the SPYRAL HTN-OFF MED pivotal trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

Mohammed Haneefa Nizamudeen/Getty Images

“We saw clinically meaningful blood pressure reductions at 3 months,” reported Michael Boehm, MD, chief of cardiology at Saarland University Hospital in Homburg, Germany.

That’s encouraging news, as renal denervation (RDN) was nearly abandoned as a potential treatment for hypertension in the wake of the unexpectedly negative results of the SYMPLICITY HTN-3 trial (N Engl J Med. 2014;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution, and a more rigorous development program for the percutaneous device-based therapy is well underway.

The SPYRAL HTN-OFF MED pivotal trial was designed under Food and Drug Administration guidance to show whether RDN reduces blood pressure in patients with untreated hypertension. The prospective study included 331 off-medication patients in nine countries who were randomized to RDN or a sham procedure, then followed in double-blind fashion for 3 months.

The primary outcome was change in 24-hour ambulatory systolic blood pressure from baseline to 3 months. From a mean baseline 24-hour ambulatory blood pressure of 151.4/98 mm Hg, patients in the RDN group averaged a 4.7 mm Hg decrease in 24-hour SBP, which was 4 mm Hg more than in sham-treated controls. Statistically, this translated to a greater than 99.9% probability that RDN was superior to sham therapy. The RDN group also experienced a mean 3.7–mm Hg reduction in 24-hour DBP, compared with a 0.8–mm Hg decrease in controls.

Office SBP – the secondary endpoint – decreased by a mean of 9.2 mm Hg with RDN, compared with 2.5 mm Hg in controls.

These results probably understate the true antihypertensive effect of RDN for two reasons, Dr. Boehm noted. For one, previous studies have shown that the magnitude of blood pressure lowering continues to increase for up to 1-2 years following the procedure, whereas the off-medication assessment in SPYRAL HTN-OFF MED ended at 3 months for ethical and safety reasons. Also, 17% of patients in the control arm were withdrawn from the study and placed on antihypertensive medication because their office SBP reached 180 mm Hg or more, as compared to 9.6% of the RDN group.

A key finding was that RDN lowered blood pressure around the clock, including nighttime and early morning, the hours of greatest cardiovascular risk and a time when some antihypertensive medications are less effective at blood pressure control, the cardiologist observed.

The RDN safety picture was reassuring, with no strokes, myocardial infarctions, major bleeding, or acute deterioration in kidney function.

A surprising finding was that, even though participants underwent blood and urine testing for the presence of antihypertensive drugs at baseline to ensure they were off medication, and were told they would be retested at 3 months, 5%-9% nonetheless tested positive at the second test.

That elicited a comment from session chair Richard A. Chazal, MD, of Fort Myers, Fla.: “I must say, as a clinician who sometimes has trouble getting his patients to take antihypertensives, it’s fascinating that some of the people that you asked not to take the medications were taking them.”

While the primary outcome in SPYRAL HTN-OFF MED was the 3-month reduction in blood pressure while off of antihypertensive medication, the ongoing second phase of the trial may have greater clinical relevance. At 3 months, participants are being placed on antihypertensive medication and uptitrated to target, with unblinding at 6 months. The purpose is to see how many RDN recipients don’t need antihypertensive drugs, as well as whether those that do require less medication than the patients who didn’t undergo RDN.

Dr. Boehm characterized RDN as a work in progress. Two major limitations that are the focus of intense research are the lack of a predictor as to which patients are most likely to respond to what is after all an invasive procedure, and the current inability intraprocedurally to tell if sufficient RDN has been achieved.

“Frankly speaking, there is no technology during the procedure to see how efficacious the procedure was,” he explained.

Discussant Dhanunaja Lakkireddy, MD, deemed the mean 4.7–mm Hg reduction in 24-hour SBP “reasonably impressive – that’s actually a pretty good number for an antihypertensive clinical trial.” He was also favorably impressed by RDN’s safety in a 44-site study.

“The drops in blood pressure are not enough to really make a case for renal denervation to be a standalone therapy. But adding it as an adjunct to standard medications may be a very reasonable strategy to adopt. This is a fantastic signal for something that can be brought along as a long-term add-on to antihypertensive medications,” commented Dr. Lakkireddy, chair of the ACC Electrophysiology Council and medical director of the Kansas City Heart Rhythm Institute.

Simultaneous with Dr. Boehm’s presentation, the SPYRAL HTN-OFF MED Pivotal Trial details were published online (Lancet 2020 Mar 29. doi: 10.1016/S0140-6736(20)30554-7).

The study was sponsored by Medtronic. Dr. Boehm reported serving as a consultant to that company and Abbott, Amgen, Astra, Boehringer-Ingelheim, Cytokinetics, Novartis, ReCor, Servier, and Vifor.

bjancin@mdedge.com

SOURCE: Boehm M. ACC 2020, Abstract 406-15.

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

mzoler@mdedge.com

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

mzoler@mdedge.com

The long-sought goal of measuring the quality of U.S. transcatheter aortic valve replacement (TAVR) programs by patient outcomes rather than by the surrogate measure of case volume is about to be realized.

Starting more or less immediately, the U.S. national register for all TAVR cases that’s mandated by Food and Drug Administration labeling of these devices and run through a collaboration of the American College of Cardiology and the Society of Thoracic Surgeons will start applying a newly developed and validated five-item metric for measuring 30-day patient outcomes and designed to gauge the quality of TAVR programs.

At first, the only recipients of the data will be the programs themselves, but starting in about a year, by sometime in 2021, the STS/ACC TVT (transcatheter valve therapy) Registry will start to make its star-based rating of TAVR programs available to the public, Nimesh D. Desai, MD, said on March 29 at the joint scientific sessions of the ACC and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic. These societies already make star-based ratings of U.S. programs available to the public for several other types of cardiac interventions, including coronary artery bypass surgery and MI management.

The new, composite metric based on 30-day outcome data “is appropriate for high-stakes applications such as public reporting,” said Dr. Desai, a thoracic surgeon and director of thoracic aortic surgery research at the University of Pennsylvania in Philadelphia. “We’re confident this model can be used for public reporting. It’s undergone extensive testing of its validity.” The steering committee of the STS/ACC TVT Registry commissioned development of the metric, and it’s now “considered approved,” and ready for use, he explained.

To create the new metric, Dr. Desai and his associates used data from 52,561 patients who underwent transfemoral TAVR during 2015-2017 at any of 301 U.S. sites. These data came from a total pool of more than 114,000 patients at 556 sites, but data from many sites weren’t usable because they were not adequately complete. The researchers then identified the top four measures taken during the 30 days following intervention (hospitalization included) that best correlated with 1-year survival and patients’ quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire: stroke; major, life-threatening, or disabling bleed; acute kidney injury (stage III); and moderate or severe paravalvular leak. These outcomes “matter most to patients,” Dr. Desai said.

They used these four outcomes plus 30-day mortality to calculate the programs’ ratings. Among the 52,561 patients, 14% had at least one of these adverse outcomes. The researchers then used a logistic regression model that adjusted for 46 measured variables to calculate how each program performed relative to the average performance of all the programs. Programs with outcomes that fell within the 95% confidence intervals of average performance were rated as performing as expected; those outside rated as performing either better or worse than expected. The results showed 34 centers (11%) had worse than expected outcomes and 25 (8%) had better than expected outcomes, Dr. Desai said.

“This is a major step forward in measuring TAVR quality,” commented Michael Mack, MD, a cardiac surgeon with Baylor Scott & White Health in Dallas who has been very active in studying TAVR. “Until now, we used volume as a surrogate for quality, but the precision was not great. This is an extremely welcome metric.” The next step is to eventually use 1-year follow-up data instead of 30-day outcomes, he added.

“With the rapid expansion of TAVR over the past 6-8 years, we’re now at the point to start to do this. It’s an ethical obligation This will be one of the most high-fidelity, valid models for public reporting” of clinical outcomes,” said Joseph Cleveland, MD, a professor of surgery at the University of Colorado at Denver in Aurora. “It’s reassuring that about 90% of the program performed as expected or better than expected,” he added.

“Transparency and outcomes should drive how TAVR is delivered,” commented Ashish Pershad, MD, an interventional cardiologist at Banner-University Medicine Heart Institute in Phoenix who estimated that he performs about 150 TAVR procedures annually. “This is a step forward. I’ve been waiting for this for a long time. Until now, volume has been used as a surrogate outcome, but we know it’s not accurate. I’m confident that this model is a good starting point.” But Dr. Pershad also had concern that this new approach “can lend itself to some degree of gaming,” like a bleeding event getting classified as minor when it was really major, or outlier patients getting dropped from reports.

The temptation to cut corners may be higher for TAVR than it’s been for the cardiac-disease metrics that already get publicly reported, like bypass surgery and myocardial infarction management, because of TAVR’s higher cost and higher profile, Dr. Pershad said. Existing measures “have not been as linked to financial disincentive as TAVR might be” because TAVR reimbursements can run as high as $50,000 per case. “The stakes with TAVR are higher,” he said.

Ultimately, the reliable examination of TAVR outcomes that this new metric allows may lead to a shake-up of TAVR programs, Dr. Pershad predicted. “This is clearly a step toward closing down some programs that [consistently] underperform.”

The STS/ACC TVT Registry receives no commercial funding. Dr. Desai has been a consultant to, speaker on behalf of, and received research funding from Gore, and he has also spoken on behalf of Cook, Medtronic, and Terumo Aortic. Dr. Cleveland, Dr. Mack, and Dr. Pershad had no disclosures.

mzoler@mdedge.com

In the COMPASS trial of patients with stable coronary or peripheral artery disease (PAD), the combination of aspirin plus rivaroxaban, 2.5 mg twice daily, provided a larger absolute benefit on cardiovascular endpoints — including a threefold greater reduction in all-cause mortality — in patients with diabetes compared with the overall population.

The results of the diabetes subset of the COMPASS trial were presented by Deepak Bhatt, MD, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts, on March 28 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). They were also simultaneously published online in Circulation.

“Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients such as those with diabetes,” Bhatt concluded.

The COMPASS trial was first reported in 2017 and showed a new low dose of rivaroxaban (2.5-mg twice-daily; Xarelto, Bayer/Janssen Pharmaceuticals) plus aspirin, 100 mg once daily, was associated with a reduction in ischemic events and mortality and a superior net clinical benefit, balancing ischemic benefit with severe bleeding, compared with aspirin alone for secondary prevention in patients with stable atherosclerotic vascular disease.

But clinicians have been slow to prescribe rivaroxaban in this new and very large population.

“It’s been more than 2 years now since main COMPASS results, and there isn’t a sense that this therapy has really caught on,” chair of the current ACC session at which the diabetes subgroup results were presented, Hadley Wilson, MD, Sanger Heart and Vascular Institute, Charlotte, North Carolina, commented:

He asked Bhatt whether the diabetes subgroup may be “the tipping point that will make people aware of rivaroxaban and then that may trickle down to other patients.”

Bhatt said that he hoped that would be the case. “We as a steering committee of this trial could say the results were positive so rivaroxaban should now be used in everyone with stable coronary or peripheral arterial disease, but that is impractical and as you out point out it hasn’t happened,” he replied.

“In PAD/vascular medicine we have embraced this new therapy. In the broader cardiology world there are a lot of patients with stable coronary arterial disease at high ischemic risk who could take rivaroxaban, but its use is bound to be limited by it being a branded drug and the fact that there is a bleeding risk,” Bhatt explained.

“I think we need to identify patients with the highest ischemic risk and focus drugs such as these with a financial cost and a bleeding risk on those who most likely will derive the greatest absolute reduction in risk,” he said. “The PAD subgroup is one group where this is the case, and now we have shown the diabetes subgroup is another. And there is no incremental bleeding risk in this group over the whole population, so they get a much greater benefit without a greater risk. I hope this helps get rivaroxaban at the new lower dose used much more often.”

A total of 18,278 patients were randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone in the COMPASS trial. Of these, 6922 had diabetes mellitus at baseline and 11,356 did not have diabetes.

Results from the current analysis show a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin vs placebo plus aspirin in patients both with and without diabetes for the primary efficacy endpoint, a composite of cardiovascular death, myocardial infarction (MI), or stroke, with a hazard ratio of 0.74 for patients with diabetes and 0.77 for those without diabetes, the researchers report.

Because of the higher baseline risk in the diabetes subgroup, these patients had numerically larger absolute risk reductions with rivaroxaban than those without diabetes for the primary efficacy endpoint at 3 years (2.3% vs 1.4%) and for all-cause mortality (1.9% vs 0.6%).

These results translate into a number needed to treat (NNT) with rivaroxaban for 3 years to prevent one CV death, MI, or stroke of 44 for the diabetes group vs 73 for the nondiabetes group; the NNT to prevent one all-cause death was 54 for the diabetes group vs 167 for the nondiabetes group, the authors write.

Because the bleeding hazards were similar among patients with and without diabetes, the absolute net clinical benefit (MI, stroke, cardiovascular death, or bleeding leading to death or symptomatic bleeding into a critical organ) for rivaroxaban was “particularly favorable” in the diabetes group (2.7% fewer events in the diabetes group vs 1.0% fewer events in the nondiabetes group), they add.

Panelist at the ACC Featured Clinical Research session at which these results were presented, Jennifer Robinson, MD, University of Iowa College of Public Health, Iowa City, asked Bhatt how clinicians were supposed to decide which of the many new agents now becoming available for patients with stable coronary artery disease to prescribe first.

“We often forget about rivaroxaban when we’re thinking about what to add next for our secondary prevention patients,” she said. “You also led the REDUCE-IT trial showing benefit of icosapent ethyl, icosapent ethyl icosapent ethyl icosapent ethyl and there is also ezetimibe, PCSK9 inhibitors and SGLT2 inhibitors. For your patients with coronary disease who are already on a high dose statin which one of these would you add next?”

“That is what physicians need to ponder all the time,” Bhatt replied. “And when a patient has several risk factors that are not well controlled, I guess it’s all important. I go through a checklist with my patients and try and figure what they’re not on that could further reduce their risk.”

“In the COMPASS trial there was an overall positive result with rivaroxaban in the whole population. And now we have shown that patients with diabetes had an even greater absolute risk reduction. That pattern has also been seen with other classes of agents including the statins, PCSK9 inhibitors, and icosapent ethyl,” Bhatt noted.

“In patients with diabetes, I will usually target whatever is standing out most at that time. If their glycemic control is completely out of whack, then that is what I would focus on first, and these days often with a SGLT2 inhibitor or GLP-1 agonist. If the LDL was out of control, I would add ezetimibe or a PCSK9 inhibitor. If the triglycerides were high, I would add icosapent ethyl. If multiple things were out of control, I would usually focus on the number most out of kilter first and try not to forget about everything else.”

But Bhatt noted that the challenge with rivaroxaban is that there is no test of thrombosis risk that would prompt the physician to take action. “Basically, the doctor just has to remember to do it. In that regard I would consider whether patients are at low bleeding risk and are they still at high ischemic risk despite controlling other risk factors and, if so, then I would add this low dose of rivaroxaban.”

Another panel member, Sekar Kathiresan, MD, asked Bhatt whether he recommended using available scores to assess the bleeding/thrombosis risk/benefits of adding an antithrombotic.

Bhatt replied: “That’s a terrific question. I guess the right answer is that we should be doing that, but in reality I have to concede that I don’t use these scores. They have shown appropriate C statistics in populations, but they are not fantastic in individual patients.”

“I have to confess that I use the eyeball test. There is nothing as good at predicting future bleeding as past bleeding. So if a patient has had bleeding problems on aspirin alone I wouldn’t add rivaroxaban. But if a patient hasn’t bled before, especially if they had some experience of dual antiplatelet therapy, then they would be good candidates for a low vascular dose of rivaroxaban,” he said.

“It is not as easy as with other drugs as there is always a bleeding trade-off with an antithrombotic. There is no such thing as a free lunch. So patients need careful assessment when considering prescribing rivaroxaban and regular reassessment over time to check if they have had any bleeding,” he added.

The COMPASS study was funded by Bayer. Bhatt reports honoraria from Bayer via the Population Health Research Institute for his role on the COMPASS trial and other research funding from Bayer to the Brigham & Women’s Hospital.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20544-ACC. Presented March 28, 2020.

Circulation. Published online March 28, 2020. Full text.

This article first appeared on Medscape.com.

In the COMPASS trial of patients with stable coronary or peripheral artery disease (PAD), the combination of aspirin plus rivaroxaban, 2.5 mg twice daily, provided a larger absolute benefit on cardiovascular endpoints — including a threefold greater reduction in all-cause mortality — in patients with diabetes compared with the overall population.

The results of the diabetes subset of the COMPASS trial were presented by Deepak Bhatt, MD, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts, on March 28 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). They were also simultaneously published online in Circulation.

“Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients such as those with diabetes,” Bhatt concluded.

The COMPASS trial was first reported in 2017 and showed a new low dose of rivaroxaban (2.5-mg twice-daily; Xarelto, Bayer/Janssen Pharmaceuticals) plus aspirin, 100 mg once daily, was associated with a reduction in ischemic events and mortality and a superior net clinical benefit, balancing ischemic benefit with severe bleeding, compared with aspirin alone for secondary prevention in patients with stable atherosclerotic vascular disease.

But clinicians have been slow to prescribe rivaroxaban in this new and very large population.

“It’s been more than 2 years now since main COMPASS results, and there isn’t a sense that this therapy has really caught on,” chair of the current ACC session at which the diabetes subgroup results were presented, Hadley Wilson, MD, Sanger Heart and Vascular Institute, Charlotte, North Carolina, commented:

He asked Bhatt whether the diabetes subgroup may be “the tipping point that will make people aware of rivaroxaban and then that may trickle down to other patients.”

Bhatt said that he hoped that would be the case. “We as a steering committee of this trial could say the results were positive so rivaroxaban should now be used in everyone with stable coronary or peripheral arterial disease, but that is impractical and as you out point out it hasn’t happened,” he replied.

“In PAD/vascular medicine we have embraced this new therapy. In the broader cardiology world there are a lot of patients with stable coronary arterial disease at high ischemic risk who could take rivaroxaban, but its use is bound to be limited by it being a branded drug and the fact that there is a bleeding risk,” Bhatt explained.

“I think we need to identify patients with the highest ischemic risk and focus drugs such as these with a financial cost and a bleeding risk on those who most likely will derive the greatest absolute reduction in risk,” he said. “The PAD subgroup is one group where this is the case, and now we have shown the diabetes subgroup is another. And there is no incremental bleeding risk in this group over the whole population, so they get a much greater benefit without a greater risk. I hope this helps get rivaroxaban at the new lower dose used much more often.”

A total of 18,278 patients were randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone in the COMPASS trial. Of these, 6922 had diabetes mellitus at baseline and 11,356 did not have diabetes.

Results from the current analysis show a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin vs placebo plus aspirin in patients both with and without diabetes for the primary efficacy endpoint, a composite of cardiovascular death, myocardial infarction (MI), or stroke, with a hazard ratio of 0.74 for patients with diabetes and 0.77 for those without diabetes, the researchers report.

Because of the higher baseline risk in the diabetes subgroup, these patients had numerically larger absolute risk reductions with rivaroxaban than those without diabetes for the primary efficacy endpoint at 3 years (2.3% vs 1.4%) and for all-cause mortality (1.9% vs 0.6%).

These results translate into a number needed to treat (NNT) with rivaroxaban for 3 years to prevent one CV death, MI, or stroke of 44 for the diabetes group vs 73 for the nondiabetes group; the NNT to prevent one all-cause death was 54 for the diabetes group vs 167 for the nondiabetes group, the authors write.

Because the bleeding hazards were similar among patients with and without diabetes, the absolute net clinical benefit (MI, stroke, cardiovascular death, or bleeding leading to death or symptomatic bleeding into a critical organ) for rivaroxaban was “particularly favorable” in the diabetes group (2.7% fewer events in the diabetes group vs 1.0% fewer events in the nondiabetes group), they add.

Panelist at the ACC Featured Clinical Research session at which these results were presented, Jennifer Robinson, MD, University of Iowa College of Public Health, Iowa City, asked Bhatt how clinicians were supposed to decide which of the many new agents now becoming available for patients with stable coronary artery disease to prescribe first.

“We often forget about rivaroxaban when we’re thinking about what to add next for our secondary prevention patients,” she said. “You also led the REDUCE-IT trial showing benefit of icosapent ethyl, icosapent ethyl icosapent ethyl icosapent ethyl and there is also ezetimibe, PCSK9 inhibitors and SGLT2 inhibitors. For your patients with coronary disease who are already on a high dose statin which one of these would you add next?”

“That is what physicians need to ponder all the time,” Bhatt replied. “And when a patient has several risk factors that are not well controlled, I guess it’s all important. I go through a checklist with my patients and try and figure what they’re not on that could further reduce their risk.”

“In the COMPASS trial there was an overall positive result with rivaroxaban in the whole population. And now we have shown that patients with diabetes had an even greater absolute risk reduction. That pattern has also been seen with other classes of agents including the statins, PCSK9 inhibitors, and icosapent ethyl,” Bhatt noted.

“In patients with diabetes, I will usually target whatever is standing out most at that time. If their glycemic control is completely out of whack, then that is what I would focus on first, and these days often with a SGLT2 inhibitor or GLP-1 agonist. If the LDL was out of control, I would add ezetimibe or a PCSK9 inhibitor. If the triglycerides were high, I would add icosapent ethyl. If multiple things were out of control, I would usually focus on the number most out of kilter first and try not to forget about everything else.”

But Bhatt noted that the challenge with rivaroxaban is that there is no test of thrombosis risk that would prompt the physician to take action. “Basically, the doctor just has to remember to do it. In that regard I would consider whether patients are at low bleeding risk and are they still at high ischemic risk despite controlling other risk factors and, if so, then I would add this low dose of rivaroxaban.”

Another panel member, Sekar Kathiresan, MD, asked Bhatt whether he recommended using available scores to assess the bleeding/thrombosis risk/benefits of adding an antithrombotic.

Bhatt replied: “That’s a terrific question. I guess the right answer is that we should be doing that, but in reality I have to concede that I don’t use these scores. They have shown appropriate C statistics in populations, but they are not fantastic in individual patients.”

“I have to confess that I use the eyeball test. There is nothing as good at predicting future bleeding as past bleeding. So if a patient has had bleeding problems on aspirin alone I wouldn’t add rivaroxaban. But if a patient hasn’t bled before, especially if they had some experience of dual antiplatelet therapy, then they would be good candidates for a low vascular dose of rivaroxaban,” he said.

“It is not as easy as with other drugs as there is always a bleeding trade-off with an antithrombotic. There is no such thing as a free lunch. So patients need careful assessment when considering prescribing rivaroxaban and regular reassessment over time to check if they have had any bleeding,” he added.

The COMPASS study was funded by Bayer. Bhatt reports honoraria from Bayer via the Population Health Research Institute for his role on the COMPASS trial and other research funding from Bayer to the Brigham & Women’s Hospital.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20544-ACC. Presented March 28, 2020.

Circulation. Published online March 28, 2020. Full text.

This article first appeared on Medscape.com.

In the COMPASS trial of patients with stable coronary or peripheral artery disease (PAD), the combination of aspirin plus rivaroxaban, 2.5 mg twice daily, provided a larger absolute benefit on cardiovascular endpoints — including a threefold greater reduction in all-cause mortality — in patients with diabetes compared with the overall population.

The results of the diabetes subset of the COMPASS trial were presented by Deepak Bhatt, MD, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts, on March 28 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). They were also simultaneously published online in Circulation.

“Use of dual pathway inhibition with low-dose rivaroxaban plus aspirin is particularly attractive in high-risk patients such as those with diabetes,” Bhatt concluded.

The COMPASS trial was first reported in 2017 and showed a new low dose of rivaroxaban (2.5-mg twice-daily; Xarelto, Bayer/Janssen Pharmaceuticals) plus aspirin, 100 mg once daily, was associated with a reduction in ischemic events and mortality and a superior net clinical benefit, balancing ischemic benefit with severe bleeding, compared with aspirin alone for secondary prevention in patients with stable atherosclerotic vascular disease.

But clinicians have been slow to prescribe rivaroxaban in this new and very large population.

“It’s been more than 2 years now since main COMPASS results, and there isn’t a sense that this therapy has really caught on,” chair of the current ACC session at which the diabetes subgroup results were presented, Hadley Wilson, MD, Sanger Heart and Vascular Institute, Charlotte, North Carolina, commented:

He asked Bhatt whether the diabetes subgroup may be “the tipping point that will make people aware of rivaroxaban and then that may trickle down to other patients.”

Bhatt said that he hoped that would be the case. “We as a steering committee of this trial could say the results were positive so rivaroxaban should now be used in everyone with stable coronary or peripheral arterial disease, but that is impractical and as you out point out it hasn’t happened,” he replied.

“In PAD/vascular medicine we have embraced this new therapy. In the broader cardiology world there are a lot of patients with stable coronary arterial disease at high ischemic risk who could take rivaroxaban, but its use is bound to be limited by it being a branded drug and the fact that there is a bleeding risk,” Bhatt explained.

“I think we need to identify patients with the highest ischemic risk and focus drugs such as these with a financial cost and a bleeding risk on those who most likely will derive the greatest absolute reduction in risk,” he said. “The PAD subgroup is one group where this is the case, and now we have shown the diabetes subgroup is another. And there is no incremental bleeding risk in this group over the whole population, so they get a much greater benefit without a greater risk. I hope this helps get rivaroxaban at the new lower dose used much more often.”

A total of 18,278 patients were randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone in the COMPASS trial. Of these, 6922 had diabetes mellitus at baseline and 11,356 did not have diabetes.

Results from the current analysis show a consistent and similar relative risk reduction for benefit of rivaroxaban plus aspirin vs placebo plus aspirin in patients both with and without diabetes for the primary efficacy endpoint, a composite of cardiovascular death, myocardial infarction (MI), or stroke, with a hazard ratio of 0.74 for patients with diabetes and 0.77 for those without diabetes, the researchers report.

Because of the higher baseline risk in the diabetes subgroup, these patients had numerically larger absolute risk reductions with rivaroxaban than those without diabetes for the primary efficacy endpoint at 3 years (2.3% vs 1.4%) and for all-cause mortality (1.9% vs 0.6%).

These results translate into a number needed to treat (NNT) with rivaroxaban for 3 years to prevent one CV death, MI, or stroke of 44 for the diabetes group vs 73 for the nondiabetes group; the NNT to prevent one all-cause death was 54 for the diabetes group vs 167 for the nondiabetes group, the authors write.

Because the bleeding hazards were similar among patients with and without diabetes, the absolute net clinical benefit (MI, stroke, cardiovascular death, or bleeding leading to death or symptomatic bleeding into a critical organ) for rivaroxaban was “particularly favorable” in the diabetes group (2.7% fewer events in the diabetes group vs 1.0% fewer events in the nondiabetes group), they add.

Panelist at the ACC Featured Clinical Research session at which these results were presented, Jennifer Robinson, MD, University of Iowa College of Public Health, Iowa City, asked Bhatt how clinicians were supposed to decide which of the many new agents now becoming available for patients with stable coronary artery disease to prescribe first.

“We often forget about rivaroxaban when we’re thinking about what to add next for our secondary prevention patients,” she said. “You also led the REDUCE-IT trial showing benefit of icosapent ethyl, icosapent ethyl icosapent ethyl icosapent ethyl and there is also ezetimibe, PCSK9 inhibitors and SGLT2 inhibitors. For your patients with coronary disease who are already on a high dose statin which one of these would you add next?”

“That is what physicians need to ponder all the time,” Bhatt replied. “And when a patient has several risk factors that are not well controlled, I guess it’s all important. I go through a checklist with my patients and try and figure what they’re not on that could further reduce their risk.”

“In the COMPASS trial there was an overall positive result with rivaroxaban in the whole population. And now we have shown that patients with diabetes had an even greater absolute risk reduction. That pattern has also been seen with other classes of agents including the statins, PCSK9 inhibitors, and icosapent ethyl,” Bhatt noted.

“In patients with diabetes, I will usually target whatever is standing out most at that time. If their glycemic control is completely out of whack, then that is what I would focus on first, and these days often with a SGLT2 inhibitor or GLP-1 agonist. If the LDL was out of control, I would add ezetimibe or a PCSK9 inhibitor. If the triglycerides were high, I would add icosapent ethyl. If multiple things were out of control, I would usually focus on the number most out of kilter first and try not to forget about everything else.”

But Bhatt noted that the challenge with rivaroxaban is that there is no test of thrombosis risk that would prompt the physician to take action. “Basically, the doctor just has to remember to do it. In that regard I would consider whether patients are at low bleeding risk and are they still at high ischemic risk despite controlling other risk factors and, if so, then I would add this low dose of rivaroxaban.”

Another panel member, Sekar Kathiresan, MD, asked Bhatt whether he recommended using available scores to assess the bleeding/thrombosis risk/benefits of adding an antithrombotic.

Bhatt replied: “That’s a terrific question. I guess the right answer is that we should be doing that, but in reality I have to concede that I don’t use these scores. They have shown appropriate C statistics in populations, but they are not fantastic in individual patients.”

“I have to confess that I use the eyeball test. There is nothing as good at predicting future bleeding as past bleeding. So if a patient has had bleeding problems on aspirin alone I wouldn’t add rivaroxaban. But if a patient hasn’t bled before, especially if they had some experience of dual antiplatelet therapy, then they would be good candidates for a low vascular dose of rivaroxaban,” he said.

“It is not as easy as with other drugs as there is always a bleeding trade-off with an antithrombotic. There is no such thing as a free lunch. So patients need careful assessment when considering prescribing rivaroxaban and regular reassessment over time to check if they have had any bleeding,” he added.

The COMPASS study was funded by Bayer. Bhatt reports honoraria from Bayer via the Population Health Research Institute for his role on the COMPASS trial and other research funding from Bayer to the Brigham & Women’s Hospital.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20544-ACC. Presented March 28, 2020.

Circulation. Published online March 28, 2020. Full text.

This article first appeared on Medscape.com.

Every year, the Centers for Medicare & Medicaid Services (CMS) releases their proposed recommendations for the next performance year and in 2019, the gastroenterology community was surprised that CMS recommended removal of QPP 0343 – Screening Colonoscopy Adenoma Detection Rate from a reportable measure in the Quality Payment Program. So what happened? Why was the measure removed from the QPP? Is there anything that we can do?

Over the next several months we will be publishing a series of articles related to the Adenoma Detection Rate Measure to give every gastroenterologist an inside look at the work that is done on your behalf and steps that you can take in the future to help your fellow gastroenterologists.

This current article explains the joint effort made by all GI societies to try to save the Adenoma Detection Rate measure from removal from the 2020 Quality Payment Program. All societies uniformly submitted a letter to CMS in disapproval of the recommendation and outlined the importance of this measure as follows:
 

Measure 343: Screening Colonoscopy Adenoma Detection Rate

Our societies are disappointed and disagree with CMS’s decision to remove Measure 343: Screening Colonoscopy Adenoma Detection Rate (ADR) from the Quality Payment Program (QPP) beginning with the 2020 performance year.

The ADR plays a central role in quality improvement and colorectal cancer screening. We urge CMS to reconsider this decision and issue a technical correction to reinstate the measure back into the QPP, as it is the only outcome measure specific to endoscopic skills of gastroenterologists currently available for public reporting.

Studies show that high adenoma detection rates are associated with a significant reduction in colorectal cancer risk.¹ Virtually all studies on this subject have demonstrated that there is, in fact, marked variation in adenoma detection rates among physicians. Further, ADR is essential to recommended intervals² between screening and surveillance examinations.^2,3

1. Variables influencing ADR. CMS explained that the measure does not account for variables that may influence the ADR such as geographic location, socioeconomic status of patient population, community compliance of screening, etc. The agency further states that according to the risk factors outlined by the American Cancer Society, African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the United States. “In addition, dietary factors, such as consumption of highly processed meats will contribute to an increased risk of colorectal cancer. This diet is more prevalent in lower socioeconomic areas, which could influence the outcome of the measure. There are other patient factors like education, health literacy, etc. that might also affect things like the adequacy of bowel preparation, which in turn could affect performance.”

The societies advised CMS that this rationale reflects a misunderstanding of the definition of ADR, which includes all average-risk patients in whom the physician finds at least one adenoma. Further, ADR only includes colonoscopies with adequate bowel preparation and complete examinations. Studies demonstrate that ADR is not influenced by socioeconomic status and sex mix of the provider’s patient population, or by the rate of screening in the community.

Socioeconomics, ethnicity, and diet are not relevant factors of ADR. That said, our societies welcome the opportunity to work with CMS on creating age and sex standardized ADRs for the U.S. population, if feasible, in order to capture information that CMS deems important.

2. Failure to detect all adenomas. CMS stated that the measure does not account for MIPS eligible clinicians that fail to detect adenomas but may score higher based on the patient population.

The societies pushed back with CMS explaining that this rationale again reflects a misunderstanding of the definition of ADR, which includes average-risk patients for whom the physician finds at least one adenoma. Colonoscopy is heavily operator dependent. In an average-risk, mixed population, the variability in ADR reflects quality of the provider’s endoscopic skills and pathology recognition, rather than the risk of the underlying population.

3. Incidence measure. CMS concluded that Measure 343: Screening Colonoscopy Adenoma Detection Rate is considered an “incidence measure” that does not assess the quality of the care provided. In essence, according to CMS, the measure is based on happenstance rather than the eligible clinician providing a thorough examination.

The societies strongly disagreed with this characterization of ADR. Measure 343: Screening Colonoscopy Adenoma Detection Rate is the only measure that assess the quality of the exam performed by the physician in an average-risk patient with an adequate bowel preparation. Physicians can improve their adenoma detection rate by paying attention to detail, spending more time looking for adenomas, and learning better techniques.

4. Benchmarking. CMS stated that because of the measure construct, benchmarks calculated from this measure are misrepresented and do not align with the MIPS scoring methodology where 100% indicates better clinical care or control. Guidelines and supplemental literature support a performance target for adenoma detection rate of 25% for a mixed sex population (20% in women and 30% in men). CMS determined that Measure 343: Screening Colonoscopy Adenoma Detection Rate may be appropriate for other programs but does not align with the scoring logic within MIPS. When this measure was introduced, according to the agency, it was under the legacy program, Physician Quality Reporting System (PQRS), a pay-for-reporting program that does not have the same scoring implications as MIPS.

The societies reminded CMS that the 25% is the minimum requirement for performance and is not a benchmark. This minimum requirement continues to increase as well. With 25% being the threshold, for every 1% increase in ADR the risk of fatal interval colon cancer decreases by 3%. In one important study by Corley et al, the lowest quintile of ADR was 19% or lower, and was associated with the highest risk of interval colon cancer.⁴

CMS must begin to move beyond traditional approaches toward benchmarking performance where 100% compliance is expected. It was encouraging to see CMS acknowledge that nuances to evaluating scores are needed based on the ability of a measure to accurately identify and capture performance based on the patient population and measure specifications. For example, these adjustments were finalized for the blood pressure and diabetes HbA_1c measures, where the highest number of points will be achieved for anyone scoring 90% or higher. This modification was based on the knowledge that it is not realistic nor in the interest of patients to assume that clinicians will be able to achieve the desired targeted outcome for every patient. The potential for unintended consequences was factored into an assessment of what performance could be considered achievable.

In our view, ADR is a similar example where 100% performance across a clinician’s population of patients is biologically impossible since not every individual who receives a screening colonoscopy will have an adenoma detected. ADR is the best-established colorectal neoplasia-related quality indicator and research demonstrates that high rates are associated with significant reductions in colorectal cancer risk.

CMS must continue to explore alternative strategies toward benchmarking in MIPS to ensure that achievement is fairly assessed, and top performance scores are determined not solely based on peer performance but also based on clinical evidence balanced with minimizing unintended consequences. The MIPS program and its benchmarking and scoring methodologies must continue to innovate to ensure that physicians provide the best possible care to their patients while also accurately and fairly representing and rewarding clinicians’ performance. Continuing to promote a siloed view toward quality will only reduce the relevance of the MIPS program and lead our members to question the integrity and validity of the program.

References

1. Kaminski MF, Regula J, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. 2010;362(19):1795-803.

2. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844-57.

3. Rubin CE, Haggitt RC, Burmer GC, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology. 1992;103:1611-20.

4. Corley D, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-306.

5. Kaminski MF, et al. Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death. Gastroenterology. 2017 Jul;153[1]:98-105. doi: 10.1053/j.gastro.2017.04.006. Epub 2017 Apr 17.

6. ASGE practice guideline: Measuring the quality of endoscopy. Gastrointest Endosc. 2006;58:S1-S38.

7. Rex DK. Colonoscopic withdrawal technique is associated with adenoma miss rate. Gastrointest Endosc. 2000;51:33-6.

8. Barclay RL, et al. Effect of a time-dependent colonoscopic withdrawal protocol on adenoma detection during screening colonoscopy. Clin Gastroenterol Hepatol. 2008;6:1091-8.

9. Shaukat A, et al. Longer withdrawal time is associated with a reduced incidence of interval cancer after screening colonoscopy. Gastroenterology. 2015 Oct;149[4]:952-7

10. Lee S, et al. Am J Gastroenterol. 2016 Jan;111(1):63-9.

11. Jia H, et al. Water exchange method significantly improves adenoma detection rate: A multicenter, randomized controlled trial. Am J Gastroenterol. 2017;112(4):568-76.

12. ASGE. Endoscopes and devices to improve colon polyp detection. GIE 2015;81:1122-9.

13. Ussui V, et al. Am J Gastroenterol. 2015;110:489-96.

14. Kaminski MF, et al. Leadership training to improve adenoma detection rate in screening colonoscopy: a randomized trial. Gut 2016;65:616-24.

15. Shaukat A, et al. Rates of detection of adenoma, sessile serrated adenoma, and advanced adenoma are stable over time and modifiable. Gastroenterology 2018(Feb);156:816-7.

Dr. Adams is a gastroenterologist and assistant professor at the University of Michigan, Ann Arbor; Dr. Leiman is a gastroenterologist and assistant professor of medicine at Duke Health, Durham, N.C.; Dr. Mathews is a gastroenterologist and leader of Clinical Innovation at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, Baltimore.

Every year, the Centers for Medicare & Medicaid Services (CMS) releases their proposed recommendations for the next performance year and in 2019, the gastroenterology community was surprised that CMS recommended removal of QPP 0343 – Screening Colonoscopy Adenoma Detection Rate from a reportable measure in the Quality Payment Program. So what happened? Why was the measure removed from the QPP? Is there anything that we can do?

Over the next several months we will be publishing a series of articles related to the Adenoma Detection Rate Measure to give every gastroenterologist an inside look at the work that is done on your behalf and steps that you can take in the future to help your fellow gastroenterologists.

This current article explains the joint effort made by all GI societies to try to save the Adenoma Detection Rate measure from removal from the 2020 Quality Payment Program. All societies uniformly submitted a letter to CMS in disapproval of the recommendation and outlined the importance of this measure as follows:
 

Measure 343: Screening Colonoscopy Adenoma Detection Rate

Our societies are disappointed and disagree with CMS’s decision to remove Measure 343: Screening Colonoscopy Adenoma Detection Rate (ADR) from the Quality Payment Program (QPP) beginning with the 2020 performance year.

The ADR plays a central role in quality improvement and colorectal cancer screening. We urge CMS to reconsider this decision and issue a technical correction to reinstate the measure back into the QPP, as it is the only outcome measure specific to endoscopic skills of gastroenterologists currently available for public reporting.

Studies show that high adenoma detection rates are associated with a significant reduction in colorectal cancer risk.¹ Virtually all studies on this subject have demonstrated that there is, in fact, marked variation in adenoma detection rates among physicians. Further, ADR is essential to recommended intervals² between screening and surveillance examinations.^2,3

1. Variables influencing ADR. CMS explained that the measure does not account for variables that may influence the ADR such as geographic location, socioeconomic status of patient population, community compliance of screening, etc. The agency further states that according to the risk factors outlined by the American Cancer Society, African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the United States. “In addition, dietary factors, such as consumption of highly processed meats will contribute to an increased risk of colorectal cancer. This diet is more prevalent in lower socioeconomic areas, which could influence the outcome of the measure. There are other patient factors like education, health literacy, etc. that might also affect things like the adequacy of bowel preparation, which in turn could affect performance.”

The societies advised CMS that this rationale reflects a misunderstanding of the definition of ADR, which includes all average-risk patients in whom the physician finds at least one adenoma. Further, ADR only includes colonoscopies with adequate bowel preparation and complete examinations. Studies demonstrate that ADR is not influenced by socioeconomic status and sex mix of the provider’s patient population, or by the rate of screening in the community.

Socioeconomics, ethnicity, and diet are not relevant factors of ADR. That said, our societies welcome the opportunity to work with CMS on creating age and sex standardized ADRs for the U.S. population, if feasible, in order to capture information that CMS deems important.

2. Failure to detect all adenomas. CMS stated that the measure does not account for MIPS eligible clinicians that fail to detect adenomas but may score higher based on the patient population.

The societies pushed back with CMS explaining that this rationale again reflects a misunderstanding of the definition of ADR, which includes average-risk patients for whom the physician finds at least one adenoma. Colonoscopy is heavily operator dependent. In an average-risk, mixed population, the variability in ADR reflects quality of the provider’s endoscopic skills and pathology recognition, rather than the risk of the underlying population.

3. Incidence measure. CMS concluded that Measure 343: Screening Colonoscopy Adenoma Detection Rate is considered an “incidence measure” that does not assess the quality of the care provided. In essence, according to CMS, the measure is based on happenstance rather than the eligible clinician providing a thorough examination.

The societies strongly disagreed with this characterization of ADR. Measure 343: Screening Colonoscopy Adenoma Detection Rate is the only measure that assess the quality of the exam performed by the physician in an average-risk patient with an adequate bowel preparation. Physicians can improve their adenoma detection rate by paying attention to detail, spending more time looking for adenomas, and learning better techniques.

4. Benchmarking. CMS stated that because of the measure construct, benchmarks calculated from this measure are misrepresented and do not align with the MIPS scoring methodology where 100% indicates better clinical care or control. Guidelines and supplemental literature support a performance target for adenoma detection rate of 25% for a mixed sex population (20% in women and 30% in men). CMS determined that Measure 343: Screening Colonoscopy Adenoma Detection Rate may be appropriate for other programs but does not align with the scoring logic within MIPS. When this measure was introduced, according to the agency, it was under the legacy program, Physician Quality Reporting System (PQRS), a pay-for-reporting program that does not have the same scoring implications as MIPS.

The societies reminded CMS that the 25% is the minimum requirement for performance and is not a benchmark. This minimum requirement continues to increase as well. With 25% being the threshold, for every 1% increase in ADR the risk of fatal interval colon cancer decreases by 3%. In one important study by Corley et al, the lowest quintile of ADR was 19% or lower, and was associated with the highest risk of interval colon cancer.⁴

CMS must begin to move beyond traditional approaches toward benchmarking performance where 100% compliance is expected. It was encouraging to see CMS acknowledge that nuances to evaluating scores are needed based on the ability of a measure to accurately identify and capture performance based on the patient population and measure specifications. For example, these adjustments were finalized for the blood pressure and diabetes HbA_1c measures, where the highest number of points will be achieved for anyone scoring 90% or higher. This modification was based on the knowledge that it is not realistic nor in the interest of patients to assume that clinicians will be able to achieve the desired targeted outcome for every patient. The potential for unintended consequences was factored into an assessment of what performance could be considered achievable.

In our view, ADR is a similar example where 100% performance across a clinician’s population of patients is biologically impossible since not every individual who receives a screening colonoscopy will have an adenoma detected. ADR is the best-established colorectal neoplasia-related quality indicator and research demonstrates that high rates are associated with significant reductions in colorectal cancer risk.

CMS must continue to explore alternative strategies toward benchmarking in MIPS to ensure that achievement is fairly assessed, and top performance scores are determined not solely based on peer performance but also based on clinical evidence balanced with minimizing unintended consequences. The MIPS program and its benchmarking and scoring methodologies must continue to innovate to ensure that physicians provide the best possible care to their patients while also accurately and fairly representing and rewarding clinicians’ performance. Continuing to promote a siloed view toward quality will only reduce the relevance of the MIPS program and lead our members to question the integrity and validity of the program.

References

1. Kaminski MF, Regula J, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. 2010;362(19):1795-803.

2. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844-57.

3. Rubin CE, Haggitt RC, Burmer GC, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology. 1992;103:1611-20.

4. Corley D, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-306.

5. Kaminski MF, et al. Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death. Gastroenterology. 2017 Jul;153[1]:98-105. doi: 10.1053/j.gastro.2017.04.006. Epub 2017 Apr 17.

6. ASGE practice guideline: Measuring the quality of endoscopy. Gastrointest Endosc. 2006;58:S1-S38.

7. Rex DK. Colonoscopic withdrawal technique is associated with adenoma miss rate. Gastrointest Endosc. 2000;51:33-6.

8. Barclay RL, et al. Effect of a time-dependent colonoscopic withdrawal protocol on adenoma detection during screening colonoscopy. Clin Gastroenterol Hepatol. 2008;6:1091-8.

9. Shaukat A, et al. Longer withdrawal time is associated with a reduced incidence of interval cancer after screening colonoscopy. Gastroenterology. 2015 Oct;149[4]:952-7

10. Lee S, et al. Am J Gastroenterol. 2016 Jan;111(1):63-9.

11. Jia H, et al. Water exchange method significantly improves adenoma detection rate: A multicenter, randomized controlled trial. Am J Gastroenterol. 2017;112(4):568-76.

12. ASGE. Endoscopes and devices to improve colon polyp detection. GIE 2015;81:1122-9.

13. Ussui V, et al. Am J Gastroenterol. 2015;110:489-96.

14. Kaminski MF, et al. Leadership training to improve adenoma detection rate in screening colonoscopy: a randomized trial. Gut 2016;65:616-24.

15. Shaukat A, et al. Rates of detection of adenoma, sessile serrated adenoma, and advanced adenoma are stable over time and modifiable. Gastroenterology 2018(Feb);156:816-7.

Dr. Adams is a gastroenterologist and assistant professor at the University of Michigan, Ann Arbor; Dr. Leiman is a gastroenterologist and assistant professor of medicine at Duke Health, Durham, N.C.; Dr. Mathews is a gastroenterologist and leader of Clinical Innovation at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, Baltimore.

Every year, the Centers for Medicare & Medicaid Services (CMS) releases their proposed recommendations for the next performance year and in 2019, the gastroenterology community was surprised that CMS recommended removal of QPP 0343 – Screening Colonoscopy Adenoma Detection Rate from a reportable measure in the Quality Payment Program. So what happened? Why was the measure removed from the QPP? Is there anything that we can do?

Over the next several months we will be publishing a series of articles related to the Adenoma Detection Rate Measure to give every gastroenterologist an inside look at the work that is done on your behalf and steps that you can take in the future to help your fellow gastroenterologists.

This current article explains the joint effort made by all GI societies to try to save the Adenoma Detection Rate measure from removal from the 2020 Quality Payment Program. All societies uniformly submitted a letter to CMS in disapproval of the recommendation and outlined the importance of this measure as follows:
 

Measure 343: Screening Colonoscopy Adenoma Detection Rate

Our societies are disappointed and disagree with CMS’s decision to remove Measure 343: Screening Colonoscopy Adenoma Detection Rate (ADR) from the Quality Payment Program (QPP) beginning with the 2020 performance year.

The ADR plays a central role in quality improvement and colorectal cancer screening. We urge CMS to reconsider this decision and issue a technical correction to reinstate the measure back into the QPP, as it is the only outcome measure specific to endoscopic skills of gastroenterologists currently available for public reporting.

Studies show that high adenoma detection rates are associated with a significant reduction in colorectal cancer risk.¹ Virtually all studies on this subject have demonstrated that there is, in fact, marked variation in adenoma detection rates among physicians. Further, ADR is essential to recommended intervals² between screening and surveillance examinations.^2,3

1. Variables influencing ADR. CMS explained that the measure does not account for variables that may influence the ADR such as geographic location, socioeconomic status of patient population, community compliance of screening, etc. The agency further states that according to the risk factors outlined by the American Cancer Society, African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the United States. “In addition, dietary factors, such as consumption of highly processed meats will contribute to an increased risk of colorectal cancer. This diet is more prevalent in lower socioeconomic areas, which could influence the outcome of the measure. There are other patient factors like education, health literacy, etc. that might also affect things like the adequacy of bowel preparation, which in turn could affect performance.”

The societies advised CMS that this rationale reflects a misunderstanding of the definition of ADR, which includes all average-risk patients in whom the physician finds at least one adenoma. Further, ADR only includes colonoscopies with adequate bowel preparation and complete examinations. Studies demonstrate that ADR is not influenced by socioeconomic status and sex mix of the provider’s patient population, or by the rate of screening in the community.

Socioeconomics, ethnicity, and diet are not relevant factors of ADR. That said, our societies welcome the opportunity to work with CMS on creating age and sex standardized ADRs for the U.S. population, if feasible, in order to capture information that CMS deems important.

2. Failure to detect all adenomas. CMS stated that the measure does not account for MIPS eligible clinicians that fail to detect adenomas but may score higher based on the patient population.

The societies pushed back with CMS explaining that this rationale again reflects a misunderstanding of the definition of ADR, which includes average-risk patients for whom the physician finds at least one adenoma. Colonoscopy is heavily operator dependent. In an average-risk, mixed population, the variability in ADR reflects quality of the provider’s endoscopic skills and pathology recognition, rather than the risk of the underlying population.

3. Incidence measure. CMS concluded that Measure 343: Screening Colonoscopy Adenoma Detection Rate is considered an “incidence measure” that does not assess the quality of the care provided. In essence, according to CMS, the measure is based on happenstance rather than the eligible clinician providing a thorough examination.

The societies strongly disagreed with this characterization of ADR. Measure 343: Screening Colonoscopy Adenoma Detection Rate is the only measure that assess the quality of the exam performed by the physician in an average-risk patient with an adequate bowel preparation. Physicians can improve their adenoma detection rate by paying attention to detail, spending more time looking for adenomas, and learning better techniques.

4. Benchmarking. CMS stated that because of the measure construct, benchmarks calculated from this measure are misrepresented and do not align with the MIPS scoring methodology where 100% indicates better clinical care or control. Guidelines and supplemental literature support a performance target for adenoma detection rate of 25% for a mixed sex population (20% in women and 30% in men). CMS determined that Measure 343: Screening Colonoscopy Adenoma Detection Rate may be appropriate for other programs but does not align with the scoring logic within MIPS. When this measure was introduced, according to the agency, it was under the legacy program, Physician Quality Reporting System (PQRS), a pay-for-reporting program that does not have the same scoring implications as MIPS.

The societies reminded CMS that the 25% is the minimum requirement for performance and is not a benchmark. This minimum requirement continues to increase as well. With 25% being the threshold, for every 1% increase in ADR the risk of fatal interval colon cancer decreases by 3%. In one important study by Corley et al, the lowest quintile of ADR was 19% or lower, and was associated with the highest risk of interval colon cancer.⁴

CMS must begin to move beyond traditional approaches toward benchmarking performance where 100% compliance is expected. It was encouraging to see CMS acknowledge that nuances to evaluating scores are needed based on the ability of a measure to accurately identify and capture performance based on the patient population and measure specifications. For example, these adjustments were finalized for the blood pressure and diabetes HbA_1c measures, where the highest number of points will be achieved for anyone scoring 90% or higher. This modification was based on the knowledge that it is not realistic nor in the interest of patients to assume that clinicians will be able to achieve the desired targeted outcome for every patient. The potential for unintended consequences was factored into an assessment of what performance could be considered achievable.

In our view, ADR is a similar example where 100% performance across a clinician’s population of patients is biologically impossible since not every individual who receives a screening colonoscopy will have an adenoma detected. ADR is the best-established colorectal neoplasia-related quality indicator and research demonstrates that high rates are associated with significant reductions in colorectal cancer risk.

CMS must continue to explore alternative strategies toward benchmarking in MIPS to ensure that achievement is fairly assessed, and top performance scores are determined not solely based on peer performance but also based on clinical evidence balanced with minimizing unintended consequences. The MIPS program and its benchmarking and scoring methodologies must continue to innovate to ensure that physicians provide the best possible care to their patients while also accurately and fairly representing and rewarding clinicians’ performance. Continuing to promote a siloed view toward quality will only reduce the relevance of the MIPS program and lead our members to question the integrity and validity of the program.

References

1. Kaminski MF, Regula J, et al. Quality indicators for colonoscopy and the risk of interval cancer. N Engl J Med. 2010;362(19):1795-803.

2. Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143:844-57.

3. Rubin CE, Haggitt RC, Burmer GC, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology. 1992;103:1611-20.

4. Corley D, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-306.

5. Kaminski MF, et al. Increased rate of adenoma detection associates with reduced risk of colorectal cancer and death. Gastroenterology. 2017 Jul;153[1]:98-105. doi: 10.1053/j.gastro.2017.04.006. Epub 2017 Apr 17.

6. ASGE practice guideline: Measuring the quality of endoscopy. Gastrointest Endosc. 2006;58:S1-S38.

7. Rex DK. Colonoscopic withdrawal technique is associated with adenoma miss rate. Gastrointest Endosc. 2000;51:33-6.

8. Barclay RL, et al. Effect of a time-dependent colonoscopic withdrawal protocol on adenoma detection during screening colonoscopy. Clin Gastroenterol Hepatol. 2008;6:1091-8.

9. Shaukat A, et al. Longer withdrawal time is associated with a reduced incidence of interval cancer after screening colonoscopy. Gastroenterology. 2015 Oct;149[4]:952-7

10. Lee S, et al. Am J Gastroenterol. 2016 Jan;111(1):63-9.

11. Jia H, et al. Water exchange method significantly improves adenoma detection rate: A multicenter, randomized controlled trial. Am J Gastroenterol. 2017;112(4):568-76.

12. ASGE. Endoscopes and devices to improve colon polyp detection. GIE 2015;81:1122-9.

13. Ussui V, et al. Am J Gastroenterol. 2015;110:489-96.

14. Kaminski MF, et al. Leadership training to improve adenoma detection rate in screening colonoscopy: a randomized trial. Gut 2016;65:616-24.

15. Shaukat A, et al. Rates of detection of adenoma, sessile serrated adenoma, and advanced adenoma are stable over time and modifiable. Gastroenterology 2018(Feb);156:816-7.

Dr. Adams is a gastroenterologist and assistant professor at the University of Michigan, Ann Arbor; Dr. Leiman is a gastroenterologist and assistant professor of medicine at Duke Health, Durham, N.C.; Dr. Mathews is a gastroenterologist and leader of Clinical Innovation at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, Baltimore.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

Transcatheter aortic valve replacement (TAVR) was not inferior to conventional surgery with respect to death from any cause at 1 year in a new real-world study in patients age 70 years or older with severe symptomatic aortic stenosis at increased operative risk due to age or comorbidity.

The UK TAVI study was presented March 29 at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC).

The trial involved a broad group of patients who were treated at every medical center that performs the transcatheter procedure across the United Kingdom.

“The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting,” said lead author, William D. Toff, MD, professor of cardiology at the University of Leicester, United Kingdom.

Previous clinical trials have found TAVR to be noninferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves, he noted.

“Our results are concordant with those from earlier trials in intermediate- and low-risk patients, but those earlier trials were performed in the best centers and had many exclusion criteria. We have replicated those results in populations more representative of the real world.”

“I think it is a very important message that supports the findings in earlier trials that were focused on showing whether TAVR can work under ideal conditions, while our trial shows that it does work in real-world clinical practice,” he added.

The UK TAVI trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 UK sites from 2014 to 2018. They were randomly assigned to receive TAVR or open-heart surgery.

Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors). The average age was 81 years.

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons (STS) risk score of 2.6%. However, researchers did not specify a particular risk score cutoff for enrollment.

“This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians’ nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach,” Toff said.

At 1 year, the rate of death from any cause (the primary endpoint) was 4.6% in the TAVR group and 6.6% in the surgery group, a difference that met the trial’s prespecified threshold for noninferiority of TAVR.

Rates of death from cardiovascular disease or stroke were also similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications (4.8%) than those receiving surgery (1.3%).

TAVR patients were also more likely to have a pacemaker implanted. This occurred in 12.2% of TAVR patients and 6.6% of those undergoing surgery.

In addition, patients who underwent TAVR had a higher rate of aortic regurgitation. Mild aortic regurgitation occurred at 1 year in 38.3% of the TAVR group and 11.7% of the surgery group, whereas moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of patients having TAVR and 17.1% of those undergoing surgery.

TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and a faster improvement in functional capacity and quality of life. Functional capacity and quality-of-life measures at 6 weeks after the procedure were better in the TAVR group but by 1 year they were similar in the two groups.

“Longer follow-up is required to confirm sustained clinical benefit and valve durability to inform clinical practice, particularly in younger patients,” Toff concluded.

“The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain,” he added.

The researchers plan to continue to track outcomes for a minimum of 5 years.

Discussant of the UK TAVI trial at an ACC press conference, Julia Grapsa, MD, Guys and St Thomas NHS Trust, London, United Kingdom, said it was a well-designed study.

“It was impressive to see so many UK sites and the age range of patients from 70 to 91 years, and the shorter hospital stays and functional recoveries as well as reduced major bleeding in the TAVR group,” Grapsa said.

“But something that was very striking to me was the increase in moderate aortic regurgitation in the TAVR arm, 2.3% versus 0.6% in the surgical arm, so it is very important to keep following these patients long term,” she added.

In answer to a question during the main session about using age alone as an inclusion criterion in those over 80 years old, Toff said, “We were more comfortable taking all comers over 80 years of age because of the uncertainty about TAVR is more in relation to its durability and the clinical significance of the aortic regurgitation, which may have consequences in the longer term. But the longer term for the over 80s is obviously less of a problem than for those in their 70s.”

This study was funded by the UK National Institute for Health Research Health Technology Assessment Programme. Toff reports no disclosures.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Abstract 20-LB-20410-ACC. Presented March 29, 2020.

This article first appeared on Medscape.com.

In a small study, a self-administered vaginal insert containing the antimalarial agent artesunate resolved cervical intraepithelial neoplasia (CIN) 2/3 lesions in two-thirds of patients and cleared human papillomavirus (HPV) genotypes in nearly half of women whose lesions disappeared.

Ying Liu, Shanghai Xinhua News Agency

Among 28 women with biopsy-confirmed CIN 2/3 who used the inserts prior to a planned standard-of-care resection, histologic regression of lesions occurred in 19 patients. In 9 of the 19 women, there was clearance of baseline HPV genotypes.

These results were reported in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The study results were also published in Gynecologic Oncology.

An unexpected treatment

“The implications of having a safe, inexpensive, self-administered, shelf-stable, nonsurgical treatment for HPV intraepithelial disease, not only here in the U.S., but also extending to low-resource settings,” are self-evident, said study author Cornelia L. Trimble, MD, of Johns Hopkins University in Baltimore.

“This could change the entire landscape of care,” Dr. Trimble said in an interview. “Who’d have thunk that a freaking Chinese herbal medicine derived from the bark of a tree could have this effect?”

Artesunate is a derivative of artemisinin, an antimalarial isolated from the plant Artemisia annua, which is used in traditional Chinese medicine. According to the Centers for Disease Control and Prevention, intravenous artesunate is the first-line drug for treatment of severe malaria in the United States.

However, artesunate is neither approved by the Food and Drug Administration nor commercially available in the United States. The CDC provides artesunate to U.S. clinicians on an as-needed basis.

In addition to its antimalarial activity, artesunate has been shown to have a cytotoxic effect on squamous cells transformed by HPV in vitro. Dr. Trimble and colleagues are also testing a topical form of the drug for the treatment of vulvar intraepithelial neoplasia.

Patients, dosing, and efficacy

In the current study, Dr. Trimble and colleagues enrolled adult immunocompetent women with CIN 2/3, visible residual lesions, and detectable HPV. The patients were assigned sequentially to one of four treatment groups: one 5-day cycle of 50-mg inserts or one, two, or three 5-day cycles using 200-mg inserts.

The patients were instructed to place the inserts at bedtime using a vaginal applicator, followed by a tampon, and then remove the inserts in the morning.

In a modified intention-to-treat analysis including all women who received at least one dose of artesunate and who had endpoint data available, 19 of 28 (67.9%) had histologic regression of CIN lesions. Of the 19 patients, 9 (47.4%) had clearance of all HPV genotypes that had been present at baseline.

Asked how the investigators could distinguish between the treatment effect of the inserts and spontaneous clearance of lesions seen as part of the natural history of CIN in some patients, Dr. Trimble pointed to two observations suggesting an immunologic effect from treatment.

Specifically, although there was lesion regression to CIN 1 or less in all treatment groups, the patients who had only a single treatment cycle had a longer time to regression than those who received two or three cycles.

Additionally, among the nine patients who had viral clearance, three had clearance at the same study time point where histologic regression was observed. For the other six patients, the virus did not clear until several weeks following lesion regression.

These two observations suggest the therapeutic effect of artesunate is recognized by the immune system, which may stimulate a localized immune-mediated cytotoxic effect, Dr. Trimble said.

Safety and next steps

The safety analysis showed that side effects were generally mild and well tolerated. There were 161 adverse events among 29 women for whom safety data were available. The most frequently reported adverse events were vaginal itching (n = 13), vaginal pain (n = 12), vaginal discharge (n = 8), spotting (n = 6), uterine cramping (n = 6), vaginal dryness (n = 4), pelvic pain (n = 1), perineal pain (n = 1), and dyspareunia (n = 1).

Grade 2 adverse events included vaginal yeast infection (n = 6), bacterial vaginosis (n = 2), vaginal inflammation (n = 2), urinary tract infection (n = 2), and noninfective cystitis (n = 1). There were no grade 3 or 4 adverse events reported, and three women reported no noticeable side effects.

Dr. Trimble and colleagues are continuing to study immune responses in cervical tissues and are examining the composition and functions of the cervicovaginal metagenome, looking at bacterial, viral, and fungal components. The team has joined with collaborators at the University of Texas MD Anderson Cancer Center in Houston to look for immune markers in longitudinally collected, subject-matched cervical swabs.

Frantz Viral Therapeutics supplied the artesunate vaginal inserts and partial financial support for this study. Dr. Trimble disclosed relationships with a range of companies and organizations outside this work.

SOURCE: Trimble C L et al. SGO 2020, Abstract LBA 1.

In a small study, a self-administered vaginal insert containing the antimalarial agent artesunate resolved cervical intraepithelial neoplasia (CIN) 2/3 lesions in two-thirds of patients and cleared human papillomavirus (HPV) genotypes in nearly half of women whose lesions disappeared.

Ying Liu, Shanghai Xinhua News Agency

Among 28 women with biopsy-confirmed CIN 2/3 who used the inserts prior to a planned standard-of-care resection, histologic regression of lesions occurred in 19 patients. In 9 of the 19 women, there was clearance of baseline HPV genotypes.

These results were reported in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The study results were also published in Gynecologic Oncology.

An unexpected treatment

“The implications of having a safe, inexpensive, self-administered, shelf-stable, nonsurgical treatment for HPV intraepithelial disease, not only here in the U.S., but also extending to low-resource settings,” are self-evident, said study author Cornelia L. Trimble, MD, of Johns Hopkins University in Baltimore.

“This could change the entire landscape of care,” Dr. Trimble said in an interview. “Who’d have thunk that a freaking Chinese herbal medicine derived from the bark of a tree could have this effect?”

Artesunate is a derivative of artemisinin, an antimalarial isolated from the plant Artemisia annua, which is used in traditional Chinese medicine. According to the Centers for Disease Control and Prevention, intravenous artesunate is the first-line drug for treatment of severe malaria in the United States.

However, artesunate is neither approved by the Food and Drug Administration nor commercially available in the United States. The CDC provides artesunate to U.S. clinicians on an as-needed basis.

In addition to its antimalarial activity, artesunate has been shown to have a cytotoxic effect on squamous cells transformed by HPV in vitro. Dr. Trimble and colleagues are also testing a topical form of the drug for the treatment of vulvar intraepithelial neoplasia.

Patients, dosing, and efficacy

In the current study, Dr. Trimble and colleagues enrolled adult immunocompetent women with CIN 2/3, visible residual lesions, and detectable HPV. The patients were assigned sequentially to one of four treatment groups: one 5-day cycle of 50-mg inserts or one, two, or three 5-day cycles using 200-mg inserts.

The patients were instructed to place the inserts at bedtime using a vaginal applicator, followed by a tampon, and then remove the inserts in the morning.

In a modified intention-to-treat analysis including all women who received at least one dose of artesunate and who had endpoint data available, 19 of 28 (67.9%) had histologic regression of CIN lesions. Of the 19 patients, 9 (47.4%) had clearance of all HPV genotypes that had been present at baseline.

Asked how the investigators could distinguish between the treatment effect of the inserts and spontaneous clearance of lesions seen as part of the natural history of CIN in some patients, Dr. Trimble pointed to two observations suggesting an immunologic effect from treatment.

Specifically, although there was lesion regression to CIN 1 or less in all treatment groups, the patients who had only a single treatment cycle had a longer time to regression than those who received two or three cycles.

Additionally, among the nine patients who had viral clearance, three had clearance at the same study time point where histologic regression was observed. For the other six patients, the virus did not clear until several weeks following lesion regression.

These two observations suggest the therapeutic effect of artesunate is recognized by the immune system, which may stimulate a localized immune-mediated cytotoxic effect, Dr. Trimble said.

Safety and next steps

The safety analysis showed that side effects were generally mild and well tolerated. There were 161 adverse events among 29 women for whom safety data were available. The most frequently reported adverse events were vaginal itching (n = 13), vaginal pain (n = 12), vaginal discharge (n = 8), spotting (n = 6), uterine cramping (n = 6), vaginal dryness (n = 4), pelvic pain (n = 1), perineal pain (n = 1), and dyspareunia (n = 1).

Grade 2 adverse events included vaginal yeast infection (n = 6), bacterial vaginosis (n = 2), vaginal inflammation (n = 2), urinary tract infection (n = 2), and noninfective cystitis (n = 1). There were no grade 3 or 4 adverse events reported, and three women reported no noticeable side effects.

Dr. Trimble and colleagues are continuing to study immune responses in cervical tissues and are examining the composition and functions of the cervicovaginal metagenome, looking at bacterial, viral, and fungal components. The team has joined with collaborators at the University of Texas MD Anderson Cancer Center in Houston to look for immune markers in longitudinally collected, subject-matched cervical swabs.

Frantz Viral Therapeutics supplied the artesunate vaginal inserts and partial financial support for this study. Dr. Trimble disclosed relationships with a range of companies and organizations outside this work.

SOURCE: Trimble C L et al. SGO 2020, Abstract LBA 1.

In a small study, a self-administered vaginal insert containing the antimalarial agent artesunate resolved cervical intraepithelial neoplasia (CIN) 2/3 lesions in two-thirds of patients and cleared human papillomavirus (HPV) genotypes in nearly half of women whose lesions disappeared.

Ying Liu, Shanghai Xinhua News Agency

Among 28 women with biopsy-confirmed CIN 2/3 who used the inserts prior to a planned standard-of-care resection, histologic regression of lesions occurred in 19 patients. In 9 of the 19 women, there was clearance of baseline HPV genotypes.

These results were reported in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The study results were also published in Gynecologic Oncology.

An unexpected treatment

“The implications of having a safe, inexpensive, self-administered, shelf-stable, nonsurgical treatment for HPV intraepithelial disease, not only here in the U.S., but also extending to low-resource settings,” are self-evident, said study author Cornelia L. Trimble, MD, of Johns Hopkins University in Baltimore.

“This could change the entire landscape of care,” Dr. Trimble said in an interview. “Who’d have thunk that a freaking Chinese herbal medicine derived from the bark of a tree could have this effect?”

Artesunate is a derivative of artemisinin, an antimalarial isolated from the plant Artemisia annua, which is used in traditional Chinese medicine. According to the Centers for Disease Control and Prevention, intravenous artesunate is the first-line drug for treatment of severe malaria in the United States.

However, artesunate is neither approved by the Food and Drug Administration nor commercially available in the United States. The CDC provides artesunate to U.S. clinicians on an as-needed basis.

In addition to its antimalarial activity, artesunate has been shown to have a cytotoxic effect on squamous cells transformed by HPV in vitro. Dr. Trimble and colleagues are also testing a topical form of the drug for the treatment of vulvar intraepithelial neoplasia.

Patients, dosing, and efficacy

In the current study, Dr. Trimble and colleagues enrolled adult immunocompetent women with CIN 2/3, visible residual lesions, and detectable HPV. The patients were assigned sequentially to one of four treatment groups: one 5-day cycle of 50-mg inserts or one, two, or three 5-day cycles using 200-mg inserts.

The patients were instructed to place the inserts at bedtime using a vaginal applicator, followed by a tampon, and then remove the inserts in the morning.

In a modified intention-to-treat analysis including all women who received at least one dose of artesunate and who had endpoint data available, 19 of 28 (67.9%) had histologic regression of CIN lesions. Of the 19 patients, 9 (47.4%) had clearance of all HPV genotypes that had been present at baseline.

Asked how the investigators could distinguish between the treatment effect of the inserts and spontaneous clearance of lesions seen as part of the natural history of CIN in some patients, Dr. Trimble pointed to two observations suggesting an immunologic effect from treatment.

Specifically, although there was lesion regression to CIN 1 or less in all treatment groups, the patients who had only a single treatment cycle had a longer time to regression than those who received two or three cycles.

Additionally, among the nine patients who had viral clearance, three had clearance at the same study time point where histologic regression was observed. For the other six patients, the virus did not clear until several weeks following lesion regression.

These two observations suggest the therapeutic effect of artesunate is recognized by the immune system, which may stimulate a localized immune-mediated cytotoxic effect, Dr. Trimble said.

Safety and next steps

The safety analysis showed that side effects were generally mild and well tolerated. There were 161 adverse events among 29 women for whom safety data were available. The most frequently reported adverse events were vaginal itching (n = 13), vaginal pain (n = 12), vaginal discharge (n = 8), spotting (n = 6), uterine cramping (n = 6), vaginal dryness (n = 4), pelvic pain (n = 1), perineal pain (n = 1), and dyspareunia (n = 1).

Grade 2 adverse events included vaginal yeast infection (n = 6), bacterial vaginosis (n = 2), vaginal inflammation (n = 2), urinary tract infection (n = 2), and noninfective cystitis (n = 1). There were no grade 3 or 4 adverse events reported, and three women reported no noticeable side effects.

Dr. Trimble and colleagues are continuing to study immune responses in cervical tissues and are examining the composition and functions of the cervicovaginal metagenome, looking at bacterial, viral, and fungal components. The team has joined with collaborators at the University of Texas MD Anderson Cancer Center in Houston to look for immune markers in longitudinally collected, subject-matched cervical swabs.

Frantz Viral Therapeutics supplied the artesunate vaginal inserts and partial financial support for this study. Dr. Trimble disclosed relationships with a range of companies and organizations outside this work.

SOURCE: Trimble C L et al. SGO 2020, Abstract LBA 1.

Documentation of gender-based disparities in medicine often focus on lower numbers of women in prominent positions as evidence of inequality and inequity; examples include lower proportion of women physicians as conference speakers,¹ first and last authors of manuscripts,² invited editorials,³ award recipients,⁴ grant recipients,⁵ medical society leadership,⁶ editorial boards,⁷ and presenters at grand rounds.⁸ Notably, these disparities are likely greater for intersectional physicians, who experience bias through multiple lenses of disadvantage.⁹ While the scarcity of women and marginalized populations in leadership roles in medicine provides convincing evidence that inequality exists, the underrepresentation of women and other marginalized physicians in prominent positions is also a cause of continued disparity. Fewer academic opportunities for women physicians and other underrepresented physician groups in medicine may perpetuate slower career advancement¹⁰ and contribute to less availability of mentors and sponsors.¹¹ Less obviously, underrepresentation also unintentionally and explicitly signals to junior faculty from marginalized groups that they are not welcome and are unlikely to be successful.^9,12

Improving representation of women in other fields has been demonstrated to reduce implicit and explicit sexism.^13,14 Increasing diversity in academic leadership is likely to further improve diversity at all levels,^9,15 which may in turn reduce gaps in health outcomes seen for marginalized patients.^16-18 Measuring and eliminating bias that disadvantages underrepresented physicians in academic opportunities is a moral imperative for institutions and organizations. For this reason, the Society of Hospital Medicine (SHM) has been attempting to address this issue within its organizational structure, publications, and conference presenters.¹⁹

The first step for an organization that aims to increase representation of women and other marginalized groups in medicine is to assess the current representation of leadership and opportunities.²⁰ If data are available, this review should include intersectional measurement of other axes of discrimination. Rapid analysis of large data sets of names is feasible using freely available computer algorithms, for example.²¹ Only once a baseline understanding of representation within an organization is established can identification of goals and areas of improvement and evaluation of efforts to increase representation begin. Reporting this data to the organization’s membership should be undertaken to increase the accountability of leadership to reduce gaps. This work is currently underway at the Journal of Hospital Medicine and within the Society of Hospital Medicine.¹⁹

This month’s issue of the Journal of Hospital Medicine includes an article written by Northcutt, et al that describes one such attempt, focusing on representation of conference speakers at SHM’s Annual Meeting. In this study, authors performed a pre- and postintervention analysis of an open call system for selecting didactic speakers for the SHM Annual Meeting. The open call system, implemented for the 2019 SHM Annual Meeting, invited all members to apply for a didactic session. The planning committee then utilized a standardized evaluation form to determine the final speaker list. In previous years, didactic speakers did not apply but were invited and were not formally evaluated. Northcutt et al report that this intervention was associated with a significant increase in the proportion of women conference speakers.²²

The Northcutt article and the open call and evaluation system is one example of an intentional adjustment to the speaker selection process aimed at recruiting more diverse presenters. Other examples of intentional efforts to increase diversity within conferences include using curated lists designed to improve representation or contacting other national organizations for recommendations. ²⁰ Efforts such as these are necessary because men in medicine are more likely to volunteer for prominent positions than women,²³ meaning that any system of recruitment or allocation of academic opportunities that relies on self-promotion is likely to perpetuate underrepresentation. Using pre-existing speakers list or previous programs will also support ongoing disparities, because men have traditionally represented the majority of speakers.

Of course, conferences are an important and public representation of a society, but are only the starting point for working towards equity within a large organization such as SHM. Similar efforts must be directed towards authorship in SHM publications, representation on editorial boards, society leadership and employment opportunities. Once organizations have an established baseline around publications, leadership recruitment, and employment representation, a review of recruitment policies (for articles, speakers, leaders, and employees) should then be conducted, looking for areas that lead to bias.

Planning committees, editorial boards, and society leadership groups should also intentionally increase their own diversity, as increasing the proportion of women on a convening committee has been demonstrated to increase the number of invited women speakers.^15,24 In addition, committees can adopt a mandate to increase diversity in invited speakers, editorials, and authorship; for example, direct instruction to avoid all-male panels led a conference planning committee to invite more women and increased the numbers of women speakers.²⁵ A speaker, authorship, or editorial policy that emphasizes diversity and inclusion should be developed and made available to the organization’s membership.²⁶

Finally, there is evidence that implicit bias training for editorial boards and conference planning committees may be effective.²⁷ Implicit bias training emphasizes that judgements of merit and skill are often subjective and based on in-group membership rather than the quality of applicants.⁹ For example, underrepresentation of women at a neuroimmunology conference was not explained by quantity or impact of previous publications,²⁸ and evaluation scores for the Society for Hospital Medicine’s Annual Meeting have increased as the proportion of women speakers has increased, suggesting that the presence of women presenters was associated with better presentations. To address concerns about how diversity and inclusion efforts may influence the quality of speakers and authors,²⁹ objective criteria could be developed in advance of a selection process and candidates should be held to the same standard.³⁰ The use of objective evaluation criteria in the selection of conference speakers has also been associated with increasing the proportion of women conference speakers. All in all, SHM’s efforts (and Northcutt’s work) should be lauded but also recognized as what they are: a good start. Continued vigilance focused on equity is the only way to ensure that the move towards greater representation continues.

Documentation of gender-based disparities in medicine often focus on lower numbers of women in prominent positions as evidence of inequality and inequity; examples include lower proportion of women physicians as conference speakers,¹ first and last authors of manuscripts,² invited editorials,³ award recipients,⁴ grant recipients,⁵ medical society leadership,⁶ editorial boards,⁷ and presenters at grand rounds.⁸ Notably, these disparities are likely greater for intersectional physicians, who experience bias through multiple lenses of disadvantage.⁹ While the scarcity of women and marginalized populations in leadership roles in medicine provides convincing evidence that inequality exists, the underrepresentation of women and other marginalized physicians in prominent positions is also a cause of continued disparity. Fewer academic opportunities for women physicians and other underrepresented physician groups in medicine may perpetuate slower career advancement¹⁰ and contribute to less availability of mentors and sponsors.¹¹ Less obviously, underrepresentation also unintentionally and explicitly signals to junior faculty from marginalized groups that they are not welcome and are unlikely to be successful.^9,12

Improving representation of women in other fields has been demonstrated to reduce implicit and explicit sexism.^13,14 Increasing diversity in academic leadership is likely to further improve diversity at all levels,^9,15 which may in turn reduce gaps in health outcomes seen for marginalized patients.^16-18 Measuring and eliminating bias that disadvantages underrepresented physicians in academic opportunities is a moral imperative for institutions and organizations. For this reason, the Society of Hospital Medicine (SHM) has been attempting to address this issue within its organizational structure, publications, and conference presenters.¹⁹

The first step for an organization that aims to increase representation of women and other marginalized groups in medicine is to assess the current representation of leadership and opportunities.²⁰ If data are available, this review should include intersectional measurement of other axes of discrimination. Rapid analysis of large data sets of names is feasible using freely available computer algorithms, for example.²¹ Only once a baseline understanding of representation within an organization is established can identification of goals and areas of improvement and evaluation of efforts to increase representation begin. Reporting this data to the organization’s membership should be undertaken to increase the accountability of leadership to reduce gaps. This work is currently underway at the Journal of Hospital Medicine and within the Society of Hospital Medicine.¹⁹

This month’s issue of the Journal of Hospital Medicine includes an article written by Northcutt, et al that describes one such attempt, focusing on representation of conference speakers at SHM’s Annual Meeting. In this study, authors performed a pre- and postintervention analysis of an open call system for selecting didactic speakers for the SHM Annual Meeting. The open call system, implemented for the 2019 SHM Annual Meeting, invited all members to apply for a didactic session. The planning committee then utilized a standardized evaluation form to determine the final speaker list. In previous years, didactic speakers did not apply but were invited and were not formally evaluated. Northcutt et al report that this intervention was associated with a significant increase in the proportion of women conference speakers.²²

The Northcutt article and the open call and evaluation system is one example of an intentional adjustment to the speaker selection process aimed at recruiting more diverse presenters. Other examples of intentional efforts to increase diversity within conferences include using curated lists designed to improve representation or contacting other national organizations for recommendations. ²⁰ Efforts such as these are necessary because men in medicine are more likely to volunteer for prominent positions than women,²³ meaning that any system of recruitment or allocation of academic opportunities that relies on self-promotion is likely to perpetuate underrepresentation. Using pre-existing speakers list or previous programs will also support ongoing disparities, because men have traditionally represented the majority of speakers.

Of course, conferences are an important and public representation of a society, but are only the starting point for working towards equity within a large organization such as SHM. Similar efforts must be directed towards authorship in SHM publications, representation on editorial boards, society leadership and employment opportunities. Once organizations have an established baseline around publications, leadership recruitment, and employment representation, a review of recruitment policies (for articles, speakers, leaders, and employees) should then be conducted, looking for areas that lead to bias.

Planning committees, editorial boards, and society leadership groups should also intentionally increase their own diversity, as increasing the proportion of women on a convening committee has been demonstrated to increase the number of invited women speakers.^15,24 In addition, committees can adopt a mandate to increase diversity in invited speakers, editorials, and authorship; for example, direct instruction to avoid all-male panels led a conference planning committee to invite more women and increased the numbers of women speakers.²⁵ A speaker, authorship, or editorial policy that emphasizes diversity and inclusion should be developed and made available to the organization’s membership.²⁶

Finally, there is evidence that implicit bias training for editorial boards and conference planning committees may be effective.²⁷ Implicit bias training emphasizes that judgements of merit and skill are often subjective and based on in-group membership rather than the quality of applicants.⁹ For example, underrepresentation of women at a neuroimmunology conference was not explained by quantity or impact of previous publications,²⁸ and evaluation scores for the Society for Hospital Medicine’s Annual Meeting have increased as the proportion of women speakers has increased, suggesting that the presence of women presenters was associated with better presentations. To address concerns about how diversity and inclusion efforts may influence the quality of speakers and authors,²⁹ objective criteria could be developed in advance of a selection process and candidates should be held to the same standard.³⁰ The use of objective evaluation criteria in the selection of conference speakers has also been associated with increasing the proportion of women conference speakers. All in all, SHM’s efforts (and Northcutt’s work) should be lauded but also recognized as what they are: a good start. Continued vigilance focused on equity is the only way to ensure that the move towards greater representation continues.

Documentation of gender-based disparities in medicine often focus on lower numbers of women in prominent positions as evidence of inequality and inequity; examples include lower proportion of women physicians as conference speakers,¹ first and last authors of manuscripts,² invited editorials,³ award recipients,⁴ grant recipients,⁵ medical society leadership,⁶ editorial boards,⁷ and presenters at grand rounds.⁸ Notably, these disparities are likely greater for intersectional physicians, who experience bias through multiple lenses of disadvantage.⁹ While the scarcity of women and marginalized populations in leadership roles in medicine provides convincing evidence that inequality exists, the underrepresentation of women and other marginalized physicians in prominent positions is also a cause of continued disparity. Fewer academic opportunities for women physicians and other underrepresented physician groups in medicine may perpetuate slower career advancement¹⁰ and contribute to less availability of mentors and sponsors.¹¹ Less obviously, underrepresentation also unintentionally and explicitly signals to junior faculty from marginalized groups that they are not welcome and are unlikely to be successful.^9,12

Improving representation of women in other fields has been demonstrated to reduce implicit and explicit sexism.^13,14 Increasing diversity in academic leadership is likely to further improve diversity at all levels,^9,15 which may in turn reduce gaps in health outcomes seen for marginalized patients.^16-18 Measuring and eliminating bias that disadvantages underrepresented physicians in academic opportunities is a moral imperative for institutions and organizations. For this reason, the Society of Hospital Medicine (SHM) has been attempting to address this issue within its organizational structure, publications, and conference presenters.¹⁹

The first step for an organization that aims to increase representation of women and other marginalized groups in medicine is to assess the current representation of leadership and opportunities.²⁰ If data are available, this review should include intersectional measurement of other axes of discrimination. Rapid analysis of large data sets of names is feasible using freely available computer algorithms, for example.²¹ Only once a baseline understanding of representation within an organization is established can identification of goals and areas of improvement and evaluation of efforts to increase representation begin. Reporting this data to the organization’s membership should be undertaken to increase the accountability of leadership to reduce gaps. This work is currently underway at the Journal of Hospital Medicine and within the Society of Hospital Medicine.¹⁹

This month’s issue of the Journal of Hospital Medicine includes an article written by Northcutt, et al that describes one such attempt, focusing on representation of conference speakers at SHM’s Annual Meeting. In this study, authors performed a pre- and postintervention analysis of an open call system for selecting didactic speakers for the SHM Annual Meeting. The open call system, implemented for the 2019 SHM Annual Meeting, invited all members to apply for a didactic session. The planning committee then utilized a standardized evaluation form to determine the final speaker list. In previous years, didactic speakers did not apply but were invited and were not formally evaluated. Northcutt et al report that this intervention was associated with a significant increase in the proportion of women conference speakers.²²

The Northcutt article and the open call and evaluation system is one example of an intentional adjustment to the speaker selection process aimed at recruiting more diverse presenters. Other examples of intentional efforts to increase diversity within conferences include using curated lists designed to improve representation or contacting other national organizations for recommendations. ²⁰ Efforts such as these are necessary because men in medicine are more likely to volunteer for prominent positions than women,²³ meaning that any system of recruitment or allocation of academic opportunities that relies on self-promotion is likely to perpetuate underrepresentation. Using pre-existing speakers list or previous programs will also support ongoing disparities, because men have traditionally represented the majority of speakers.

Of course, conferences are an important and public representation of a society, but are only the starting point for working towards equity within a large organization such as SHM. Similar efforts must be directed towards authorship in SHM publications, representation on editorial boards, society leadership and employment opportunities. Once organizations have an established baseline around publications, leadership recruitment, and employment representation, a review of recruitment policies (for articles, speakers, leaders, and employees) should then be conducted, looking for areas that lead to bias.

Planning committees, editorial boards, and society leadership groups should also intentionally increase their own diversity, as increasing the proportion of women on a convening committee has been demonstrated to increase the number of invited women speakers.^15,24 In addition, committees can adopt a mandate to increase diversity in invited speakers, editorials, and authorship; for example, direct instruction to avoid all-male panels led a conference planning committee to invite more women and increased the numbers of women speakers.²⁵ A speaker, authorship, or editorial policy that emphasizes diversity and inclusion should be developed and made available to the organization’s membership.²⁶

Finally, there is evidence that implicit bias training for editorial boards and conference planning committees may be effective.²⁷ Implicit bias training emphasizes that judgements of merit and skill are often subjective and based on in-group membership rather than the quality of applicants.⁹ For example, underrepresentation of women at a neuroimmunology conference was not explained by quantity or impact of previous publications,²⁸ and evaluation scores for the Society for Hospital Medicine’s Annual Meeting have increased as the proportion of women speakers has increased, suggesting that the presence of women presenters was associated with better presentations. To address concerns about how diversity and inclusion efforts may influence the quality of speakers and authors,²⁹ objective criteria could be developed in advance of a selection process and candidates should be held to the same standard.³⁰ The use of objective evaluation criteria in the selection of conference speakers has also been associated with increasing the proportion of women conference speakers. All in all, SHM’s efforts (and Northcutt’s work) should be lauded but also recognized as what they are: a good start. Continued vigilance focused on equity is the only way to ensure that the move towards greater representation continues.

“Without meeting leadership skills, one joins the ranks of so many others who bear the responsibility for the meeting ‘problem’ and are the cause of so much frustration in the workplace.”¹ Physicians, like so many others, often feel that team meetings are inefficient, a waste of time, and mentally draining. It does not have to be this way. There are evidence-based strategies that can make meetings truly work and actually enjoyable to attend.² This is particularly important because eliminating meetings is a false solution. Hospitals need team meetings to promote coordination, collaboration, communication, and consensus decision-making. While no one individual can solve the meetings problem, each of us can find a meeting we lead and make it work better.

First, recognize that, as a leader, you are a steward of others’ time. As a steward, be intentional when designing meetings. Think carefully about who needs to be there, how much time to spend on the meeting, and how the meeting should be run. Dysfunction increases with meeting size, so invite attendees wisely; include only those essential to the meeting. For individuals not in the core group, offer them the opportunity to share their input premeeting if desired, share good meeting minutes with them, and welcome them to attend future meetings if desired. Consider “representative voices”—openly asking certain attendees to represent a group of stakeholders. Use a timed agenda to invite certain people for part, but not all, of the meeting.

Keep your meetings lean and deliberate. Avoid defaulting to one-hour meetings out of habit. Parkinson’s Law suggests that people will fill the time allotted to a particular task. If a meeting can be done in 30 minutes but is scheduled for 60 minutes, chances are that people will use the full hour. If a decision is reached faster than anticipated, end the meeting early. Refer back to your steward mindset and schedule meeting time with intention.

Meetings are often experienced psychologically like we experience interruptions. Thus, when attendees arrive at a meeting, express gratitude. Your job is to keep attendees active and engaged; therefore, facilitate the meeting actively and creatively. Try out different techniques such as devoting a few minutes to silent, written brainstorming. Leveraging silence gives attendees the opportunity to think on their own before contributing to the discussion and results in nearly twice the number of ideas.³ Perhaps members can be assigned explicit roles such as devil’s advocate, or each attendee can be assigned a specific agenda item, invoking responsibility and participation. If you always sit during meetings, try standing. If you have never tried a walking meeting, give it a go. Attendees appreciate mixing things up.

Lastly, remember to check-in with attendees to see how things are going. Never get too comfortable as a meeting leader, especially since meeting frustration abounds. Asking your team for feedback will carry over to other aspects of your role. You will be seen as a conscientious leader, open to exploration and professional development. This builds trust and creates a positive, collaborative work environment.

While you cannot control how others run their meetings, you do have the ability to make a meeting that you lead truly work. Be intentional with your role as a meeting facilitator and focus on the whole experience. Evaluate and learn from your team, show others that you care about your meetings so that they begin to care about theirs too.

“Without meeting leadership skills, one joins the ranks of so many others who bear the responsibility for the meeting ‘problem’ and are the cause of so much frustration in the workplace.”¹ Physicians, like so many others, often feel that team meetings are inefficient, a waste of time, and mentally draining. It does not have to be this way. There are evidence-based strategies that can make meetings truly work and actually enjoyable to attend.² This is particularly important because eliminating meetings is a false solution. Hospitals need team meetings to promote coordination, collaboration, communication, and consensus decision-making. While no one individual can solve the meetings problem, each of us can find a meeting we lead and make it work better.

First, recognize that, as a leader, you are a steward of others’ time. As a steward, be intentional when designing meetings. Think carefully about who needs to be there, how much time to spend on the meeting, and how the meeting should be run. Dysfunction increases with meeting size, so invite attendees wisely; include only those essential to the meeting. For individuals not in the core group, offer them the opportunity to share their input premeeting if desired, share good meeting minutes with them, and welcome them to attend future meetings if desired. Consider “representative voices”—openly asking certain attendees to represent a group of stakeholders. Use a timed agenda to invite certain people for part, but not all, of the meeting.

Keep your meetings lean and deliberate. Avoid defaulting to one-hour meetings out of habit. Parkinson’s Law suggests that people will fill the time allotted to a particular task. If a meeting can be done in 30 minutes but is scheduled for 60 minutes, chances are that people will use the full hour. If a decision is reached faster than anticipated, end the meeting early. Refer back to your steward mindset and schedule meeting time with intention.

Meetings are often experienced psychologically like we experience interruptions. Thus, when attendees arrive at a meeting, express gratitude. Your job is to keep attendees active and engaged; therefore, facilitate the meeting actively and creatively. Try out different techniques such as devoting a few minutes to silent, written brainstorming. Leveraging silence gives attendees the opportunity to think on their own before contributing to the discussion and results in nearly twice the number of ideas.³ Perhaps members can be assigned explicit roles such as devil’s advocate, or each attendee can be assigned a specific agenda item, invoking responsibility and participation. If you always sit during meetings, try standing. If you have never tried a walking meeting, give it a go. Attendees appreciate mixing things up.

Lastly, remember to check-in with attendees to see how things are going. Never get too comfortable as a meeting leader, especially since meeting frustration abounds. Asking your team for feedback will carry over to other aspects of your role. You will be seen as a conscientious leader, open to exploration and professional development. This builds trust and creates a positive, collaborative work environment.

While you cannot control how others run their meetings, you do have the ability to make a meeting that you lead truly work. Be intentional with your role as a meeting facilitator and focus on the whole experience. Evaluate and learn from your team, show others that you care about your meetings so that they begin to care about theirs too.

“Without meeting leadership skills, one joins the ranks of so many others who bear the responsibility for the meeting ‘problem’ and are the cause of so much frustration in the workplace.”¹ Physicians, like so many others, often feel that team meetings are inefficient, a waste of time, and mentally draining. It does not have to be this way. There are evidence-based strategies that can make meetings truly work and actually enjoyable to attend.² This is particularly important because eliminating meetings is a false solution. Hospitals need team meetings to promote coordination, collaboration, communication, and consensus decision-making. While no one individual can solve the meetings problem, each of us can find a meeting we lead and make it work better.

First, recognize that, as a leader, you are a steward of others’ time. As a steward, be intentional when designing meetings. Think carefully about who needs to be there, how much time to spend on the meeting, and how the meeting should be run. Dysfunction increases with meeting size, so invite attendees wisely; include only those essential to the meeting. For individuals not in the core group, offer them the opportunity to share their input premeeting if desired, share good meeting minutes with them, and welcome them to attend future meetings if desired. Consider “representative voices”—openly asking certain attendees to represent a group of stakeholders. Use a timed agenda to invite certain people for part, but not all, of the meeting.

Keep your meetings lean and deliberate. Avoid defaulting to one-hour meetings out of habit. Parkinson’s Law suggests that people will fill the time allotted to a particular task. If a meeting can be done in 30 minutes but is scheduled for 60 minutes, chances are that people will use the full hour. If a decision is reached faster than anticipated, end the meeting early. Refer back to your steward mindset and schedule meeting time with intention.

Meetings are often experienced psychologically like we experience interruptions. Thus, when attendees arrive at a meeting, express gratitude. Your job is to keep attendees active and engaged; therefore, facilitate the meeting actively and creatively. Try out different techniques such as devoting a few minutes to silent, written brainstorming. Leveraging silence gives attendees the opportunity to think on their own before contributing to the discussion and results in nearly twice the number of ideas.³ Perhaps members can be assigned explicit roles such as devil’s advocate, or each attendee can be assigned a specific agenda item, invoking responsibility and participation. If you always sit during meetings, try standing. If you have never tried a walking meeting, give it a go. Attendees appreciate mixing things up.

Lastly, remember to check-in with attendees to see how things are going. Never get too comfortable as a meeting leader, especially since meeting frustration abounds. Asking your team for feedback will carry over to other aspects of your role. You will be seen as a conscientious leader, open to exploration and professional development. This builds trust and creates a positive, collaborative work environment.

While you cannot control how others run their meetings, you do have the ability to make a meeting that you lead truly work. Be intentional with your role as a meeting facilitator and focus on the whole experience. Evaluate and learn from your team, show others that you care about your meetings so that they begin to care about theirs too.

Persistent gender disparities exist in pay,^1,2 leadership opportunities,^3,4 promotion,⁵ and speaking opportunities.⁶ While the gender distribution of the hospitalist workforce may be approaching parity,^3,7,8 gender differences in leadership, speakership, and authorship have already been noted in hospital medicine.³ Between 2006 and 2012, women constituted less than a third (26%) of the presenters at the national conferences of the Society of Hospital Medicine (SHM) and the Society of General Internal Medicine (SGIM).³

The SHM Annual Meeting has historically had an “open call” peer review process for workshop presenters with the goal of increasing the diversity of presenters. In 2019, this process was expanded to include didactic speakers. Our aim in this study was to assess whether these open call procedures resulted in improved representation of women speakers and how the proportion of women speakers affects the overall evaluation scores of the conference. Our hypothesis was that the introduction of an open call process for the SHM conference didactic speakers would be associated with an increased proportion of women speakers, compared with the closed call processes, without a negative impact on conference scores.

The study is a retrospective evaluation of data collected regarding speakers at the annual SHM conference from 2015 to 2019. The SHM national conference typically has two main types of offerings: workshops and didactics. Workshop presenters from 2015 to 2019 were selected via an open call process as defined below. Didactic speakers (except for plenary speakers) were selected using the open call process for 2019 only.

We aimed to compare (1) the number and proportion of women speakers, compared with men speakers, over time and (2) the proportion of women speakers when open call processes were utilized versus that seen with closed call processes. Open call included workshops for all years and didactics for 2019; closed call included didactics for 2015 to 2018 and plenary sessions 2015 to 2019 (Table). The speaker list for the conferences was obtained from conference pamphlets or agendas available via Internet searches or obtained through attendance at the conference.

Speaker Categories and Identification Process

We determined whether each individual was a featured speaker (one whose talk was unopposed by other sessions), plenary speaker (defined as such in the conference pamphlets), whether they spoke in a group format, and whether the speaking opportunity type was a workshop or a didactic session. Numbers of featured and plenary speakers were combined because of low numbers. SHM provided deidentified conference evaluation data for each year studied. For the purposes of this study, we analyzed all speakers which included physicians, advanced practice providers, and professionals such as nurses and other interdisciplinary team members. The same speaker could be included multiple times if they had multiple speaking opportunities.

Open Call Process

We defined the “open call process” (referred to as “open call” here forward) as the process utilized by SHM that includes the following two components: (1) advertisements to members of SHM and to the medical community at large through a variety of mechanisms including emails, websites, and social media outlets and (2) an online submission process that includes names of proposed speakers and their topic and, in the case of workshops, session objectives as well as an outline of the proposed workshop. SHM committees may also submit suggestions for topics and speakers. Annual Conference Committee members then review and rate submissions on the categories of topic, organization and clarity, objectives, and speaker qualifications (with a focus on institutional, geographic, and gender diversity). Scores are assigned from 1 to 5 (with 5 being the best score) for each category and a section for comments is available. All submissions are also evaluated by the course director.

After initial committee reviews, scores with marked reviewer discrepancies are rereviewed and discussed by the committee and course director. A cutoff score is then calculated with proposals falling below the cutoff threshold omitted from further consideration. Weekly calls are then focused on subcategories (ie tracks) with emphasis on clinical and educational content. Each of the tracks have a subcommittee with track leads to curate the best content first and then focus on final speaker selection. More recently, templates are shared with the track leads that include a location to call out gender and institutional diversity. Weekly calls are held to hone the content and determine the speakers.

For the purposes of this study, when the above process was not used, the authors refer to it as “closed call.” Closed call processes do not typically involve open invitations or a peer review process. (Table)

Gender

Gender was assigned based on the speaker’s self-identification by the pronouns used in their biography submitted to the conference or on their institutional website or other websites where the speaker was referenced. Persons using she/her/hers pronouns were noted as women and persons using he/him/his were noted as men. For the purposes of this study, we conceptualized gender as binary (ie woman/man) given the limited information we had from online sources.

REDCap, a secure, Web-based application for building and managing online survey and databases, was used to collect and manage all study data.⁹

All analyses were performed using SAS Enterprise Guide 8.1 (SAS Institute, Inc., Cary, North Carolina) using retrospectively collected data. A Cochran-Armitage test for trend was used to evaluate the proportion of women speakers from 2015 to 2019. A chi-square test was used to assess the proportion of women speakers for open call processes versus that seen with closed call. One-way analysis of variance (ANOVA) was used to evaluate annual conference evaluation scores from 2015 to 2019. Either numbers with proportions or means with standard deviations have been reported. Bonferroni’s correction for multiple comparisons was applied, with a P < .008 considered statistically significant.

Between 2015 and 2019, a total of 709 workshop and didactic presentations were given by 1,261 speakers at the annual Society of Hospital Medicine Conference. Of these, 505 (40%) were women; 756 (60%) were men. There were no missing data.

From 2015 to 2019, representation of women speakers increased from 35% of all speakers to 47% of all speakers (P = .0068). Women plenary speakers increased from 23% in 2015 to 45% in 2019 (P = .0396).

The proportion of women presenters for workshops (which have utilized an open call process throughout the study period), ranged from 43% to 53% from 2015 to 2019 with no statistically significant difference in gender distribution across years (Figure).

The important findings of this study are that there has been an increase in women speakers over the last 5 years at the annual Society of Hospital Medicine Conference, that women had higher representation as speakers when open call processes were followed, and that conference scores continued to improve during the time frame studied. These findings suggest that a systematic open call process helps to support equitable speaking opportunities for men and women at a national hospital medicine conference without a negative impact on conference quality.

To recruit more diverse speakers, open call and peer review processes were used in addition to deliberate efforts at ensuring diversity in speakers. We found that over time, the proportion of women with speaking opportunities increased from 2015 to 2019. Interestingly, workshops, which had open call processes in place for the duration of the study period, had almost equal numbers of men and women presenting in all years. We also found that the number of all-men speaking groups decreased between 2015 and 2019.

A single process change can impact gender equity, but the target of true equity is expected to require additional measures such as assessment of committee structures and diversity, checklists, and reporting structures (data analysis and plans when goals not achieved).^10-13 For instance, the American Society for Microbiology General Meeting was able to achieve gender equity in speakers by a multifold approach including ensuring the program committee was aware of gender statistics, increasing female representation among session convener teams, and direct instruction to try to avoid all-male sessions.¹¹

It is important to acknowledge that these processes do require valuable resources including time. SHM has historically used committee volunteers to conduct the peer review process with each committee member reviewing 20 to 30 workshop submissions and 30 to 50 didactic sessions. While open processes with peer review seem to generate improved gender equity, ensuring processes are in place during the selection process is also key.

Several recent notable efforts to enhance gender equity and to increase diversity have been proposed. One such example of a process that may further improve gender equity was proposed by editors at the Journal of Hospital Medicine to assess current representation via demographics including gender, race, and ethnicity of authors with plans to assess patterns in the coming years.¹⁴ The American College of Physicians also published a position paper on achieving gender equity with a recommendation that organizational policies and procedures should be implemented that address implicit bias.¹⁵

Our study showed that, from 2015 to 2019, conference evaluations saw a significant increase in the score concurrently with the rise in proportion of women speakers. This finding suggests that quality does not seem to be affected by this new methodology for speaker selection and in fact this methodology may actually help improve the overall quality of the conference. To our knowledge, this is one of the first studies to concurrently evaluate speaker gender equity with conference quality.

Our study offers several strengths. This study took a pragmatic approach to understanding how processes can impact gender equity, and we were able to take advantage of the evolution of the open call system (ie workshops which have been an open call process for the duration of the study versus speaking opportunities that were not).

Our study also has several limitations. First, this study is retrospective in nature and thus other processes could have contributed to the improved gender equity, such as an organization’s priorities over time. During this study period, the SHM conference saw an average 3% increase annually in women speakers and an increase of 8% from 2018 to 2019 for all speakers compared to national trends of approximately 1%,⁶ which suggests that the open call processes in place could be contributing to the overall increases seen. Similarly, because of the retrospective nature of the study, we cannot be certain that the improvements in conference scores were directly the result of improved gender equity, although it does suggest that the improvements in gender equity did not have an adverse impact on the scores. We also did not assess how the composition of selection committee members for the meeting could have impacted the overall composition of the speakers. Our study looked at diversity only from the perspective of gender in a binary fashion, and thus additional studies are needed to assess how to improve diversity overall. It is unclear how this new open call for speakers affects race and ethnic diversity specifically. Identifying gender for the purposes of this study was facilitated by speakers providing their own biographies and the respective pronouns used in those biographies, and thus gender was easier to ascertain than race and ethnicity, which are not as readily available. For organizations to understand their diversity, equity, and inclusion efforts, enhancing the ability to fairly track and measure diversity will be key. Lastly, understanding of the exact composition of hospitalists from both a gender and race/ethnicity perspective is lacking. Studies have suggested that, based upon those surveyed or studied, there is a fairly equal balance of men and women albeit in academic groups.³

An open call approach to speakers at a national hospitalist conference seems to have contributed to improvements regarding gender equity in speaking opportunities with a concurrent improvement in overall rating of the conference. The open call system is a potential mechanism that other institutions and organizations could employ to enhance their diversity efforts.

Acknowledgments

Society of Hospital Medicine Diversity, Equity, Inclusion Special Interest Group

Work Group for SPEAK UP: Marisha Burden, MD, Daniel Cabrera, MD, Amira del Pino-Jones, MD, Areeba Kara, MD, Angela Keniston, MSPH, Keshav Khanijow, MD, Flora Kisuule, MD, Chiara Mandel, Benji Mathews, MD, David Paje, MD, Stephan Papp, MD, Snehal Patel, MD, Suchita Shah Sata, MD, Dustin Smith, MD, Kevin Vuernick

Persistent gender disparities exist in pay,^1,2 leadership opportunities,^3,4 promotion,⁵ and speaking opportunities.⁶ While the gender distribution of the hospitalist workforce may be approaching parity,^3,7,8 gender differences in leadership, speakership, and authorship have already been noted in hospital medicine.³ Between 2006 and 2012, women constituted less than a third (26%) of the presenters at the national conferences of the Society of Hospital Medicine (SHM) and the Society of General Internal Medicine (SGIM).³

The SHM Annual Meeting has historically had an “open call” peer review process for workshop presenters with the goal of increasing the diversity of presenters. In 2019, this process was expanded to include didactic speakers. Our aim in this study was to assess whether these open call procedures resulted in improved representation of women speakers and how the proportion of women speakers affects the overall evaluation scores of the conference. Our hypothesis was that the introduction of an open call process for the SHM conference didactic speakers would be associated with an increased proportion of women speakers, compared with the closed call processes, without a negative impact on conference scores.

The study is a retrospective evaluation of data collected regarding speakers at the annual SHM conference from 2015 to 2019. The SHM national conference typically has two main types of offerings: workshops and didactics. Workshop presenters from 2015 to 2019 were selected via an open call process as defined below. Didactic speakers (except for plenary speakers) were selected using the open call process for 2019 only.

We aimed to compare (1) the number and proportion of women speakers, compared with men speakers, over time and (2) the proportion of women speakers when open call processes were utilized versus that seen with closed call processes. Open call included workshops for all years and didactics for 2019; closed call included didactics for 2015 to 2018 and plenary sessions 2015 to 2019 (Table). The speaker list for the conferences was obtained from conference pamphlets or agendas available via Internet searches or obtained through attendance at the conference.

Speaker Categories and Identification Process

We determined whether each individual was a featured speaker (one whose talk was unopposed by other sessions), plenary speaker (defined as such in the conference pamphlets), whether they spoke in a group format, and whether the speaking opportunity type was a workshop or a didactic session. Numbers of featured and plenary speakers were combined because of low numbers. SHM provided deidentified conference evaluation data for each year studied. For the purposes of this study, we analyzed all speakers which included physicians, advanced practice providers, and professionals such as nurses and other interdisciplinary team members. The same speaker could be included multiple times if they had multiple speaking opportunities.

Open Call Process

We defined the “open call process” (referred to as “open call” here forward) as the process utilized by SHM that includes the following two components: (1) advertisements to members of SHM and to the medical community at large through a variety of mechanisms including emails, websites, and social media outlets and (2) an online submission process that includes names of proposed speakers and their topic and, in the case of workshops, session objectives as well as an outline of the proposed workshop. SHM committees may also submit suggestions for topics and speakers. Annual Conference Committee members then review and rate submissions on the categories of topic, organization and clarity, objectives, and speaker qualifications (with a focus on institutional, geographic, and gender diversity). Scores are assigned from 1 to 5 (with 5 being the best score) for each category and a section for comments is available. All submissions are also evaluated by the course director.

After initial committee reviews, scores with marked reviewer discrepancies are rereviewed and discussed by the committee and course director. A cutoff score is then calculated with proposals falling below the cutoff threshold omitted from further consideration. Weekly calls are then focused on subcategories (ie tracks) with emphasis on clinical and educational content. Each of the tracks have a subcommittee with track leads to curate the best content first and then focus on final speaker selection. More recently, templates are shared with the track leads that include a location to call out gender and institutional diversity. Weekly calls are held to hone the content and determine the speakers.

For the purposes of this study, when the above process was not used, the authors refer to it as “closed call.” Closed call processes do not typically involve open invitations or a peer review process. (Table)

Gender

Gender was assigned based on the speaker’s self-identification by the pronouns used in their biography submitted to the conference or on their institutional website or other websites where the speaker was referenced. Persons using she/her/hers pronouns were noted as women and persons using he/him/his were noted as men. For the purposes of this study, we conceptualized gender as binary (ie woman/man) given the limited information we had from online sources.

REDCap, a secure, Web-based application for building and managing online survey and databases, was used to collect and manage all study data.⁹

All analyses were performed using SAS Enterprise Guide 8.1 (SAS Institute, Inc., Cary, North Carolina) using retrospectively collected data. A Cochran-Armitage test for trend was used to evaluate the proportion of women speakers from 2015 to 2019. A chi-square test was used to assess the proportion of women speakers for open call processes versus that seen with closed call. One-way analysis of variance (ANOVA) was used to evaluate annual conference evaluation scores from 2015 to 2019. Either numbers with proportions or means with standard deviations have been reported. Bonferroni’s correction for multiple comparisons was applied, with a P < .008 considered statistically significant.

Between 2015 and 2019, a total of 709 workshop and didactic presentations were given by 1,261 speakers at the annual Society of Hospital Medicine Conference. Of these, 505 (40%) were women; 756 (60%) were men. There were no missing data.

From 2015 to 2019, representation of women speakers increased from 35% of all speakers to 47% of all speakers (P = .0068). Women plenary speakers increased from 23% in 2015 to 45% in 2019 (P = .0396).

The proportion of women presenters for workshops (which have utilized an open call process throughout the study period), ranged from 43% to 53% from 2015 to 2019 with no statistically significant difference in gender distribution across years (Figure).

The important findings of this study are that there has been an increase in women speakers over the last 5 years at the annual Society of Hospital Medicine Conference, that women had higher representation as speakers when open call processes were followed, and that conference scores continued to improve during the time frame studied. These findings suggest that a systematic open call process helps to support equitable speaking opportunities for men and women at a national hospital medicine conference without a negative impact on conference quality.

To recruit more diverse speakers, open call and peer review processes were used in addition to deliberate efforts at ensuring diversity in speakers. We found that over time, the proportion of women with speaking opportunities increased from 2015 to 2019. Interestingly, workshops, which had open call processes in place for the duration of the study period, had almost equal numbers of men and women presenting in all years. We also found that the number of all-men speaking groups decreased between 2015 and 2019.

A single process change can impact gender equity, but the target of true equity is expected to require additional measures such as assessment of committee structures and diversity, checklists, and reporting structures (data analysis and plans when goals not achieved).^10-13 For instance, the American Society for Microbiology General Meeting was able to achieve gender equity in speakers by a multifold approach including ensuring the program committee was aware of gender statistics, increasing female representation among session convener teams, and direct instruction to try to avoid all-male sessions.¹¹

It is important to acknowledge that these processes do require valuable resources including time. SHM has historically used committee volunteers to conduct the peer review process with each committee member reviewing 20 to 30 workshop submissions and 30 to 50 didactic sessions. While open processes with peer review seem to generate improved gender equity, ensuring processes are in place during the selection process is also key.

Several recent notable efforts to enhance gender equity and to increase diversity have been proposed. One such example of a process that may further improve gender equity was proposed by editors at the Journal of Hospital Medicine to assess current representation via demographics including gender, race, and ethnicity of authors with plans to assess patterns in the coming years.¹⁴ The American College of Physicians also published a position paper on achieving gender equity with a recommendation that organizational policies and procedures should be implemented that address implicit bias.¹⁵

Our study showed that, from 2015 to 2019, conference evaluations saw a significant increase in the score concurrently with the rise in proportion of women speakers. This finding suggests that quality does not seem to be affected by this new methodology for speaker selection and in fact this methodology may actually help improve the overall quality of the conference. To our knowledge, this is one of the first studies to concurrently evaluate speaker gender equity with conference quality.

Our study offers several strengths. This study took a pragmatic approach to understanding how processes can impact gender equity, and we were able to take advantage of the evolution of the open call system (ie workshops which have been an open call process for the duration of the study versus speaking opportunities that were not).

Our study also has several limitations. First, this study is retrospective in nature and thus other processes could have contributed to the improved gender equity, such as an organization’s priorities over time. During this study period, the SHM conference saw an average 3% increase annually in women speakers and an increase of 8% from 2018 to 2019 for all speakers compared to national trends of approximately 1%,⁶ which suggests that the open call processes in place could be contributing to the overall increases seen. Similarly, because of the retrospective nature of the study, we cannot be certain that the improvements in conference scores were directly the result of improved gender equity, although it does suggest that the improvements in gender equity did not have an adverse impact on the scores. We also did not assess how the composition of selection committee members for the meeting could have impacted the overall composition of the speakers. Our study looked at diversity only from the perspective of gender in a binary fashion, and thus additional studies are needed to assess how to improve diversity overall. It is unclear how this new open call for speakers affects race and ethnic diversity specifically. Identifying gender for the purposes of this study was facilitated by speakers providing their own biographies and the respective pronouns used in those biographies, and thus gender was easier to ascertain than race and ethnicity, which are not as readily available. For organizations to understand their diversity, equity, and inclusion efforts, enhancing the ability to fairly track and measure diversity will be key. Lastly, understanding of the exact composition of hospitalists from both a gender and race/ethnicity perspective is lacking. Studies have suggested that, based upon those surveyed or studied, there is a fairly equal balance of men and women albeit in academic groups.³

An open call approach to speakers at a national hospitalist conference seems to have contributed to improvements regarding gender equity in speaking opportunities with a concurrent improvement in overall rating of the conference. The open call system is a potential mechanism that other institutions and organizations could employ to enhance their diversity efforts.

Acknowledgments

Society of Hospital Medicine Diversity, Equity, Inclusion Special Interest Group

Work Group for SPEAK UP: Marisha Burden, MD, Daniel Cabrera, MD, Amira del Pino-Jones, MD, Areeba Kara, MD, Angela Keniston, MSPH, Keshav Khanijow, MD, Flora Kisuule, MD, Chiara Mandel, Benji Mathews, MD, David Paje, MD, Stephan Papp, MD, Snehal Patel, MD, Suchita Shah Sata, MD, Dustin Smith, MD, Kevin Vuernick

Persistent gender disparities exist in pay,^1,2 leadership opportunities,^3,4 promotion,⁵ and speaking opportunities.⁶ While the gender distribution of the hospitalist workforce may be approaching parity,^3,7,8 gender differences in leadership, speakership, and authorship have already been noted in hospital medicine.³ Between 2006 and 2012, women constituted less than a third (26%) of the presenters at the national conferences of the Society of Hospital Medicine (SHM) and the Society of General Internal Medicine (SGIM).³

The SHM Annual Meeting has historically had an “open call” peer review process for workshop presenters with the goal of increasing the diversity of presenters. In 2019, this process was expanded to include didactic speakers. Our aim in this study was to assess whether these open call procedures resulted in improved representation of women speakers and how the proportion of women speakers affects the overall evaluation scores of the conference. Our hypothesis was that the introduction of an open call process for the SHM conference didactic speakers would be associated with an increased proportion of women speakers, compared with the closed call processes, without a negative impact on conference scores.

The study is a retrospective evaluation of data collected regarding speakers at the annual SHM conference from 2015 to 2019. The SHM national conference typically has two main types of offerings: workshops and didactics. Workshop presenters from 2015 to 2019 were selected via an open call process as defined below. Didactic speakers (except for plenary speakers) were selected using the open call process for 2019 only.

We aimed to compare (1) the number and proportion of women speakers, compared with men speakers, over time and (2) the proportion of women speakers when open call processes were utilized versus that seen with closed call processes. Open call included workshops for all years and didactics for 2019; closed call included didactics for 2015 to 2018 and plenary sessions 2015 to 2019 (Table). The speaker list for the conferences was obtained from conference pamphlets or agendas available via Internet searches or obtained through attendance at the conference.

Speaker Categories and Identification Process

We determined whether each individual was a featured speaker (one whose talk was unopposed by other sessions), plenary speaker (defined as such in the conference pamphlets), whether they spoke in a group format, and whether the speaking opportunity type was a workshop or a didactic session. Numbers of featured and plenary speakers were combined because of low numbers. SHM provided deidentified conference evaluation data for each year studied. For the purposes of this study, we analyzed all speakers which included physicians, advanced practice providers, and professionals such as nurses and other interdisciplinary team members. The same speaker could be included multiple times if they had multiple speaking opportunities.

Open Call Process

We defined the “open call process” (referred to as “open call” here forward) as the process utilized by SHM that includes the following two components: (1) advertisements to members of SHM and to the medical community at large through a variety of mechanisms including emails, websites, and social media outlets and (2) an online submission process that includes names of proposed speakers and their topic and, in the case of workshops, session objectives as well as an outline of the proposed workshop. SHM committees may also submit suggestions for topics and speakers. Annual Conference Committee members then review and rate submissions on the categories of topic, organization and clarity, objectives, and speaker qualifications (with a focus on institutional, geographic, and gender diversity). Scores are assigned from 1 to 5 (with 5 being the best score) for each category and a section for comments is available. All submissions are also evaluated by the course director.

After initial committee reviews, scores with marked reviewer discrepancies are rereviewed and discussed by the committee and course director. A cutoff score is then calculated with proposals falling below the cutoff threshold omitted from further consideration. Weekly calls are then focused on subcategories (ie tracks) with emphasis on clinical and educational content. Each of the tracks have a subcommittee with track leads to curate the best content first and then focus on final speaker selection. More recently, templates are shared with the track leads that include a location to call out gender and institutional diversity. Weekly calls are held to hone the content and determine the speakers.

For the purposes of this study, when the above process was not used, the authors refer to it as “closed call.” Closed call processes do not typically involve open invitations or a peer review process. (Table)

Gender

Gender was assigned based on the speaker’s self-identification by the pronouns used in their biography submitted to the conference or on their institutional website or other websites where the speaker was referenced. Persons using she/her/hers pronouns were noted as women and persons using he/him/his were noted as men. For the purposes of this study, we conceptualized gender as binary (ie woman/man) given the limited information we had from online sources.

REDCap, a secure, Web-based application for building and managing online survey and databases, was used to collect and manage all study data.⁹

All analyses were performed using SAS Enterprise Guide 8.1 (SAS Institute, Inc., Cary, North Carolina) using retrospectively collected data. A Cochran-Armitage test for trend was used to evaluate the proportion of women speakers from 2015 to 2019. A chi-square test was used to assess the proportion of women speakers for open call processes versus that seen with closed call. One-way analysis of variance (ANOVA) was used to evaluate annual conference evaluation scores from 2015 to 2019. Either numbers with proportions or means with standard deviations have been reported. Bonferroni’s correction for multiple comparisons was applied, with a P < .008 considered statistically significant.

Between 2015 and 2019, a total of 709 workshop and didactic presentations were given by 1,261 speakers at the annual Society of Hospital Medicine Conference. Of these, 505 (40%) were women; 756 (60%) were men. There were no missing data.

From 2015 to 2019, representation of women speakers increased from 35% of all speakers to 47% of all speakers (P = .0068). Women plenary speakers increased from 23% in 2015 to 45% in 2019 (P = .0396).

The proportion of women presenters for workshops (which have utilized an open call process throughout the study period), ranged from 43% to 53% from 2015 to 2019 with no statistically significant difference in gender distribution across years (Figure).

The important findings of this study are that there has been an increase in women speakers over the last 5 years at the annual Society of Hospital Medicine Conference, that women had higher representation as speakers when open call processes were followed, and that conference scores continued to improve during the time frame studied. These findings suggest that a systematic open call process helps to support equitable speaking opportunities for men and women at a national hospital medicine conference without a negative impact on conference quality.

To recruit more diverse speakers, open call and peer review processes were used in addition to deliberate efforts at ensuring diversity in speakers. We found that over time, the proportion of women with speaking opportunities increased from 2015 to 2019. Interestingly, workshops, which had open call processes in place for the duration of the study period, had almost equal numbers of men and women presenting in all years. We also found that the number of all-men speaking groups decreased between 2015 and 2019.

A single process change can impact gender equity, but the target of true equity is expected to require additional measures such as assessment of committee structures and diversity, checklists, and reporting structures (data analysis and plans when goals not achieved).^10-13 For instance, the American Society for Microbiology General Meeting was able to achieve gender equity in speakers by a multifold approach including ensuring the program committee was aware of gender statistics, increasing female representation among session convener teams, and direct instruction to try to avoid all-male sessions.¹¹

It is important to acknowledge that these processes do require valuable resources including time. SHM has historically used committee volunteers to conduct the peer review process with each committee member reviewing 20 to 30 workshop submissions and 30 to 50 didactic sessions. While open processes with peer review seem to generate improved gender equity, ensuring processes are in place during the selection process is also key.

Several recent notable efforts to enhance gender equity and to increase diversity have been proposed. One such example of a process that may further improve gender equity was proposed by editors at the Journal of Hospital Medicine to assess current representation via demographics including gender, race, and ethnicity of authors with plans to assess patterns in the coming years.¹⁴ The American College of Physicians also published a position paper on achieving gender equity with a recommendation that organizational policies and procedures should be implemented that address implicit bias.¹⁵

Our study showed that, from 2015 to 2019, conference evaluations saw a significant increase in the score concurrently with the rise in proportion of women speakers. This finding suggests that quality does not seem to be affected by this new methodology for speaker selection and in fact this methodology may actually help improve the overall quality of the conference. To our knowledge, this is one of the first studies to concurrently evaluate speaker gender equity with conference quality.

Our study offers several strengths. This study took a pragmatic approach to understanding how processes can impact gender equity, and we were able to take advantage of the evolution of the open call system (ie workshops which have been an open call process for the duration of the study versus speaking opportunities that were not).

Our study also has several limitations. First, this study is retrospective in nature and thus other processes could have contributed to the improved gender equity, such as an organization’s priorities over time. During this study period, the SHM conference saw an average 3% increase annually in women speakers and an increase of 8% from 2018 to 2019 for all speakers compared to national trends of approximately 1%,⁶ which suggests that the open call processes in place could be contributing to the overall increases seen. Similarly, because of the retrospective nature of the study, we cannot be certain that the improvements in conference scores were directly the result of improved gender equity, although it does suggest that the improvements in gender equity did not have an adverse impact on the scores. We also did not assess how the composition of selection committee members for the meeting could have impacted the overall composition of the speakers. Our study looked at diversity only from the perspective of gender in a binary fashion, and thus additional studies are needed to assess how to improve diversity overall. It is unclear how this new open call for speakers affects race and ethnic diversity specifically. Identifying gender for the purposes of this study was facilitated by speakers providing their own biographies and the respective pronouns used in those biographies, and thus gender was easier to ascertain than race and ethnicity, which are not as readily available. For organizations to understand their diversity, equity, and inclusion efforts, enhancing the ability to fairly track and measure diversity will be key. Lastly, understanding of the exact composition of hospitalists from both a gender and race/ethnicity perspective is lacking. Studies have suggested that, based upon those surveyed or studied, there is a fairly equal balance of men and women albeit in academic groups.³

An open call approach to speakers at a national hospitalist conference seems to have contributed to improvements regarding gender equity in speaking opportunities with a concurrent improvement in overall rating of the conference. The open call system is a potential mechanism that other institutions and organizations could employ to enhance their diversity efforts.

Acknowledgments

Society of Hospital Medicine Diversity, Equity, Inclusion Special Interest Group

Work Group for SPEAK UP: Marisha Burden, MD, Daniel Cabrera, MD, Amira del Pino-Jones, MD, Areeba Kara, MD, Angela Keniston, MSPH, Keshav Khanijow, MD, Flora Kisuule, MD, Chiara Mandel, Benji Mathews, MD, David Paje, MD, Stephan Papp, MD, Snehal Patel, MD, Suchita Shah Sata, MD, Dustin Smith, MD, Kevin Vuernick

Not too many years ago, clinicians who treat patients with heart failure, especially those at high risk for decompensation, lamented what seemed a dearth of new drug therapy options.

Now, with the toolbox brimming with new guideline-supported alternatives, a novel investigational agent—one with a mechanism unlike that of any approved heart failure drug—has turned in positive results in a large randomized, placebo-controlled trial.

Importantly, it entered an especially high-risk population with heart failure and reduced ejection fraction (HFrEF); everyone in the trial had experienced a prior, usually quite recent, heart failure exacerbation.

In such patients, the addition of vericiguat (Merck/Bayer) to standard drug and device therapies was followed by a moderately but significantly reduced relative risk for the trial’s primary clinical endpoint over about 11 months.

Recipients benefited with a 10% drop in adjusted risk (P = .019) for cardiovascular (CV) death or first heart failure hospitalization compared to a placebo control group.

But researchers leading the 5050-patient Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), as well as unaffiliated experts who have studied the trial, say that in this case, risk reduction in absolute numbers is a more telling outcome.

“Remember who we’re talking about here in terms of the patients who have this degree of morbidity and mortality,” VICTORIA study chair Paul W. Armstrong, MD, University of Alberta, Edmonton, Canada, told theheart.org | Medscape Cardiology, pointing to the “incredible placebo-group event rate and relatively modest follow-up of 10.8 months.”

The control group’s primary-endpoint event rate was 37.8 per 100 patient-years, 4.2 points higher than the rate for patients who received vericiguat. “And from there you get a number needed to treat of 24 to prevent one event, which is low,” Armstrong said.

“Think about the hundreds of thousands of people with this disease and what that means at the public health level.” About one in four patients with heart failure experience such exacerbations each year, he said.

Armstrong is lead author on the 42-country trial’s publication today in the New England Journal of Medicine, timed to coincide with his online presentation for the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). The annual session was conducted virtually this year following the traditional live meeting’s cancelation due to the COVID-19 pandemic.

The VICTORIA presentation and publication flesh out the cursory top-line primary results that Merck unveiled in November 2019, which had not included the magnitude of the vericiguat relative benefit for the primary endpoint.

The trial represents “another win” for the treatment of heart failure, Clyde W. Yancy, MD, Northwestern University, Chicago, Illinois, said as an invited discussant following Armstrong’s presentation.

“Hospitalization for heart failure generates a major inflection point in the natural history of this condition, with a marked change in the risk for re-hospitalization and death. Up until now, no prior therapies have attenuated this risk, except for more intensive processes and care improvement strategies,” he said.

“Now we have a therapy that may be the first one to change that natural history after a person with heart failure has had a worsening event.”

Interestingly, the primary-endpoint reduction was driven by a significant drop in heart failure hospitalizations, even within a fairly short follow-up time.

“What was fascinating is that the requisite number of events were accrued in less than 12 months — meaning that inexplicably, this is one of the few times we’ve had a trial where the event rate realized was higher than the event rate predicted,” Yancy observed for theheart.org | Medscape Cardiology.

Although the effect size was similar to what was observed for dapagliflozin (Farxiga, AstraZeneca) in DAPA-HF and sacubitril/valsartan (Entresto, Novartis) in PARADIGM-HF, he said, VICTORIA’s population was much sicker and had an “astonishingly high” event rate even while receiving aggressive background heart failure therapy.

It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.

It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.

Such patients with advanced, late-stage disease are common as the latest therapies for heart failure prolong their survival, notes Lynne W. Stevenson, MD, Vanderbilt University, Nashville, Tennessee, also as an invited discussant after Armstrong’s presentation.

“It’s a unique population with longer disease duration, more severe disease, and narrow options,” one in which personalized approaches are needed. Yet VICTORIA-like patients “have been actively excluded from all the trials that have shown benefit,” she said.

“VICTORIA finally addresses this population of decompensated patients,” she said, and seems to show that vericiguat may help some of them.

At the University of Glasgow, United Kingdom, John J.V. McMurray, MBChB, MD, agreed that the relative risk reduction was “small but significant,” but also that the control group’s event rate was “very high, reflecting the inclusion and exclusion criteria.”

As a result, McMurray told theheart.org | Medscape Cardiology, there was “quite a large absolute risk reduction and small number needed to treat. Also on the positive side: no significant excess of the adverse effects we might have been concerned about,” for example, hypotension.

Vericiguat, if ultimately approved in heart failure, “isn’t going to be first-line or widely used, but it is an additional asset,” he said. “Anything that helps in heart failure is valuable. There are always patients who can’t tolerate treatments, and always people who need more done.”

It’s appealing that the drug works by a long but unfruitfully explored mechanism that has little to do directly with the renin-angiotensin-aldosterone system.

Vericiguat is a soluble guanylate cyclase stimulator that boosts cyclic guanosine monophosphate activity along several pathways, potentiating the salutary pulmonary artery–vasodilating effects of nitric oxide. It improved natriuretic peptide levels in the preceding phase 2 SOCRATES-REDUCED study.

“This is not a me-too drug. It’s a new avenue for heart failure patients,” Armstrong said in an interview. It’s taken once daily, “was relatively easy to titrate up to the target dose, pretty well tolerated, and very safe. And remarkably, you don’t need to measure renal function.”

However, because the drug’s mechanism resides in the same neighborhood of biochemical pathways affected by chronic nitrates and by phosphodiesterase type 5 inhibitors, such as sildenafil and tadalafil, patients taking those drugs were excluded from VICTORIA. Acute nitrates were allowed, however.

Symptomatic hypotension occurred in less than 10% and syncope in 4% or less of both groups; neither difference between the two groups was significant. Anemia developed more often in patients receiving vericiguat (7.6%) than in the control group (5.7%).

“We think that on balance, vericiguat is a useful alternative option for patients. But certainly the only thing we can say at this point is it works in the high-risk population that we studied,” Armstrong said. “Whether it works in lower-risk populations and how it compares is speculation, of course.”

The drug’s cost, whatever it might be if approved, is another factor affecting how it would be used, noted several observers.

“We don’t know what the cost-effectiveness will be. It should be reasonable because the benefit was on hospitalization. That’s a costly outcome,” Yancy said.

McMurray was also hopeful. “If the treatment is well tolerated and reasonably priced, it may still be a valuable asset for at least a subset of patients.”

VICTORIA was supported by Merck Sharp & Dohme Corp and Bayer AG. Armstrong discloses receiving research grants from Merck, Bayer AG, Sanofi-Aventis, Boehringer Ingelheim, and CSL Ltd and consulting fees from Merck, Bayer AG, AstraZeneca, and Novartis. Y ancy has previously disclosed no relevant financial relationships. Stevenson has previously disclosed receiving research grants from Novartis, consulting or serving on an advisory board for Abbott and travel expenses or meals from Novartis and St Jude Medical. McMurray has previously disclosed nonfinancial support or other support from AstraZeneca, Bayer, Cardiorentis, Amgen, Oxford University/Bayer, Theracos, AbbVie, DalCor, Pfizer, Merck, Novartis, GlaxoSmithKline, Bristol-Myers Squibb, and Vifor-Fresenius.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Presented March 28, 2020. Session 402-08.

N Engl J Med. Published online March 28, 2020. Full text; Circulation. Published online March 28, 2020. Full text.

This article first appeared on Medscape.com.

Not too many years ago, clinicians who treat patients with heart failure, especially those at high risk for decompensation, lamented what seemed a dearth of new drug therapy options.

Now, with the toolbox brimming with new guideline-supported alternatives, a novel investigational agent—one with a mechanism unlike that of any approved heart failure drug—has turned in positive results in a large randomized, placebo-controlled trial.

Importantly, it entered an especially high-risk population with heart failure and reduced ejection fraction (HFrEF); everyone in the trial had experienced a prior, usually quite recent, heart failure exacerbation.

In such patients, the addition of vericiguat (Merck/Bayer) to standard drug and device therapies was followed by a moderately but significantly reduced relative risk for the trial’s primary clinical endpoint over about 11 months.

Recipients benefited with a 10% drop in adjusted risk (P = .019) for cardiovascular (CV) death or first heart failure hospitalization compared to a placebo control group.

But researchers leading the 5050-patient Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), as well as unaffiliated experts who have studied the trial, say that in this case, risk reduction in absolute numbers is a more telling outcome.

“Remember who we’re talking about here in terms of the patients who have this degree of morbidity and mortality,” VICTORIA study chair Paul W. Armstrong, MD, University of Alberta, Edmonton, Canada, told theheart.org | Medscape Cardiology, pointing to the “incredible placebo-group event rate and relatively modest follow-up of 10.8 months.”

The control group’s primary-endpoint event rate was 37.8 per 100 patient-years, 4.2 points higher than the rate for patients who received vericiguat. “And from there you get a number needed to treat of 24 to prevent one event, which is low,” Armstrong said.

“Think about the hundreds of thousands of people with this disease and what that means at the public health level.” About one in four patients with heart failure experience such exacerbations each year, he said.

Armstrong is lead author on the 42-country trial’s publication today in the New England Journal of Medicine, timed to coincide with his online presentation for the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). The annual session was conducted virtually this year following the traditional live meeting’s cancelation due to the COVID-19 pandemic.

The VICTORIA presentation and publication flesh out the cursory top-line primary results that Merck unveiled in November 2019, which had not included the magnitude of the vericiguat relative benefit for the primary endpoint.

The trial represents “another win” for the treatment of heart failure, Clyde W. Yancy, MD, Northwestern University, Chicago, Illinois, said as an invited discussant following Armstrong’s presentation.

“Hospitalization for heart failure generates a major inflection point in the natural history of this condition, with a marked change in the risk for re-hospitalization and death. Up until now, no prior therapies have attenuated this risk, except for more intensive processes and care improvement strategies,” he said.

“Now we have a therapy that may be the first one to change that natural history after a person with heart failure has had a worsening event.”

Interestingly, the primary-endpoint reduction was driven by a significant drop in heart failure hospitalizations, even within a fairly short follow-up time.

“What was fascinating is that the requisite number of events were accrued in less than 12 months — meaning that inexplicably, this is one of the few times we’ve had a trial where the event rate realized was higher than the event rate predicted,” Yancy observed for theheart.org | Medscape Cardiology.

Although the effect size was similar to what was observed for dapagliflozin (Farxiga, AstraZeneca) in DAPA-HF and sacubitril/valsartan (Entresto, Novartis) in PARADIGM-HF, he said, VICTORIA’s population was much sicker and had an “astonishingly high” event rate even while receiving aggressive background heart failure therapy.

It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.

It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.

Such patients with advanced, late-stage disease are common as the latest therapies for heart failure prolong their survival, notes Lynne W. Stevenson, MD, Vanderbilt University, Nashville, Tennessee, also as an invited discussant after Armstrong’s presentation.

“It’s a unique population with longer disease duration, more severe disease, and narrow options,” one in which personalized approaches are needed. Yet VICTORIA-like patients “have been actively excluded from all the trials that have shown benefit,” she said.

“VICTORIA finally addresses this population of decompensated patients,” she said, and seems to show that vericiguat may help some of them.

At the University of Glasgow, United Kingdom, John J.V. McMurray, MBChB, MD, agreed that the relative risk reduction was “small but significant,” but also that the control group’s event rate was “very high, reflecting the inclusion and exclusion criteria.”

As a result, McMurray told theheart.org | Medscape Cardiology, there was “quite a large absolute risk reduction and small number needed to treat. Also on the positive side: no significant excess of the adverse effects we might have been concerned about,” for example, hypotension.

Vericiguat, if ultimately approved in heart failure, “isn’t going to be first-line or widely used, but it is an additional asset,” he said. “Anything that helps in heart failure is valuable. There are always patients who can’t tolerate treatments, and always people who need more done.”

It’s appealing that the drug works by a long but unfruitfully explored mechanism that has little to do directly with the renin-angiotensin-aldosterone system.

Vericiguat is a soluble guanylate cyclase stimulator that boosts cyclic guanosine monophosphate activity along several pathways, potentiating the salutary pulmonary artery–vasodilating effects of nitric oxide. It improved natriuretic peptide levels in the preceding phase 2 SOCRATES-REDUCED study.

“This is not a me-too drug. It’s a new avenue for heart failure patients,” Armstrong said in an interview. It’s taken once daily, “was relatively easy to titrate up to the target dose, pretty well tolerated, and very safe. And remarkably, you don’t need to measure renal function.”

However, because the drug’s mechanism resides in the same neighborhood of biochemical pathways affected by chronic nitrates and by phosphodiesterase type 5 inhibitors, such as sildenafil and tadalafil, patients taking those drugs were excluded from VICTORIA. Acute nitrates were allowed, however.

Symptomatic hypotension occurred in less than 10% and syncope in 4% or less of both groups; neither difference between the two groups was significant. Anemia developed more often in patients receiving vericiguat (7.6%) than in the control group (5.7%).

“We think that on balance, vericiguat is a useful alternative option for patients. But certainly the only thing we can say at this point is it works in the high-risk population that we studied,” Armstrong said. “Whether it works in lower-risk populations and how it compares is speculation, of course.”

The drug’s cost, whatever it might be if approved, is another factor affecting how it would be used, noted several observers.

“We don’t know what the cost-effectiveness will be. It should be reasonable because the benefit was on hospitalization. That’s a costly outcome,” Yancy said.

McMurray was also hopeful. “If the treatment is well tolerated and reasonably priced, it may still be a valuable asset for at least a subset of patients.”

VICTORIA was supported by Merck Sharp & Dohme Corp and Bayer AG. Armstrong discloses receiving research grants from Merck, Bayer AG, Sanofi-Aventis, Boehringer Ingelheim, and CSL Ltd and consulting fees from Merck, Bayer AG, AstraZeneca, and Novartis. Y ancy has previously disclosed no relevant financial relationships. Stevenson has previously disclosed receiving research grants from Novartis, consulting or serving on an advisory board for Abbott and travel expenses or meals from Novartis and St Jude Medical. McMurray has previously disclosed nonfinancial support or other support from AstraZeneca, Bayer, Cardiorentis, Amgen, Oxford University/Bayer, Theracos, AbbVie, DalCor, Pfizer, Merck, Novartis, GlaxoSmithKline, Bristol-Myers Squibb, and Vifor-Fresenius.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Presented March 28, 2020. Session 402-08.

N Engl J Med. Published online March 28, 2020. Full text; Circulation. Published online March 28, 2020. Full text.

This article first appeared on Medscape.com.

Not too many years ago, clinicians who treat patients with heart failure, especially those at high risk for decompensation, lamented what seemed a dearth of new drug therapy options.

Now, with the toolbox brimming with new guideline-supported alternatives, a novel investigational agent—one with a mechanism unlike that of any approved heart failure drug—has turned in positive results in a large randomized, placebo-controlled trial.

Importantly, it entered an especially high-risk population with heart failure and reduced ejection fraction (HFrEF); everyone in the trial had experienced a prior, usually quite recent, heart failure exacerbation.

In such patients, the addition of vericiguat (Merck/Bayer) to standard drug and device therapies was followed by a moderately but significantly reduced relative risk for the trial’s primary clinical endpoint over about 11 months.

Recipients benefited with a 10% drop in adjusted risk (P = .019) for cardiovascular (CV) death or first heart failure hospitalization compared to a placebo control group.

But researchers leading the 5050-patient Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), as well as unaffiliated experts who have studied the trial, say that in this case, risk reduction in absolute numbers is a more telling outcome.

“Remember who we’re talking about here in terms of the patients who have this degree of morbidity and mortality,” VICTORIA study chair Paul W. Armstrong, MD, University of Alberta, Edmonton, Canada, told theheart.org | Medscape Cardiology, pointing to the “incredible placebo-group event rate and relatively modest follow-up of 10.8 months.”

The control group’s primary-endpoint event rate was 37.8 per 100 patient-years, 4.2 points higher than the rate for patients who received vericiguat. “And from there you get a number needed to treat of 24 to prevent one event, which is low,” Armstrong said.

“Think about the hundreds of thousands of people with this disease and what that means at the public health level.” About one in four patients with heart failure experience such exacerbations each year, he said.

Armstrong is lead author on the 42-country trial’s publication today in the New England Journal of Medicine, timed to coincide with his online presentation for the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). The annual session was conducted virtually this year following the traditional live meeting’s cancelation due to the COVID-19 pandemic.

The VICTORIA presentation and publication flesh out the cursory top-line primary results that Merck unveiled in November 2019, which had not included the magnitude of the vericiguat relative benefit for the primary endpoint.

The trial represents “another win” for the treatment of heart failure, Clyde W. Yancy, MD, Northwestern University, Chicago, Illinois, said as an invited discussant following Armstrong’s presentation.

“Hospitalization for heart failure generates a major inflection point in the natural history of this condition, with a marked change in the risk for re-hospitalization and death. Up until now, no prior therapies have attenuated this risk, except for more intensive processes and care improvement strategies,” he said.

“Now we have a therapy that may be the first one to change that natural history after a person with heart failure has had a worsening event.”

Interestingly, the primary-endpoint reduction was driven by a significant drop in heart failure hospitalizations, even within a fairly short follow-up time.

“What was fascinating is that the requisite number of events were accrued in less than 12 months — meaning that inexplicably, this is one of the few times we’ve had a trial where the event rate realized was higher than the event rate predicted,” Yancy observed for theheart.org | Medscape Cardiology.

Although the effect size was similar to what was observed for dapagliflozin (Farxiga, AstraZeneca) in DAPA-HF and sacubitril/valsartan (Entresto, Novartis) in PARADIGM-HF, he said, VICTORIA’s population was much sicker and had an “astonishingly high” event rate even while receiving aggressive background heart failure therapy.

It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.

It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.

Such patients with advanced, late-stage disease are common as the latest therapies for heart failure prolong their survival, notes Lynne W. Stevenson, MD, Vanderbilt University, Nashville, Tennessee, also as an invited discussant after Armstrong’s presentation.

“It’s a unique population with longer disease duration, more severe disease, and narrow options,” one in which personalized approaches are needed. Yet VICTORIA-like patients “have been actively excluded from all the trials that have shown benefit,” she said.

“VICTORIA finally addresses this population of decompensated patients,” she said, and seems to show that vericiguat may help some of them.

At the University of Glasgow, United Kingdom, John J.V. McMurray, MBChB, MD, agreed that the relative risk reduction was “small but significant,” but also that the control group’s event rate was “very high, reflecting the inclusion and exclusion criteria.”

As a result, McMurray told theheart.org | Medscape Cardiology, there was “quite a large absolute risk reduction and small number needed to treat. Also on the positive side: no significant excess of the adverse effects we might have been concerned about,” for example, hypotension.

Vericiguat, if ultimately approved in heart failure, “isn’t going to be first-line or widely used, but it is an additional asset,” he said. “Anything that helps in heart failure is valuable. There are always patients who can’t tolerate treatments, and always people who need more done.”

It’s appealing that the drug works by a long but unfruitfully explored mechanism that has little to do directly with the renin-angiotensin-aldosterone system.

Vericiguat is a soluble guanylate cyclase stimulator that boosts cyclic guanosine monophosphate activity along several pathways, potentiating the salutary pulmonary artery–vasodilating effects of nitric oxide. It improved natriuretic peptide levels in the preceding phase 2 SOCRATES-REDUCED study.

“This is not a me-too drug. It’s a new avenue for heart failure patients,” Armstrong said in an interview. It’s taken once daily, “was relatively easy to titrate up to the target dose, pretty well tolerated, and very safe. And remarkably, you don’t need to measure renal function.”

However, because the drug’s mechanism resides in the same neighborhood of biochemical pathways affected by chronic nitrates and by phosphodiesterase type 5 inhibitors, such as sildenafil and tadalafil, patients taking those drugs were excluded from VICTORIA. Acute nitrates were allowed, however.

Symptomatic hypotension occurred in less than 10% and syncope in 4% or less of both groups; neither difference between the two groups was significant. Anemia developed more often in patients receiving vericiguat (7.6%) than in the control group (5.7%).

“We think that on balance, vericiguat is a useful alternative option for patients. But certainly the only thing we can say at this point is it works in the high-risk population that we studied,” Armstrong said. “Whether it works in lower-risk populations and how it compares is speculation, of course.”

The drug’s cost, whatever it might be if approved, is another factor affecting how it would be used, noted several observers.

“We don’t know what the cost-effectiveness will be. It should be reasonable because the benefit was on hospitalization. That’s a costly outcome,” Yancy said.

McMurray was also hopeful. “If the treatment is well tolerated and reasonably priced, it may still be a valuable asset for at least a subset of patients.”

VICTORIA was supported by Merck Sharp & Dohme Corp and Bayer AG. Armstrong discloses receiving research grants from Merck, Bayer AG, Sanofi-Aventis, Boehringer Ingelheim, and CSL Ltd and consulting fees from Merck, Bayer AG, AstraZeneca, and Novartis. Y ancy has previously disclosed no relevant financial relationships. Stevenson has previously disclosed receiving research grants from Novartis, consulting or serving on an advisory board for Abbott and travel expenses or meals from Novartis and St Jude Medical. McMurray has previously disclosed nonfinancial support or other support from AstraZeneca, Bayer, Cardiorentis, Amgen, Oxford University/Bayer, Theracos, AbbVie, DalCor, Pfizer, Merck, Novartis, GlaxoSmithKline, Bristol-Myers Squibb, and Vifor-Fresenius.

American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). Presented March 28, 2020. Session 402-08.

N Engl J Med. Published online March 28, 2020. Full text; Circulation. Published online March 28, 2020. Full text.

This article first appeared on Medscape.com.