SAN DIEGO – In a 10-year analysis, a landmark study of partial-breast and reduced-dose radiotherapy in early breast cancer continues to show that the treatments are noninferior to full-breast therapy despite reduced radiation exposure.

The follow-up analysis of the 2,016-subject IMPORT LOW study found that 10-year overall survival rates were 87.8% (95% confidence interval, 84.9-90.1) for a full-breast radiation group, 87.2% (95% CI, 84.3-89.6) for a reduced-dose group, and 90.3% (95% CI, 87.7-92.4) in a partial-breast group. Breast cancer radiotherapy specialist Anna Kirby, MB, MD (Res), MA, of the Royal Marsden and Institute of Cancer Research, London, reported the results at the annual meeting of the American Society for Radiation Oncology.

Ipsilateral breast tumor relapse was also similar in the three groups at the 10-year mark at 2.8% (95% CI, 1.8-4.5), 1.9% (95% CI, 1.1-3.4), and 2.8% (95% CI, 1.7-4.5), respectively. Moderate/marked adverse effects were deemed to be low.

Dr. Kirby said the new findings are not “practice-changing.” However, “this complementary data supporting the change in practice that happened in the UK and elsewhere following the publication back in 2017.”

The findings are “reassuring,” breast cancer radiology specialist Robert W. Mutter, MD, of the Mayo Clinic, Rochester, Minn., said in an interview after reviewing the study findings. While the outcomes and adverse events are similar between the groups, “partial-breast irradiation is attractive because it exposes less normal tissue such as the heart and lungs than whole-breast irradiation. This could lead to fewer side effects for patients later in life at a population level. Partial-breast irradiation should be considered a standard of care in selected patients.”

In a presentation at ASTRO, Dr. Kirby provided background about the motivation for the study. It was clear that radiotherapy reduces local recurrence by up to two-thirds in early breast cancer, she said. “But in a population with excellent prognosis, this translates into relatively small absolute benefits from radiotherapy for many of our lower-risk patients,” she said. “All patients treated are at risk of radiotherapy side effects, and these become the main hazard for many women. Radiotherapy that’s focused on the part of the breast that contained the tumor – the so-called tumor bed – may reduce the long-term complications from radiotherapy, particularly in the breast, and potentially in the heart and lung, whilst hopefully maintaining low local recurrence rates.”

The initial 5-year study was a randomized, multicenter, phase III trial of patients ≥ age 50 in the United Kingdom who were tracked since recruitment in 2007-2010 (median age, 63). All had undergone breast conservation surgery. The patients were assigned to the control group (n = 674, 40 Gy), reduced-dose (n = 673, 40 Gy) and partial-breast (n = 669, 40 Gy to partial breast only) in 15 daily treatment fractions. The initial results, published in The Lancet, reported noninferiority for both reduced-dose and partial-breast radiotherapy. Adverse effects were similar in the three groups except for change in breast appearance, which was better in partial-breast therapy vs. whole-breast, and breast harder or firmer, which was better in both partial- and reduced-dose groups vs. whole-breast.

Dr. Mutter described the IMPORT LOW trial as “a practice-changing study.”

The trial was unique since both the whole-breast and partial-breast arms received the same dosing schedule, he said, which “enables an unbiased assessment of the impact of target volume on treatment outcomes.” This contrasts “with other partial-breast irradiation studies where a different dosing schedule was employed for whole-breast and partial-breast irradiation.”

The new analysis tracked patients for a median of 121 months. “There is no difference in local recurrence rate across the three arms,” Dr. Kirby said. There were no differences in overall survival, breast cancer or cardiac deaths, she added, and “neither was there any difference in the time to any moderate or marked clinician-assessed breast normal tissue endpoint.”

Heart and lung outcomes may improve over time in the lower-dose groups because of less radiation exposure, “but we haven’t shown that yet with this data set.”

Dr. Mutter cautioned that “the results of this trial may not necessarily be extrapolated to other partial-breast irradiation techniques that treat a much smaller volume of breast tissue such as intracavitary brachytherapy and intraoperative radiotherapy. Whether these same excellent outcomes can be achieved with smaller treatment volumes is an area for further investigation.”

Funding information was not provided; the initial study was funded by Cancer Research UK. Dr. Kirby discloses travel costs paid by European Society of Radiotherapy and Oncology, and other authors have various disclosures including relationships with companies such as Pfizer, Seagen, AstraZeneca, Eli Lilly, Bayer, and Janssen. Dr. Mutter has no disclosures.
 

SAN DIEGO – In a 10-year analysis, a landmark study of partial-breast and reduced-dose radiotherapy in early breast cancer continues to show that the treatments are noninferior to full-breast therapy despite reduced radiation exposure.

The follow-up analysis of the 2,016-subject IMPORT LOW study found that 10-year overall survival rates were 87.8% (95% confidence interval, 84.9-90.1) for a full-breast radiation group, 87.2% (95% CI, 84.3-89.6) for a reduced-dose group, and 90.3% (95% CI, 87.7-92.4) in a partial-breast group. Breast cancer radiotherapy specialist Anna Kirby, MB, MD (Res), MA, of the Royal Marsden and Institute of Cancer Research, London, reported the results at the annual meeting of the American Society for Radiation Oncology.

Ipsilateral breast tumor relapse was also similar in the three groups at the 10-year mark at 2.8% (95% CI, 1.8-4.5), 1.9% (95% CI, 1.1-3.4), and 2.8% (95% CI, 1.7-4.5), respectively. Moderate/marked adverse effects were deemed to be low.

Dr. Kirby said the new findings are not “practice-changing.” However, “this complementary data supporting the change in practice that happened in the UK and elsewhere following the publication back in 2017.”

The findings are “reassuring,” breast cancer radiology specialist Robert W. Mutter, MD, of the Mayo Clinic, Rochester, Minn., said in an interview after reviewing the study findings. While the outcomes and adverse events are similar between the groups, “partial-breast irradiation is attractive because it exposes less normal tissue such as the heart and lungs than whole-breast irradiation. This could lead to fewer side effects for patients later in life at a population level. Partial-breast irradiation should be considered a standard of care in selected patients.”

In a presentation at ASTRO, Dr. Kirby provided background about the motivation for the study. It was clear that radiotherapy reduces local recurrence by up to two-thirds in early breast cancer, she said. “But in a population with excellent prognosis, this translates into relatively small absolute benefits from radiotherapy for many of our lower-risk patients,” she said. “All patients treated are at risk of radiotherapy side effects, and these become the main hazard for many women. Radiotherapy that’s focused on the part of the breast that contained the tumor – the so-called tumor bed – may reduce the long-term complications from radiotherapy, particularly in the breast, and potentially in the heart and lung, whilst hopefully maintaining low local recurrence rates.”

The initial 5-year study was a randomized, multicenter, phase III trial of patients ≥ age 50 in the United Kingdom who were tracked since recruitment in 2007-2010 (median age, 63). All had undergone breast conservation surgery. The patients were assigned to the control group (n = 674, 40 Gy), reduced-dose (n = 673, 40 Gy) and partial-breast (n = 669, 40 Gy to partial breast only) in 15 daily treatment fractions. The initial results, published in The Lancet, reported noninferiority for both reduced-dose and partial-breast radiotherapy. Adverse effects were similar in the three groups except for change in breast appearance, which was better in partial-breast therapy vs. whole-breast, and breast harder or firmer, which was better in both partial- and reduced-dose groups vs. whole-breast.

Dr. Mutter described the IMPORT LOW trial as “a practice-changing study.”

The trial was unique since both the whole-breast and partial-breast arms received the same dosing schedule, he said, which “enables an unbiased assessment of the impact of target volume on treatment outcomes.” This contrasts “with other partial-breast irradiation studies where a different dosing schedule was employed for whole-breast and partial-breast irradiation.”

The new analysis tracked patients for a median of 121 months. “There is no difference in local recurrence rate across the three arms,” Dr. Kirby said. There were no differences in overall survival, breast cancer or cardiac deaths, she added, and “neither was there any difference in the time to any moderate or marked clinician-assessed breast normal tissue endpoint.”

Heart and lung outcomes may improve over time in the lower-dose groups because of less radiation exposure, “but we haven’t shown that yet with this data set.”

Dr. Mutter cautioned that “the results of this trial may not necessarily be extrapolated to other partial-breast irradiation techniques that treat a much smaller volume of breast tissue such as intracavitary brachytherapy and intraoperative radiotherapy. Whether these same excellent outcomes can be achieved with smaller treatment volumes is an area for further investigation.”

Funding information was not provided; the initial study was funded by Cancer Research UK. Dr. Kirby discloses travel costs paid by European Society of Radiotherapy and Oncology, and other authors have various disclosures including relationships with companies such as Pfizer, Seagen, AstraZeneca, Eli Lilly, Bayer, and Janssen. Dr. Mutter has no disclosures.
 

SAN DIEGO – In a 10-year analysis, a landmark study of partial-breast and reduced-dose radiotherapy in early breast cancer continues to show that the treatments are noninferior to full-breast therapy despite reduced radiation exposure.

The follow-up analysis of the 2,016-subject IMPORT LOW study found that 10-year overall survival rates were 87.8% (95% confidence interval, 84.9-90.1) for a full-breast radiation group, 87.2% (95% CI, 84.3-89.6) for a reduced-dose group, and 90.3% (95% CI, 87.7-92.4) in a partial-breast group. Breast cancer radiotherapy specialist Anna Kirby, MB, MD (Res), MA, of the Royal Marsden and Institute of Cancer Research, London, reported the results at the annual meeting of the American Society for Radiation Oncology.

Ipsilateral breast tumor relapse was also similar in the three groups at the 10-year mark at 2.8% (95% CI, 1.8-4.5), 1.9% (95% CI, 1.1-3.4), and 2.8% (95% CI, 1.7-4.5), respectively. Moderate/marked adverse effects were deemed to be low.

Dr. Kirby said the new findings are not “practice-changing.” However, “this complementary data supporting the change in practice that happened in the UK and elsewhere following the publication back in 2017.”

The findings are “reassuring,” breast cancer radiology specialist Robert W. Mutter, MD, of the Mayo Clinic, Rochester, Minn., said in an interview after reviewing the study findings. While the outcomes and adverse events are similar between the groups, “partial-breast irradiation is attractive because it exposes less normal tissue such as the heart and lungs than whole-breast irradiation. This could lead to fewer side effects for patients later in life at a population level. Partial-breast irradiation should be considered a standard of care in selected patients.”

In a presentation at ASTRO, Dr. Kirby provided background about the motivation for the study. It was clear that radiotherapy reduces local recurrence by up to two-thirds in early breast cancer, she said. “But in a population with excellent prognosis, this translates into relatively small absolute benefits from radiotherapy for many of our lower-risk patients,” she said. “All patients treated are at risk of radiotherapy side effects, and these become the main hazard for many women. Radiotherapy that’s focused on the part of the breast that contained the tumor – the so-called tumor bed – may reduce the long-term complications from radiotherapy, particularly in the breast, and potentially in the heart and lung, whilst hopefully maintaining low local recurrence rates.”

The initial 5-year study was a randomized, multicenter, phase III trial of patients ≥ age 50 in the United Kingdom who were tracked since recruitment in 2007-2010 (median age, 63). All had undergone breast conservation surgery. The patients were assigned to the control group (n = 674, 40 Gy), reduced-dose (n = 673, 40 Gy) and partial-breast (n = 669, 40 Gy to partial breast only) in 15 daily treatment fractions. The initial results, published in The Lancet, reported noninferiority for both reduced-dose and partial-breast radiotherapy. Adverse effects were similar in the three groups except for change in breast appearance, which was better in partial-breast therapy vs. whole-breast, and breast harder or firmer, which was better in both partial- and reduced-dose groups vs. whole-breast.

Dr. Mutter described the IMPORT LOW trial as “a practice-changing study.”

The trial was unique since both the whole-breast and partial-breast arms received the same dosing schedule, he said, which “enables an unbiased assessment of the impact of target volume on treatment outcomes.” This contrasts “with other partial-breast irradiation studies where a different dosing schedule was employed for whole-breast and partial-breast irradiation.”

The new analysis tracked patients for a median of 121 months. “There is no difference in local recurrence rate across the three arms,” Dr. Kirby said. There were no differences in overall survival, breast cancer or cardiac deaths, she added, and “neither was there any difference in the time to any moderate or marked clinician-assessed breast normal tissue endpoint.”

Heart and lung outcomes may improve over time in the lower-dose groups because of less radiation exposure, “but we haven’t shown that yet with this data set.”

Dr. Mutter cautioned that “the results of this trial may not necessarily be extrapolated to other partial-breast irradiation techniques that treat a much smaller volume of breast tissue such as intracavitary brachytherapy and intraoperative radiotherapy. Whether these same excellent outcomes can be achieved with smaller treatment volumes is an area for further investigation.”

Funding information was not provided; the initial study was funded by Cancer Research UK. Dr. Kirby discloses travel costs paid by European Society of Radiotherapy and Oncology, and other authors have various disclosures including relationships with companies such as Pfizer, Seagen, AstraZeneca, Eli Lilly, Bayer, and Janssen. Dr. Mutter has no disclosures.
 

Among “bi-risk” patients with acute coronary syndrome (ACS) who received a stent and completed 9-12 months of dual-antiplatelet therapy (DAPT), those who de-escalated therapy to clopidogrel alone as opposed to continuing on clopidogrel and aspirin for 9 months had 25% less bleeding without increased ischemic risk.

The findings are from the OPT-BIRISK trial in more than 7,700 patients in China deemed “bi-risk” because they had both a high risk of clinically relevant bleeding and a high risk of major adverse cardiac and cerebral events (MACCE).

Yaling Han, MD, from General Hospital of Northern Theater Command in Shenyang, China, presented the trial in a hotline session at the annual congress of the  European Society of Cardiology.

The results provide evidence for this treatment strategy from “a large cohort seen in clinical practice in whom the question of continuing DAPT vs. deescalating to clopidogrel monotherapy at this time period has not previously been addressed,” Dr. Han said in an interview.

She acknowledged that the findings may not be generalizable to non-Asian cohorts. Also, these patients were event-free after 9 months on DAPT, so they were relatively stable. Moreover, the finding that clopidogrel monotherapy was superior to DAPT for MACCE is only hypothesis-generating.

Renato D. Lopes, MD, PhD, Duke University, Durham, N.C., the assigned discussant at the session, congratulated the authors “for an important trial in the understudied East Asian population. The OPT-BIRISK trial adds information to the complex puzzle of antithrombotic therapy after ACS,” he said.

However, he brought up a few points that should be taken into consideration when interpreting this trial, including the ones noted by Dr. Han.

In an interview, Dr. Lopes cautioned that OPT-BIRISK tested an antiplatelet strategy “in challenging patients at increased risk for bleeding and ischemic events, but I don’t think we can say this is truly a high-risk population.” Invited to reply, Dr. Han conceded that these patients constituted a relatively low-risk subset of bi-risk patients.
 

Double-edged sword

“Antiplatelet therapy is a double-edged sword: it reduces ischemic risk but increases bleeding risk. Optimal antiplatelet therapy for bi-risk ACS patients remains a clinical challenge, and unsolved problem for the cardiovascular physician,” Dr. Han said in a press briefing.

The rationale and design of OPT-BIRISK were published in the American Heart Journal in 2020.

Between February 2018 and December 2020, the researchers enrolled and randomly assigned 7,758 bi-risk patients in 101 centers in China who had completed 9-12 months of DAPT (aspirin plus either clopidogrel or ticagrelor) after drug-eluting stent implantation for ACS.

The patients were randomly assigned to receive either clopidogrel plus aspirin or clopidogrel plus placebo for 9 months, followed by 3 months of aspirin.

The primary endpoint was clinically relevant Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding, at 9 months after randomization.

Key secondary endpoints were MACCE (all-cause mortality, MI, stroke, or clinically driven revascularization), individual components of MACCE, any bleeding, and stent thrombosis at 9 months after randomization.

The patient criteria for having bi-risk ACS were:

• < 65 years old with at least one high-bleeding risk criterion and at least one high-ischemia risk criterion.
• 65-78 years old with at least one high-bleeding risk criterion or at least one high-ischemia risk criterion.
• > 75 years old.

The high bleeding risk criteria were female gender, iron deficiency anemia, stroke, taking a type 2 diabetes medication, and chronic kidney disease.

The high ischemic risk criteria included troponin-positive ACS, previous stent thrombosis, previous CV events (MI, stroke, peripheral artery disease [PAD], percutaneous coronary intervention [PCI]), on a type 2 diabetes medication, chronic kidney disease, and certain lesion characteristics.

The patients had a mean age of about 65 years and 41% were female. 

About half (52%) had type 2 diabetes, 18% had previous MI, and 15% had previous ischemic stroke. The ACS was mainly unstable angina (62%), followed by NSTEMI (17%) or STEMI (21%).

The patients had a mean high ischemic risk criteria of 3.2 and a mean high bleeding risk criteria of 1.4.

The initial DAPT treatment was aspirin and clopidogrel in three quarters of the patients and aspirin and ticagrelor in the remaining patients.

At 9 months, the primary endpoint of BARC type 2-5 bleeding occurred in 2.5% of patients in the clopidogrel plus placebo group and in 3.3% of patients in the clopidogrel plus aspirin group (hazard ratio, 0.75; 95% confidence interval, 0.57-0.97, P = .03).

“The bleeding results are not surprising,” Dr. Lopes said. Monotherapy vs. DAPT will cause less bleeding, Dr. Han agreed.

At 9 months, MACCE occurred in 2.6% of patients in the clopidogrel plus placebo group and in 3.5% of patients in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96, P = .02).

Interpreting this latter finding as “reduced risk” of MACCE “is a stretch,” Dr. Lopes cautioned.

A potential explanation for this finding in the trial is that in the comparison group (aspirin plus clopidogrel), when patients had bleeding, they might have stopped all antiplatelet therapy, and this may have led to more ischemic events, he speculated.

“The observed reduction in MACCE is plausible,” Dr. Han said. “However, according to study protocol, we assumed that clopidogrel monotherapy would be noninferior to DAPT on the risk of MACCE. The superiority of clopidogrel alone vs. DAPT on MACCE should therefore be hypothesis-generating.”

“The increased rate of MACCE in the clopidogrel plus aspirin group was surprising,” she said in a press release from the ESC, “and may be because hemorrhagic events, which are more common with ongoing DAPT, could be associated with an adrenergic state with increased platelet aggregation due to hypotension, remedial procedures to treat bleeding, and the cessation of anti-ischemic medications.”
 

A low-risk subset of bi-risk patients, commonly seen in clinical practice

At the time of the index ACS, more than 60% of the patients had unstable angina, Dr. Lopes observed, “and we know these patients are lower risk.” Also, more than 1,000 of the patients did not have at least one high-risk factor for bleeding or ischemia. Moreover, these patients had not had any clinical events in the past 9-12 months on DAPT, “so they were not truly high risk when they were randomized.

“Patients aged 75 years and above are definitely bi-risk (even without any bleeding/ischemic criteria), especially post ACS, according to much literature,” Dr. Han said.

“Although patients met the bi-risk criteria for increased ischemia and bleeding at the time of index ACS and PCI, they were free from major events for at least 6 months on DAPT, thus constituting a relatively low-risk subset of bi-risk patients,” she conceded.

“Nonetheless, these patients (mean age nearly 65 years, 41% female, 52% diabetes, 18% MI history and 15% ischemic stroke history in bi-risk study) represent a large cohort seen in clinical practice,” she said. And “according to a real-world, nationwide registry from China (the OPT-CAD study), unstable angina accounted for about 50% of all ACS patients.”

There have been more data with shorter times for stopping aspirin, so it’s difficult to reconcile those studies with data from OPT-BIRISK, according to Dr. Lopes.

For example, the 2019 TWILIGHT study in patients undergoing PCI at high risk for bleeding showed that it seems to be safe to stop aspirin after 3 months and continue ticagrelor, without an increase in ischemic events.

“The question is almost in the wrong time,” he said, noting that the field is moving in the direction of stopping aspirin earlier, according to five or six recently published trials.

It is hard to generalize from an Asian population, he agreed. “In the U.S., we have other data that suggests that for high-risk patients, you can stop aspirin earlier than 9 months. That’s what most practices are doing.”

“When you look at different drugs, different doses, different duration,” Dr. Lopes summarized, “you have thousands of different permutations,” for antiplatelet therapy strategies. “Every time we have some data in large studies it adds a piece to the puzzle.”

The study was funded by the National Key Research and Development Project in China, and by a grant from Sanofi-Aventis. Dr. Han reports no relevant financial relationships. Disclosures for the other coauthors can be found with the original article.

A version of this article first appeared on Medscape.com.

Among “bi-risk” patients with acute coronary syndrome (ACS) who received a stent and completed 9-12 months of dual-antiplatelet therapy (DAPT), those who de-escalated therapy to clopidogrel alone as opposed to continuing on clopidogrel and aspirin for 9 months had 25% less bleeding without increased ischemic risk.

The findings are from the OPT-BIRISK trial in more than 7,700 patients in China deemed “bi-risk” because they had both a high risk of clinically relevant bleeding and a high risk of major adverse cardiac and cerebral events (MACCE).

Yaling Han, MD, from General Hospital of Northern Theater Command in Shenyang, China, presented the trial in a hotline session at the annual congress of the  European Society of Cardiology.

The results provide evidence for this treatment strategy from “a large cohort seen in clinical practice in whom the question of continuing DAPT vs. deescalating to clopidogrel monotherapy at this time period has not previously been addressed,” Dr. Han said in an interview.

She acknowledged that the findings may not be generalizable to non-Asian cohorts. Also, these patients were event-free after 9 months on DAPT, so they were relatively stable. Moreover, the finding that clopidogrel monotherapy was superior to DAPT for MACCE is only hypothesis-generating.

Renato D. Lopes, MD, PhD, Duke University, Durham, N.C., the assigned discussant at the session, congratulated the authors “for an important trial in the understudied East Asian population. The OPT-BIRISK trial adds information to the complex puzzle of antithrombotic therapy after ACS,” he said.

However, he brought up a few points that should be taken into consideration when interpreting this trial, including the ones noted by Dr. Han.

In an interview, Dr. Lopes cautioned that OPT-BIRISK tested an antiplatelet strategy “in challenging patients at increased risk for bleeding and ischemic events, but I don’t think we can say this is truly a high-risk population.” Invited to reply, Dr. Han conceded that these patients constituted a relatively low-risk subset of bi-risk patients.
 

Double-edged sword

“Antiplatelet therapy is a double-edged sword: it reduces ischemic risk but increases bleeding risk. Optimal antiplatelet therapy for bi-risk ACS patients remains a clinical challenge, and unsolved problem for the cardiovascular physician,” Dr. Han said in a press briefing.

The rationale and design of OPT-BIRISK were published in the American Heart Journal in 2020.

Between February 2018 and December 2020, the researchers enrolled and randomly assigned 7,758 bi-risk patients in 101 centers in China who had completed 9-12 months of DAPT (aspirin plus either clopidogrel or ticagrelor) after drug-eluting stent implantation for ACS.

The patients were randomly assigned to receive either clopidogrel plus aspirin or clopidogrel plus placebo for 9 months, followed by 3 months of aspirin.

The primary endpoint was clinically relevant Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding, at 9 months after randomization.

Key secondary endpoints were MACCE (all-cause mortality, MI, stroke, or clinically driven revascularization), individual components of MACCE, any bleeding, and stent thrombosis at 9 months after randomization.

The patient criteria for having bi-risk ACS were:

• < 65 years old with at least one high-bleeding risk criterion and at least one high-ischemia risk criterion.
• 65-78 years old with at least one high-bleeding risk criterion or at least one high-ischemia risk criterion.
• > 75 years old.

The high bleeding risk criteria were female gender, iron deficiency anemia, stroke, taking a type 2 diabetes medication, and chronic kidney disease.

The high ischemic risk criteria included troponin-positive ACS, previous stent thrombosis, previous CV events (MI, stroke, peripheral artery disease [PAD], percutaneous coronary intervention [PCI]), on a type 2 diabetes medication, chronic kidney disease, and certain lesion characteristics.

The patients had a mean age of about 65 years and 41% were female. 

About half (52%) had type 2 diabetes, 18% had previous MI, and 15% had previous ischemic stroke. The ACS was mainly unstable angina (62%), followed by NSTEMI (17%) or STEMI (21%).

The patients had a mean high ischemic risk criteria of 3.2 and a mean high bleeding risk criteria of 1.4.

The initial DAPT treatment was aspirin and clopidogrel in three quarters of the patients and aspirin and ticagrelor in the remaining patients.

At 9 months, the primary endpoint of BARC type 2-5 bleeding occurred in 2.5% of patients in the clopidogrel plus placebo group and in 3.3% of patients in the clopidogrel plus aspirin group (hazard ratio, 0.75; 95% confidence interval, 0.57-0.97, P = .03).

“The bleeding results are not surprising,” Dr. Lopes said. Monotherapy vs. DAPT will cause less bleeding, Dr. Han agreed.

At 9 months, MACCE occurred in 2.6% of patients in the clopidogrel plus placebo group and in 3.5% of patients in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96, P = .02).

Interpreting this latter finding as “reduced risk” of MACCE “is a stretch,” Dr. Lopes cautioned.

A potential explanation for this finding in the trial is that in the comparison group (aspirin plus clopidogrel), when patients had bleeding, they might have stopped all antiplatelet therapy, and this may have led to more ischemic events, he speculated.

“The observed reduction in MACCE is plausible,” Dr. Han said. “However, according to study protocol, we assumed that clopidogrel monotherapy would be noninferior to DAPT on the risk of MACCE. The superiority of clopidogrel alone vs. DAPT on MACCE should therefore be hypothesis-generating.”

“The increased rate of MACCE in the clopidogrel plus aspirin group was surprising,” she said in a press release from the ESC, “and may be because hemorrhagic events, which are more common with ongoing DAPT, could be associated with an adrenergic state with increased platelet aggregation due to hypotension, remedial procedures to treat bleeding, and the cessation of anti-ischemic medications.”
 

A low-risk subset of bi-risk patients, commonly seen in clinical practice

At the time of the index ACS, more than 60% of the patients had unstable angina, Dr. Lopes observed, “and we know these patients are lower risk.” Also, more than 1,000 of the patients did not have at least one high-risk factor for bleeding or ischemia. Moreover, these patients had not had any clinical events in the past 9-12 months on DAPT, “so they were not truly high risk when they were randomized.

“Patients aged 75 years and above are definitely bi-risk (even without any bleeding/ischemic criteria), especially post ACS, according to much literature,” Dr. Han said.

“Although patients met the bi-risk criteria for increased ischemia and bleeding at the time of index ACS and PCI, they were free from major events for at least 6 months on DAPT, thus constituting a relatively low-risk subset of bi-risk patients,” she conceded.

“Nonetheless, these patients (mean age nearly 65 years, 41% female, 52% diabetes, 18% MI history and 15% ischemic stroke history in bi-risk study) represent a large cohort seen in clinical practice,” she said. And “according to a real-world, nationwide registry from China (the OPT-CAD study), unstable angina accounted for about 50% of all ACS patients.”

There have been more data with shorter times for stopping aspirin, so it’s difficult to reconcile those studies with data from OPT-BIRISK, according to Dr. Lopes.

For example, the 2019 TWILIGHT study in patients undergoing PCI at high risk for bleeding showed that it seems to be safe to stop aspirin after 3 months and continue ticagrelor, without an increase in ischemic events.

“The question is almost in the wrong time,” he said, noting that the field is moving in the direction of stopping aspirin earlier, according to five or six recently published trials.

It is hard to generalize from an Asian population, he agreed. “In the U.S., we have other data that suggests that for high-risk patients, you can stop aspirin earlier than 9 months. That’s what most practices are doing.”

“When you look at different drugs, different doses, different duration,” Dr. Lopes summarized, “you have thousands of different permutations,” for antiplatelet therapy strategies. “Every time we have some data in large studies it adds a piece to the puzzle.”

The study was funded by the National Key Research and Development Project in China, and by a grant from Sanofi-Aventis. Dr. Han reports no relevant financial relationships. Disclosures for the other coauthors can be found with the original article.

A version of this article first appeared on Medscape.com.

Among “bi-risk” patients with acute coronary syndrome (ACS) who received a stent and completed 9-12 months of dual-antiplatelet therapy (DAPT), those who de-escalated therapy to clopidogrel alone as opposed to continuing on clopidogrel and aspirin for 9 months had 25% less bleeding without increased ischemic risk.

The findings are from the OPT-BIRISK trial in more than 7,700 patients in China deemed “bi-risk” because they had both a high risk of clinically relevant bleeding and a high risk of major adverse cardiac and cerebral events (MACCE).

Yaling Han, MD, from General Hospital of Northern Theater Command in Shenyang, China, presented the trial in a hotline session at the annual congress of the  European Society of Cardiology.

The results provide evidence for this treatment strategy from “a large cohort seen in clinical practice in whom the question of continuing DAPT vs. deescalating to clopidogrel monotherapy at this time period has not previously been addressed,” Dr. Han said in an interview.

She acknowledged that the findings may not be generalizable to non-Asian cohorts. Also, these patients were event-free after 9 months on DAPT, so they were relatively stable. Moreover, the finding that clopidogrel monotherapy was superior to DAPT for MACCE is only hypothesis-generating.

Renato D. Lopes, MD, PhD, Duke University, Durham, N.C., the assigned discussant at the session, congratulated the authors “for an important trial in the understudied East Asian population. The OPT-BIRISK trial adds information to the complex puzzle of antithrombotic therapy after ACS,” he said.

However, he brought up a few points that should be taken into consideration when interpreting this trial, including the ones noted by Dr. Han.

In an interview, Dr. Lopes cautioned that OPT-BIRISK tested an antiplatelet strategy “in challenging patients at increased risk for bleeding and ischemic events, but I don’t think we can say this is truly a high-risk population.” Invited to reply, Dr. Han conceded that these patients constituted a relatively low-risk subset of bi-risk patients.
 

Double-edged sword

“Antiplatelet therapy is a double-edged sword: it reduces ischemic risk but increases bleeding risk. Optimal antiplatelet therapy for bi-risk ACS patients remains a clinical challenge, and unsolved problem for the cardiovascular physician,” Dr. Han said in a press briefing.

The rationale and design of OPT-BIRISK were published in the American Heart Journal in 2020.

Between February 2018 and December 2020, the researchers enrolled and randomly assigned 7,758 bi-risk patients in 101 centers in China who had completed 9-12 months of DAPT (aspirin plus either clopidogrel or ticagrelor) after drug-eluting stent implantation for ACS.

The patients were randomly assigned to receive either clopidogrel plus aspirin or clopidogrel plus placebo for 9 months, followed by 3 months of aspirin.

The primary endpoint was clinically relevant Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding, at 9 months after randomization.

Key secondary endpoints were MACCE (all-cause mortality, MI, stroke, or clinically driven revascularization), individual components of MACCE, any bleeding, and stent thrombosis at 9 months after randomization.

The patient criteria for having bi-risk ACS were:

• < 65 years old with at least one high-bleeding risk criterion and at least one high-ischemia risk criterion.
• 65-78 years old with at least one high-bleeding risk criterion or at least one high-ischemia risk criterion.
• > 75 years old.

The high bleeding risk criteria were female gender, iron deficiency anemia, stroke, taking a type 2 diabetes medication, and chronic kidney disease.

The high ischemic risk criteria included troponin-positive ACS, previous stent thrombosis, previous CV events (MI, stroke, peripheral artery disease [PAD], percutaneous coronary intervention [PCI]), on a type 2 diabetes medication, chronic kidney disease, and certain lesion characteristics.

The patients had a mean age of about 65 years and 41% were female. 

About half (52%) had type 2 diabetes, 18% had previous MI, and 15% had previous ischemic stroke. The ACS was mainly unstable angina (62%), followed by NSTEMI (17%) or STEMI (21%).

The patients had a mean high ischemic risk criteria of 3.2 and a mean high bleeding risk criteria of 1.4.

The initial DAPT treatment was aspirin and clopidogrel in three quarters of the patients and aspirin and ticagrelor in the remaining patients.

At 9 months, the primary endpoint of BARC type 2-5 bleeding occurred in 2.5% of patients in the clopidogrel plus placebo group and in 3.3% of patients in the clopidogrel plus aspirin group (hazard ratio, 0.75; 95% confidence interval, 0.57-0.97, P = .03).

“The bleeding results are not surprising,” Dr. Lopes said. Monotherapy vs. DAPT will cause less bleeding, Dr. Han agreed.

At 9 months, MACCE occurred in 2.6% of patients in the clopidogrel plus placebo group and in 3.5% of patients in the clopidogrel plus aspirin group (HR, 0.74; 95% CI, 0.57-0.96, P = .02).

Interpreting this latter finding as “reduced risk” of MACCE “is a stretch,” Dr. Lopes cautioned.

A potential explanation for this finding in the trial is that in the comparison group (aspirin plus clopidogrel), when patients had bleeding, they might have stopped all antiplatelet therapy, and this may have led to more ischemic events, he speculated.

“The observed reduction in MACCE is plausible,” Dr. Han said. “However, according to study protocol, we assumed that clopidogrel monotherapy would be noninferior to DAPT on the risk of MACCE. The superiority of clopidogrel alone vs. DAPT on MACCE should therefore be hypothesis-generating.”

“The increased rate of MACCE in the clopidogrel plus aspirin group was surprising,” she said in a press release from the ESC, “and may be because hemorrhagic events, which are more common with ongoing DAPT, could be associated with an adrenergic state with increased platelet aggregation due to hypotension, remedial procedures to treat bleeding, and the cessation of anti-ischemic medications.”
 

A low-risk subset of bi-risk patients, commonly seen in clinical practice

At the time of the index ACS, more than 60% of the patients had unstable angina, Dr. Lopes observed, “and we know these patients are lower risk.” Also, more than 1,000 of the patients did not have at least one high-risk factor for bleeding or ischemia. Moreover, these patients had not had any clinical events in the past 9-12 months on DAPT, “so they were not truly high risk when they were randomized.

“Patients aged 75 years and above are definitely bi-risk (even without any bleeding/ischemic criteria), especially post ACS, according to much literature,” Dr. Han said.

“Although patients met the bi-risk criteria for increased ischemia and bleeding at the time of index ACS and PCI, they were free from major events for at least 6 months on DAPT, thus constituting a relatively low-risk subset of bi-risk patients,” she conceded.

“Nonetheless, these patients (mean age nearly 65 years, 41% female, 52% diabetes, 18% MI history and 15% ischemic stroke history in bi-risk study) represent a large cohort seen in clinical practice,” she said. And “according to a real-world, nationwide registry from China (the OPT-CAD study), unstable angina accounted for about 50% of all ACS patients.”

There have been more data with shorter times for stopping aspirin, so it’s difficult to reconcile those studies with data from OPT-BIRISK, according to Dr. Lopes.

For example, the 2019 TWILIGHT study in patients undergoing PCI at high risk for bleeding showed that it seems to be safe to stop aspirin after 3 months and continue ticagrelor, without an increase in ischemic events.

“The question is almost in the wrong time,” he said, noting that the field is moving in the direction of stopping aspirin earlier, according to five or six recently published trials.

It is hard to generalize from an Asian population, he agreed. “In the U.S., we have other data that suggests that for high-risk patients, you can stop aspirin earlier than 9 months. That’s what most practices are doing.”

“When you look at different drugs, different doses, different duration,” Dr. Lopes summarized, “you have thousands of different permutations,” for antiplatelet therapy strategies. “Every time we have some data in large studies it adds a piece to the puzzle.”

The study was funded by the National Key Research and Development Project in China, and by a grant from Sanofi-Aventis. Dr. Han reports no relevant financial relationships. Disclosures for the other coauthors can be found with the original article.

A version of this article first appeared on Medscape.com.

A disproportionate and unique number of obstacles exist in reproductive health care for patients based on race, ethnicity, geography, socioeconomic, LGBTQ+, and disability status. These barriers represent inequality in access to reproductive medical services.

These challenges are also seen in other reproductive disorders such as polycystic ovary syndrome (PCOS), fibroids, and endometriosis. It is estimated that < 25% of individuals with infertility in the United States access the resources required to have their treatment needs met (Fertil Steril. 2015 Nov;104(5):1104-10. doi: 10.1016/j.fertnstert.2015.07.113)

Fertility CARE

In 2020, the American Society for Reproductive Medicine (ASRM) created a task force on Diversity, Equity, and Inclusion (DEI) chaired by Board Member Michael A. Thomas, MD. Two years later, the ASRM elevated this task force to a committee that is now chaired by Gloria Richard-Davis, MD. As health care systems and societies increasingly recognize these obstacles to care, I invited Dr. Thomas, the current president of the ASRM, to address this vital concern. Dr. Thomas is professor and chair, department of obstetrics and gynecology, at the University of Cincinnati.
 

While not limited to reproductive health care, how prevalent is the lack of DEI and what factors contribute to this problem?

When we established the initial ASRM DEI task force, we wanted to look at DEI issues within our profession and as an access-to-care initiative. We found that ASRM and ABOG (American Board of Obstetrics and Gynecology) were not asking questions about the makeup of our REI (Reproductive Endocrinology & Infertility) providers, nursing staff, and lab personnel. We had some older data from 2018 about the REI fellowships. Since that time, there appears to be an upward trend of people of color in REI fellowships.

University of Cincinnati

We still need more data about academic, hybrid, and private REI practices when it comes to all employees. The goal would be to increase the number of people of color in all aspects of our field.

As far as access to care, we know that people of color do not have the ability to undergo ART (assisted reproductive technology) procedures at the same rate. This could be due to affordability, slower and/or later referral patterns, and personal stigma issues. Even in mandated states, people of color are seen by IVF providers in lower numbers. There is a need for a better understanding of the access-to-care issues, especially when affordability is not a problem, and the barriers to our LGBTQ+ patients.
 

Can you provide information about actions by the ASRM DEI task force and any plans for the future?

The DEI task force is now an ASRM committee. This committee is chaired by Dr. Gloria Richard-Davis and continues to work on increasing people of color in the REI workforce and understanding and decreasing access to care issues faced by people of color and members of the LGBTQ+ community.

What can physicians do at the local, state, and national level to support DEI?

All REI and ob.gyn. physicians can work with insurance companies to work on the current barriers that stand in the way of patients who want to have a family. For example, physicians can work with insurance companies to remove their definition of infertility as exposure to sperm for 1 year before fertility coverage can take effect. Also, mandated insurance coverage in all 50 states would allow even smaller companies to require this benefit to patients.

Many people of color work in smaller companies that, unfortunately, are not required to offer IVF coverage in states where mandated insurance coverage is available. As potential encouraging news, ASRM, RESOLVE (The National Infertility Association) and other patient advocacy groups are working with each state to help enact fertility mandates.
 

Which group, if any, has been most negatively affected by a lack of DEI?

People of color, LGBTQ+ communities, people with disabilities, single individuals, and those with income challenges are the most likely to be affected by adverse DEI policies.

While it is long overdue, why do you believe DEI has become such a touchstone and pervasive movement at this time?

This is the million-dollar question. After the George Floyd death, there was a global re-examination of how people of color were treated in every aspect of society. ASRM was the first to start this DEI initiative in women’s health.

ASRM and its patient advocacy partners are working with every nonmandated state toward the goal of passing infertility legislation to dramatically reduce the financial burden on all patients. We are starting to see more states either coming on board with mandates or at least discussing the possibilities. ASRM and RESOLVE have seen some recent positive outcomes with improved insurance for military families and government workers.
 

We can all agree that access to infertility treatment, particularly IVF, is not equivalent among different racial/ethnic populations. Part of the ASRM DEI task force is to evaluate research on IVF outcomes and race/ethnicity. Can you share why pregnancy outcomes would be included to potentially improve DEI?

More research needs to be done on pregnancy outcomes in women of color. We know that women of color have a decreased pregnancy rate in ART cycles even when controlling for age and other factors. We also know that birth outcomes are worse in these women. More understanding of this problem for women of color, especially African American women needs to be done.

Estimates are that more than one in eight LGBTQ+ patients live in states where physicians can refuse to treat them. Consequently, how can we improve DEI in these regions?

As someone with a number of family members in the LGBTQ+ community, this is a problem that is close to my heart. There appear to be many barriers that are being built to disenfranchise our LGBTQ+ community members. It is up to ASRM and patient advocacy groups to work with legislators to pass more inclusive laws and for insurance companies to update their definitions of infertility to be more inclusive for all.

Any final comments?

Everyone should have the right to become a parent whether they want to now or in the future!

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

A disproportionate and unique number of obstacles exist in reproductive health care for patients based on race, ethnicity, geography, socioeconomic, LGBTQ+, and disability status. These barriers represent inequality in access to reproductive medical services.

These challenges are also seen in other reproductive disorders such as polycystic ovary syndrome (PCOS), fibroids, and endometriosis. It is estimated that < 25% of individuals with infertility in the United States access the resources required to have their treatment needs met (Fertil Steril. 2015 Nov;104(5):1104-10. doi: 10.1016/j.fertnstert.2015.07.113)

Fertility CARE

In 2020, the American Society for Reproductive Medicine (ASRM) created a task force on Diversity, Equity, and Inclusion (DEI) chaired by Board Member Michael A. Thomas, MD. Two years later, the ASRM elevated this task force to a committee that is now chaired by Gloria Richard-Davis, MD. As health care systems and societies increasingly recognize these obstacles to care, I invited Dr. Thomas, the current president of the ASRM, to address this vital concern. Dr. Thomas is professor and chair, department of obstetrics and gynecology, at the University of Cincinnati.
 

While not limited to reproductive health care, how prevalent is the lack of DEI and what factors contribute to this problem?

When we established the initial ASRM DEI task force, we wanted to look at DEI issues within our profession and as an access-to-care initiative. We found that ASRM and ABOG (American Board of Obstetrics and Gynecology) were not asking questions about the makeup of our REI (Reproductive Endocrinology & Infertility) providers, nursing staff, and lab personnel. We had some older data from 2018 about the REI fellowships. Since that time, there appears to be an upward trend of people of color in REI fellowships.

University of Cincinnati

We still need more data about academic, hybrid, and private REI practices when it comes to all employees. The goal would be to increase the number of people of color in all aspects of our field.

As far as access to care, we know that people of color do not have the ability to undergo ART (assisted reproductive technology) procedures at the same rate. This could be due to affordability, slower and/or later referral patterns, and personal stigma issues. Even in mandated states, people of color are seen by IVF providers in lower numbers. There is a need for a better understanding of the access-to-care issues, especially when affordability is not a problem, and the barriers to our LGBTQ+ patients.
 

Can you provide information about actions by the ASRM DEI task force and any plans for the future?

The DEI task force is now an ASRM committee. This committee is chaired by Dr. Gloria Richard-Davis and continues to work on increasing people of color in the REI workforce and understanding and decreasing access to care issues faced by people of color and members of the LGBTQ+ community.

What can physicians do at the local, state, and national level to support DEI?

All REI and ob.gyn. physicians can work with insurance companies to work on the current barriers that stand in the way of patients who want to have a family. For example, physicians can work with insurance companies to remove their definition of infertility as exposure to sperm for 1 year before fertility coverage can take effect. Also, mandated insurance coverage in all 50 states would allow even smaller companies to require this benefit to patients.

Many people of color work in smaller companies that, unfortunately, are not required to offer IVF coverage in states where mandated insurance coverage is available. As potential encouraging news, ASRM, RESOLVE (The National Infertility Association) and other patient advocacy groups are working with each state to help enact fertility mandates.
 

Which group, if any, has been most negatively affected by a lack of DEI?

People of color, LGBTQ+ communities, people with disabilities, single individuals, and those with income challenges are the most likely to be affected by adverse DEI policies.

While it is long overdue, why do you believe DEI has become such a touchstone and pervasive movement at this time?

This is the million-dollar question. After the George Floyd death, there was a global re-examination of how people of color were treated in every aspect of society. ASRM was the first to start this DEI initiative in women’s health.

ASRM and its patient advocacy partners are working with every nonmandated state toward the goal of passing infertility legislation to dramatically reduce the financial burden on all patients. We are starting to see more states either coming on board with mandates or at least discussing the possibilities. ASRM and RESOLVE have seen some recent positive outcomes with improved insurance for military families and government workers.
 

We can all agree that access to infertility treatment, particularly IVF, is not equivalent among different racial/ethnic populations. Part of the ASRM DEI task force is to evaluate research on IVF outcomes and race/ethnicity. Can you share why pregnancy outcomes would be included to potentially improve DEI?

More research needs to be done on pregnancy outcomes in women of color. We know that women of color have a decreased pregnancy rate in ART cycles even when controlling for age and other factors. We also know that birth outcomes are worse in these women. More understanding of this problem for women of color, especially African American women needs to be done.

Estimates are that more than one in eight LGBTQ+ patients live in states where physicians can refuse to treat them. Consequently, how can we improve DEI in these regions?

As someone with a number of family members in the LGBTQ+ community, this is a problem that is close to my heart. There appear to be many barriers that are being built to disenfranchise our LGBTQ+ community members. It is up to ASRM and patient advocacy groups to work with legislators to pass more inclusive laws and for insurance companies to update their definitions of infertility to be more inclusive for all.

Any final comments?

Everyone should have the right to become a parent whether they want to now or in the future!

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

A disproportionate and unique number of obstacles exist in reproductive health care for patients based on race, ethnicity, geography, socioeconomic, LGBTQ+, and disability status. These barriers represent inequality in access to reproductive medical services.

These challenges are also seen in other reproductive disorders such as polycystic ovary syndrome (PCOS), fibroids, and endometriosis. It is estimated that < 25% of individuals with infertility in the United States access the resources required to have their treatment needs met (Fertil Steril. 2015 Nov;104(5):1104-10. doi: 10.1016/j.fertnstert.2015.07.113)

Fertility CARE

In 2020, the American Society for Reproductive Medicine (ASRM) created a task force on Diversity, Equity, and Inclusion (DEI) chaired by Board Member Michael A. Thomas, MD. Two years later, the ASRM elevated this task force to a committee that is now chaired by Gloria Richard-Davis, MD. As health care systems and societies increasingly recognize these obstacles to care, I invited Dr. Thomas, the current president of the ASRM, to address this vital concern. Dr. Thomas is professor and chair, department of obstetrics and gynecology, at the University of Cincinnati.
 

While not limited to reproductive health care, how prevalent is the lack of DEI and what factors contribute to this problem?

When we established the initial ASRM DEI task force, we wanted to look at DEI issues within our profession and as an access-to-care initiative. We found that ASRM and ABOG (American Board of Obstetrics and Gynecology) were not asking questions about the makeup of our REI (Reproductive Endocrinology & Infertility) providers, nursing staff, and lab personnel. We had some older data from 2018 about the REI fellowships. Since that time, there appears to be an upward trend of people of color in REI fellowships.

University of Cincinnati

We still need more data about academic, hybrid, and private REI practices when it comes to all employees. The goal would be to increase the number of people of color in all aspects of our field.

As far as access to care, we know that people of color do not have the ability to undergo ART (assisted reproductive technology) procedures at the same rate. This could be due to affordability, slower and/or later referral patterns, and personal stigma issues. Even in mandated states, people of color are seen by IVF providers in lower numbers. There is a need for a better understanding of the access-to-care issues, especially when affordability is not a problem, and the barriers to our LGBTQ+ patients.
 

Can you provide information about actions by the ASRM DEI task force and any plans for the future?

The DEI task force is now an ASRM committee. This committee is chaired by Dr. Gloria Richard-Davis and continues to work on increasing people of color in the REI workforce and understanding and decreasing access to care issues faced by people of color and members of the LGBTQ+ community.

What can physicians do at the local, state, and national level to support DEI?

All REI and ob.gyn. physicians can work with insurance companies to work on the current barriers that stand in the way of patients who want to have a family. For example, physicians can work with insurance companies to remove their definition of infertility as exposure to sperm for 1 year before fertility coverage can take effect. Also, mandated insurance coverage in all 50 states would allow even smaller companies to require this benefit to patients.

Many people of color work in smaller companies that, unfortunately, are not required to offer IVF coverage in states where mandated insurance coverage is available. As potential encouraging news, ASRM, RESOLVE (The National Infertility Association) and other patient advocacy groups are working with each state to help enact fertility mandates.
 

Which group, if any, has been most negatively affected by a lack of DEI?

People of color, LGBTQ+ communities, people with disabilities, single individuals, and those with income challenges are the most likely to be affected by adverse DEI policies.

While it is long overdue, why do you believe DEI has become such a touchstone and pervasive movement at this time?

This is the million-dollar question. After the George Floyd death, there was a global re-examination of how people of color were treated in every aspect of society. ASRM was the first to start this DEI initiative in women’s health.

ASRM and its patient advocacy partners are working with every nonmandated state toward the goal of passing infertility legislation to dramatically reduce the financial burden on all patients. We are starting to see more states either coming on board with mandates or at least discussing the possibilities. ASRM and RESOLVE have seen some recent positive outcomes with improved insurance for military families and government workers.
 

We can all agree that access to infertility treatment, particularly IVF, is not equivalent among different racial/ethnic populations. Part of the ASRM DEI task force is to evaluate research on IVF outcomes and race/ethnicity. Can you share why pregnancy outcomes would be included to potentially improve DEI?

More research needs to be done on pregnancy outcomes in women of color. We know that women of color have a decreased pregnancy rate in ART cycles even when controlling for age and other factors. We also know that birth outcomes are worse in these women. More understanding of this problem for women of color, especially African American women needs to be done.

Estimates are that more than one in eight LGBTQ+ patients live in states where physicians can refuse to treat them. Consequently, how can we improve DEI in these regions?

As someone with a number of family members in the LGBTQ+ community, this is a problem that is close to my heart. There appear to be many barriers that are being built to disenfranchise our LGBTQ+ community members. It is up to ASRM and patient advocacy groups to work with legislators to pass more inclusive laws and for insurance companies to update their definitions of infertility to be more inclusive for all.

Any final comments?

Everyone should have the right to become a parent whether they want to now or in the future!

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

TOPLINE:

Matched cohort studies revealed infrequent adverse events (AEs) with either treatment, but the number needed to harm for any AE was more than three times higher with colchicine versus NSAIDs.

METHODOLOGY:

• The researchers conducted two matched retrospective cohort studies using the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics primary care datasets to compare AEs in adults initiating allopurinol for gout with and without colchicine or NSAID prophylaxis.
• For the study, 13,945 patients with gout who received colchicine were matched to 13,945 patients who received no prophylaxis. In addition, 25,980 patients with gout who received NSAIDs were matched to 25,980 who received no prophylaxis.
• The researchers used proportional hazard models to explore the associations between prophylaxis with either colchicine or NSAIDs and AEs.

TAKEAWAY:

• The incidence of most AEs was less than 200 per 10,000 patient-years, but the most common AE among patients given colchicine was diarrhea, with an incidence of 784.4 per 10,000 person-years, whereas the most common AE in those given NSAIDs was angina, with an incidence of 466.6 per 10,000 person-years.
• The number needed to harm in relation to any AE was 14.7 for colchicine, driven mainly by diarrhea, and 48.1 for NSAID.
• Compared with patients who started allopurinol without prophylaxis, those treated with colchicine were more likely to experience diarrhea, myocardial infarction, neuropathy, myalgia, and bone marrow suppression, whereas those treated with NSAIDs were more likely to experience angina, acute kidney injury, myocardial infarction, and peptic ulcer disease.
• Diarrhea, the most common AE, occurred in 17.9% of individuals who received colchicine.

IN PRACTICE:

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions and the choice between colchicine or NSAID for prophylaxis when initiating allopurinol, directly benefiting people with gout and their clinicians,” the authors write.

SOURCE:

First author Edward Roddy, MD, of Keele (England) University, and colleagues published their report online in BMJ’s Annals of the Rheumatic Diseases.

LIMITATIONS:

The study identified gout based on clinical diagnosis in primary care and only considered AEs serious enough to merit consultation or hospitalization; other limitations included the observational design and lack of data on the use of over-the-counter NSAIDs.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research’s Research for Patient Benefit program. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

Matched cohort studies revealed infrequent adverse events (AEs) with either treatment, but the number needed to harm for any AE was more than three times higher with colchicine versus NSAIDs.

METHODOLOGY:

• The researchers conducted two matched retrospective cohort studies using the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics primary care datasets to compare AEs in adults initiating allopurinol for gout with and without colchicine or NSAID prophylaxis.
• For the study, 13,945 patients with gout who received colchicine were matched to 13,945 patients who received no prophylaxis. In addition, 25,980 patients with gout who received NSAIDs were matched to 25,980 who received no prophylaxis.
• The researchers used proportional hazard models to explore the associations between prophylaxis with either colchicine or NSAIDs and AEs.

TAKEAWAY:

• The incidence of most AEs was less than 200 per 10,000 patient-years, but the most common AE among patients given colchicine was diarrhea, with an incidence of 784.4 per 10,000 person-years, whereas the most common AE in those given NSAIDs was angina, with an incidence of 466.6 per 10,000 person-years.
• The number needed to harm in relation to any AE was 14.7 for colchicine, driven mainly by diarrhea, and 48.1 for NSAID.
• Compared with patients who started allopurinol without prophylaxis, those treated with colchicine were more likely to experience diarrhea, myocardial infarction, neuropathy, myalgia, and bone marrow suppression, whereas those treated with NSAIDs were more likely to experience angina, acute kidney injury, myocardial infarction, and peptic ulcer disease.
• Diarrhea, the most common AE, occurred in 17.9% of individuals who received colchicine.

IN PRACTICE:

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions and the choice between colchicine or NSAID for prophylaxis when initiating allopurinol, directly benefiting people with gout and their clinicians,” the authors write.

SOURCE:

First author Edward Roddy, MD, of Keele (England) University, and colleagues published their report online in BMJ’s Annals of the Rheumatic Diseases.

LIMITATIONS:

The study identified gout based on clinical diagnosis in primary care and only considered AEs serious enough to merit consultation or hospitalization; other limitations included the observational design and lack of data on the use of over-the-counter NSAIDs.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research’s Research for Patient Benefit program. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

TOPLINE:

Matched cohort studies revealed infrequent adverse events (AEs) with either treatment, but the number needed to harm for any AE was more than three times higher with colchicine versus NSAIDs.

METHODOLOGY:

• The researchers conducted two matched retrospective cohort studies using the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics primary care datasets to compare AEs in adults initiating allopurinol for gout with and without colchicine or NSAID prophylaxis.
• For the study, 13,945 patients with gout who received colchicine were matched to 13,945 patients who received no prophylaxis. In addition, 25,980 patients with gout who received NSAIDs were matched to 25,980 who received no prophylaxis.
• The researchers used proportional hazard models to explore the associations between prophylaxis with either colchicine or NSAIDs and AEs.

TAKEAWAY:

• The incidence of most AEs was less than 200 per 10,000 patient-years, but the most common AE among patients given colchicine was diarrhea, with an incidence of 784.4 per 10,000 person-years, whereas the most common AE in those given NSAIDs was angina, with an incidence of 466.6 per 10,000 person-years.
• The number needed to harm in relation to any AE was 14.7 for colchicine, driven mainly by diarrhea, and 48.1 for NSAID.
• Compared with patients who started allopurinol without prophylaxis, those treated with colchicine were more likely to experience diarrhea, myocardial infarction, neuropathy, myalgia, and bone marrow suppression, whereas those treated with NSAIDs were more likely to experience angina, acute kidney injury, myocardial infarction, and peptic ulcer disease.
• Diarrhea, the most common AE, occurred in 17.9% of individuals who received colchicine.

IN PRACTICE:

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions and the choice between colchicine or NSAID for prophylaxis when initiating allopurinol, directly benefiting people with gout and their clinicians,” the authors write.

SOURCE:

First author Edward Roddy, MD, of Keele (England) University, and colleagues published their report online in BMJ’s Annals of the Rheumatic Diseases.

LIMITATIONS:

The study identified gout based on clinical diagnosis in primary care and only considered AEs serious enough to merit consultation or hospitalization; other limitations included the observational design and lack of data on the use of over-the-counter NSAIDs.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research’s Research for Patient Benefit program. The researchers had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

Opposition to the current American Board of Internal Medicine’s (ABIM’s) Maintenance of Certification (MOC) process continues to gain momentum, with the latest condemnation coming from the American Society of Hematology (ASH).

ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.

“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.

Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”

The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.

The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”

The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.

The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.

In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.

On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.

The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”

After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”

A version of this article first appeared on Medscape.com.

Opposition to the current American Board of Internal Medicine’s (ABIM’s) Maintenance of Certification (MOC) process continues to gain momentum, with the latest condemnation coming from the American Society of Hematology (ASH).

ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.

“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.

Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”

The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.

The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”

The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.

The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.

In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.

On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.

The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”

After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”

A version of this article first appeared on Medscape.com.

Opposition to the current American Board of Internal Medicine’s (ABIM’s) Maintenance of Certification (MOC) process continues to gain momentum, with the latest condemnation coming from the American Society of Hematology (ASH).

ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.

“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.

Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”

The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.

The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”

The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.

The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.

In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.

On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.

The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”

After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”

A version of this article first appeared on Medscape.com.

TOPLINE:

Research from South Korea provides additional evidence for the connection between COVID-19 and an increased risk for autoimmune conditions post infection.

METHODOLOGY:

• In this retrospective study, researchers identified 354,527 individuals diagnosed with COVID-19 via polymerase chain reaction (PCR) testing from Oct. 8, 2020, to Dec. 31, 2021.
• Researchers compared the COVID-19 group with 6,134,940 healthy individuals who had no evidence of COVID-19 to quantify the risk for autoimmune and autoinflammatory connective tissue disorders.
• Patients were followed until diagnosis, death, or end of study period (Dec. 31, 2021).

TAKEAWAY:

• Risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody–associated vasculitis, Crohn’s disease, and sarcoidosis were higher in the COVID-19 group.
• Patients with more severe COVID-19 (admitted to the ICU) were at greater risk for many autoimmune conditions, including alopecia totalis, psoriasis, vitiligo, and vasculitis.
•  

IN PRACTICE:

“Our results emphasize the need to focus on managing not only the acute stages of COVID-19 itself but also autoimmune diseases as complications of COVID-19,” the authors wrote.

SOURCE:

Sung Ha Lim, MD, of Yonsei University, Wonju, South Korea, was the first author of the study, published in JAMA Network Open.

LIMITATIONS:

The study was retrospective and was composed almost exclusively of individuals from a single ethnicity. The study could have included individuals with COVID-19 in the control group who did not undergo PCR testing. The analysis did not include detailed information on each patient, including genetic information, that could have contributed to autoimmune disease risk.

DISCLOSURES:

The study was supported by a fund from the research program of the Korea Medical Institute and by grants from the Korea Health Industry Development Institute, the Korean Ministry of Health & Welfare, and the National Research Foundation of Korea. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Research from South Korea provides additional evidence for the connection between COVID-19 and an increased risk for autoimmune conditions post infection.

METHODOLOGY:

• In this retrospective study, researchers identified 354,527 individuals diagnosed with COVID-19 via polymerase chain reaction (PCR) testing from Oct. 8, 2020, to Dec. 31, 2021.
• Researchers compared the COVID-19 group with 6,134,940 healthy individuals who had no evidence of COVID-19 to quantify the risk for autoimmune and autoinflammatory connective tissue disorders.
• Patients were followed until diagnosis, death, or end of study period (Dec. 31, 2021).

TAKEAWAY:

• Risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody–associated vasculitis, Crohn’s disease, and sarcoidosis were higher in the COVID-19 group.
• Patients with more severe COVID-19 (admitted to the ICU) were at greater risk for many autoimmune conditions, including alopecia totalis, psoriasis, vitiligo, and vasculitis.
•  

IN PRACTICE:

“Our results emphasize the need to focus on managing not only the acute stages of COVID-19 itself but also autoimmune diseases as complications of COVID-19,” the authors wrote.

SOURCE:

Sung Ha Lim, MD, of Yonsei University, Wonju, South Korea, was the first author of the study, published in JAMA Network Open.

LIMITATIONS:

The study was retrospective and was composed almost exclusively of individuals from a single ethnicity. The study could have included individuals with COVID-19 in the control group who did not undergo PCR testing. The analysis did not include detailed information on each patient, including genetic information, that could have contributed to autoimmune disease risk.

DISCLOSURES:

The study was supported by a fund from the research program of the Korea Medical Institute and by grants from the Korea Health Industry Development Institute, the Korean Ministry of Health & Welfare, and the National Research Foundation of Korea. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Research from South Korea provides additional evidence for the connection between COVID-19 and an increased risk for autoimmune conditions post infection.

METHODOLOGY:

• In this retrospective study, researchers identified 354,527 individuals diagnosed with COVID-19 via polymerase chain reaction (PCR) testing from Oct. 8, 2020, to Dec. 31, 2021.
• Researchers compared the COVID-19 group with 6,134,940 healthy individuals who had no evidence of COVID-19 to quantify the risk for autoimmune and autoinflammatory connective tissue disorders.
• Patients were followed until diagnosis, death, or end of study period (Dec. 31, 2021).

TAKEAWAY:

• Risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody–associated vasculitis, Crohn’s disease, and sarcoidosis were higher in the COVID-19 group.
• Patients with more severe COVID-19 (admitted to the ICU) were at greater risk for many autoimmune conditions, including alopecia totalis, psoriasis, vitiligo, and vasculitis.
•  

IN PRACTICE:

“Our results emphasize the need to focus on managing not only the acute stages of COVID-19 itself but also autoimmune diseases as complications of COVID-19,” the authors wrote.

SOURCE:

Sung Ha Lim, MD, of Yonsei University, Wonju, South Korea, was the first author of the study, published in JAMA Network Open.

LIMITATIONS:

The study was retrospective and was composed almost exclusively of individuals from a single ethnicity. The study could have included individuals with COVID-19 in the control group who did not undergo PCR testing. The analysis did not include detailed information on each patient, including genetic information, that could have contributed to autoimmune disease risk.

DISCLOSURES:

The study was supported by a fund from the research program of the Korea Medical Institute and by grants from the Korea Health Industry Development Institute, the Korean Ministry of Health & Welfare, and the National Research Foundation of Korea. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CARLSBAD, CALIF. – With 11 different biologics approved for the treatment of plaque psoriasis on the market, settling on which one to prescribe can be tricky.

“When you look at the list of options it can be confusing to many clinicians in deciding which one to choose,” April W. Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

Dr. Armstrong

One approach is to consider how the biologics compare in short- and long-term efficacy. “Several different meta-analyses of biologics have been conducted,” which include some head-to head studies, Dr. Armstrong said. “In terms of efficacy, [biologics] are similar at the population level,” she said.

In a meta-analysis of 71 randomized, controlled trials through July 2020, Dr. Armstrong and colleagues found that in the short-term, Psoriasis Area and Severity Index (PASI) 90 response rates at 10-16 weeks from baseline were highest for ixekizumab (72.9%), risankizumab (72.5%), and brodalumab (72%). These PASI 90 responses were significantly higher than among patients on guselkumab (65%), secukinumab (65%), infliximab (56.8%), certolizumab (400 mg: 49.6%; 200 mg: 42.2%), ustekinumab (90 mg: 47.9%; weight-based: 45.7%; 45 mg: 44.6%), adalimumab (43%), tildrakizumab (200 mg: 39.7%; 100 mg: 37.2%), etanercept (18.0%), apremilast (12.4%), and dimethyl fumarate (12.2%).

In a more recent meta-analysis, Dr. Armstrong and coauthors used area under the curve (AUC) analyses to compare the cumulative clinical benefits of biologics over 1 year. They found that the placebo-adjusted normalized maximum AUC for a PASI 100 response was greatest for ixekizumab (0.436), risankizumab (0.423), and brodalumab (0.378), followed by guselkumab (0.358), secukinumab (0.324), ustekinumab (0.201), adalimumab (0.183), and etanercept (0.087).

In Dr. Armstrong’s opinion, the tumor necrosis factor (TNF) inhibitors etanercept, infliximab, adalimumab, and certolizumab “have served their purpose for plaque psoriasis over time, but these days I would probably choose either an IL [interleukin]-17 inhibitor or an IL-23 inhibitor first,” she said. Still, TNF inhibitors “are certainly good for psoriatic arthritis, and certolizumab is appropriate for patients who are pregnant or breastfeeding,” she said. “Avoid them in patients with demyelinating disease and in those with hepatitis B. They are not preferred in patients with latent TB or advanced CHF.”

Dr. Armstrong said that there are robust efficacy data for the IL-17 inhibitors ixekizumab, secukinumab, and brodalumab in psoriasis and in the peripheral and axial forms of psoriatic arthritis (PsA). “Avoid using them in patients with a personal history of inflammatory bowel disease,” she advised.

Low rates of oral candidiasis have been reported in the literature, “but this has not been issue with our approved IL-17 inhibitors so far,” she said.

The IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and ustekinumab have robust data for psoriasis efficacy, she said, and three – guselkumab, risankizumab, and ustekinumab – are also approved for PsA. “These agents have the advantage of fewer injections, and the evidence [of efficacy] for IL-23 inhibitors continues to evolve, such as in patients with psoriatic arthritis involving the spine,” Dr. Armstrong said.

She also shared how she deals with patients who fail to respond to biologics. “Do you switch drugs, or do you dose escalate?” she asked. “In most cases, the strategy for dose escalation is to shorten the interval between the injections so the dosing is delivered more frequently.” In a case of primary failure, which Dr. Armstrong defined as a patient who has never responded optimally to a biologic, consider revisiting the diagnosis. “Maybe it’s cutaneous T-cell lymphoma or some other condition, because our current IL-17 and IL-23 medications work extremely well,” she said. “So, if you have a patient who is not responding at all, I would question the diagnosis and consider a biopsy.”

She generally waits about 6 months before switching a patient to another biologic, “to see if they’re one of the late bloomers who may catch up in efficacy,” she explained. “Switching the class of biologic is another consideration.”

If a patient had responded to the biologic for a long time and then lost response – known as secondary failure – Dr. Armstrong considers dose escalation or a switch to another agent within the same class “if it helps to address comorbidities such as PsA,” she said. “You can also try across-class switching.”

Dr. Armstrong disclosed ties with AbbVie, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Dermavant, EPI, Galderma, InCyte, Janssen, Leo, Lilly, Meiji, Modmed, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Suna, UCB, and Ventyx.

CARLSBAD, CALIF. – With 11 different biologics approved for the treatment of plaque psoriasis on the market, settling on which one to prescribe can be tricky.

“When you look at the list of options it can be confusing to many clinicians in deciding which one to choose,” April W. Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

Dr. Armstrong

One approach is to consider how the biologics compare in short- and long-term efficacy. “Several different meta-analyses of biologics have been conducted,” which include some head-to head studies, Dr. Armstrong said. “In terms of efficacy, [biologics] are similar at the population level,” she said.

In a meta-analysis of 71 randomized, controlled trials through July 2020, Dr. Armstrong and colleagues found that in the short-term, Psoriasis Area and Severity Index (PASI) 90 response rates at 10-16 weeks from baseline were highest for ixekizumab (72.9%), risankizumab (72.5%), and brodalumab (72%). These PASI 90 responses were significantly higher than among patients on guselkumab (65%), secukinumab (65%), infliximab (56.8%), certolizumab (400 mg: 49.6%; 200 mg: 42.2%), ustekinumab (90 mg: 47.9%; weight-based: 45.7%; 45 mg: 44.6%), adalimumab (43%), tildrakizumab (200 mg: 39.7%; 100 mg: 37.2%), etanercept (18.0%), apremilast (12.4%), and dimethyl fumarate (12.2%).

In a more recent meta-analysis, Dr. Armstrong and coauthors used area under the curve (AUC) analyses to compare the cumulative clinical benefits of biologics over 1 year. They found that the placebo-adjusted normalized maximum AUC for a PASI 100 response was greatest for ixekizumab (0.436), risankizumab (0.423), and brodalumab (0.378), followed by guselkumab (0.358), secukinumab (0.324), ustekinumab (0.201), adalimumab (0.183), and etanercept (0.087).

In Dr. Armstrong’s opinion, the tumor necrosis factor (TNF) inhibitors etanercept, infliximab, adalimumab, and certolizumab “have served their purpose for plaque psoriasis over time, but these days I would probably choose either an IL [interleukin]-17 inhibitor or an IL-23 inhibitor first,” she said. Still, TNF inhibitors “are certainly good for psoriatic arthritis, and certolizumab is appropriate for patients who are pregnant or breastfeeding,” she said. “Avoid them in patients with demyelinating disease and in those with hepatitis B. They are not preferred in patients with latent TB or advanced CHF.”

Dr. Armstrong said that there are robust efficacy data for the IL-17 inhibitors ixekizumab, secukinumab, and brodalumab in psoriasis and in the peripheral and axial forms of psoriatic arthritis (PsA). “Avoid using them in patients with a personal history of inflammatory bowel disease,” she advised.

Low rates of oral candidiasis have been reported in the literature, “but this has not been issue with our approved IL-17 inhibitors so far,” she said.

The IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and ustekinumab have robust data for psoriasis efficacy, she said, and three – guselkumab, risankizumab, and ustekinumab – are also approved for PsA. “These agents have the advantage of fewer injections, and the evidence [of efficacy] for IL-23 inhibitors continues to evolve, such as in patients with psoriatic arthritis involving the spine,” Dr. Armstrong said.

She also shared how she deals with patients who fail to respond to biologics. “Do you switch drugs, or do you dose escalate?” she asked. “In most cases, the strategy for dose escalation is to shorten the interval between the injections so the dosing is delivered more frequently.” In a case of primary failure, which Dr. Armstrong defined as a patient who has never responded optimally to a biologic, consider revisiting the diagnosis. “Maybe it’s cutaneous T-cell lymphoma or some other condition, because our current IL-17 and IL-23 medications work extremely well,” she said. “So, if you have a patient who is not responding at all, I would question the diagnosis and consider a biopsy.”

She generally waits about 6 months before switching a patient to another biologic, “to see if they’re one of the late bloomers who may catch up in efficacy,” she explained. “Switching the class of biologic is another consideration.”

If a patient had responded to the biologic for a long time and then lost response – known as secondary failure – Dr. Armstrong considers dose escalation or a switch to another agent within the same class “if it helps to address comorbidities such as PsA,” she said. “You can also try across-class switching.”

Dr. Armstrong disclosed ties with AbbVie, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Dermavant, EPI, Galderma, InCyte, Janssen, Leo, Lilly, Meiji, Modmed, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Suna, UCB, and Ventyx.

CARLSBAD, CALIF. – With 11 different biologics approved for the treatment of plaque psoriasis on the market, settling on which one to prescribe can be tricky.

“When you look at the list of options it can be confusing to many clinicians in deciding which one to choose,” April W. Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

Dr. Armstrong

One approach is to consider how the biologics compare in short- and long-term efficacy. “Several different meta-analyses of biologics have been conducted,” which include some head-to head studies, Dr. Armstrong said. “In terms of efficacy, [biologics] are similar at the population level,” she said.

In a meta-analysis of 71 randomized, controlled trials through July 2020, Dr. Armstrong and colleagues found that in the short-term, Psoriasis Area and Severity Index (PASI) 90 response rates at 10-16 weeks from baseline were highest for ixekizumab (72.9%), risankizumab (72.5%), and brodalumab (72%). These PASI 90 responses were significantly higher than among patients on guselkumab (65%), secukinumab (65%), infliximab (56.8%), certolizumab (400 mg: 49.6%; 200 mg: 42.2%), ustekinumab (90 mg: 47.9%; weight-based: 45.7%; 45 mg: 44.6%), adalimumab (43%), tildrakizumab (200 mg: 39.7%; 100 mg: 37.2%), etanercept (18.0%), apremilast (12.4%), and dimethyl fumarate (12.2%).

In a more recent meta-analysis, Dr. Armstrong and coauthors used area under the curve (AUC) analyses to compare the cumulative clinical benefits of biologics over 1 year. They found that the placebo-adjusted normalized maximum AUC for a PASI 100 response was greatest for ixekizumab (0.436), risankizumab (0.423), and brodalumab (0.378), followed by guselkumab (0.358), secukinumab (0.324), ustekinumab (0.201), adalimumab (0.183), and etanercept (0.087).

In Dr. Armstrong’s opinion, the tumor necrosis factor (TNF) inhibitors etanercept, infliximab, adalimumab, and certolizumab “have served their purpose for plaque psoriasis over time, but these days I would probably choose either an IL [interleukin]-17 inhibitor or an IL-23 inhibitor first,” she said. Still, TNF inhibitors “are certainly good for psoriatic arthritis, and certolizumab is appropriate for patients who are pregnant or breastfeeding,” she said. “Avoid them in patients with demyelinating disease and in those with hepatitis B. They are not preferred in patients with latent TB or advanced CHF.”

Dr. Armstrong said that there are robust efficacy data for the IL-17 inhibitors ixekizumab, secukinumab, and brodalumab in psoriasis and in the peripheral and axial forms of psoriatic arthritis (PsA). “Avoid using them in patients with a personal history of inflammatory bowel disease,” she advised.

Low rates of oral candidiasis have been reported in the literature, “but this has not been issue with our approved IL-17 inhibitors so far,” she said.

The IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and ustekinumab have robust data for psoriasis efficacy, she said, and three – guselkumab, risankizumab, and ustekinumab – are also approved for PsA. “These agents have the advantage of fewer injections, and the evidence [of efficacy] for IL-23 inhibitors continues to evolve, such as in patients with psoriatic arthritis involving the spine,” Dr. Armstrong said.

She also shared how she deals with patients who fail to respond to biologics. “Do you switch drugs, or do you dose escalate?” she asked. “In most cases, the strategy for dose escalation is to shorten the interval between the injections so the dosing is delivered more frequently.” In a case of primary failure, which Dr. Armstrong defined as a patient who has never responded optimally to a biologic, consider revisiting the diagnosis. “Maybe it’s cutaneous T-cell lymphoma or some other condition, because our current IL-17 and IL-23 medications work extremely well,” she said. “So, if you have a patient who is not responding at all, I would question the diagnosis and consider a biopsy.”

She generally waits about 6 months before switching a patient to another biologic, “to see if they’re one of the late bloomers who may catch up in efficacy,” she explained. “Switching the class of biologic is another consideration.”

If a patient had responded to the biologic for a long time and then lost response – known as secondary failure – Dr. Armstrong considers dose escalation or a switch to another agent within the same class “if it helps to address comorbidities such as PsA,” she said. “You can also try across-class switching.”

Dr. Armstrong disclosed ties with AbbVie, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Dermavant, EPI, Galderma, InCyte, Janssen, Leo, Lilly, Meiji, Modmed, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Suna, UCB, and Ventyx.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

A version of this article first appeared on Medscape.com.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

A version of this article first appeared on Medscape.com.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

A version of this article first appeared on Medscape.com.