Cardiology

A new study has determined a benefit of cardiac CT scans beyond assessing heart health: Evaluating fracture rate and potential osteoporosis through the bone mineral density (BMD) of thoracic vertebrae.

“Our results represent a step toward appraisal and recognition of the clinical utility of opportunistic BMD screening from cardiac CT,” wrote Josephine Therkildsen, MD, of Hospital Unit West in Herning, Denmark, and coauthors. The study was published July 14 in Radiology.

To determine if further analysis of cardiac CT could help determine BMD and its association with fracture rate, the investigators launched a prospective observational study of 1,487 Danish patients with potential coronary artery disease who underwent cardiac CT scans between September 2014 and March 2016. Their mean age was 57 years (standard deviation, 9; range, 40-80). Nearly all of the patients were white, and 52.5% (n = 781) were women.

All participants underwent a noncontrast-enhanced cardiac CT, from which volumetric BMD of three thoracic vertebrae was measured via commercially available semiautomatic software. Their mean BMD was 119 mg/cm³ (SD, 34) with no significant difference noted between male and female patients. Of the 1,487 participants, 695 were defined as having normal BMD (> 120 mg/cm³), 613 as having low BMD (80-120 mg/cm³), and 179 as having very low BMD (< 80 mg/cm³). Median follow-up was 3.1 years (interquartile range, 2.7-3.4).

Incident fracture occurred in 80 patients (5.4%), of whom 48 were women and 32 were men. Patients who suffered fractures were significantly older than patients with no fractures (mean 59 years vs. 57 years; P = .03). Of the 80 patients with fractures, 31 were osteoporosis related.

In an unadjusted analysis, participants with very low BMD had a greater rate of any fracture (hazard ratio [HR], 2.6; 95% confidence interval, 1.4-4.7; P = .002) and of osteoporosis-related fracture (HR, 8.1; 95% CI, 2.4-27.0; P = .001). After adjustment for age and sex, their rates remained significantly greater for any fracture (HR, 2.1; 95% CI, 1.1-4.2; P = .03) and for osteoporosis-related fracture (HR, 4.0; 95% CI, 1.1-15.0; P = .04).

“Opportunistic” use of scans benefits both physicians and patients

“The concept of using a CT scan that was done for a different purpose allows you to be opportunistic,” Ethel S. Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the department of medicine at Columbia University and director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center, New York–Presbyterian Hospital, New York, said in an interview. “If you’re dealing with older patients, and if you have the software for your radiologist to use to reanalyze the CT scan and say something about the bone, it’s certainly a way of estimating who may be at risk of future fractures.

“From a practical point of view, it’s hard to imagine that it would ever replace conventional bone mineral density testing via DXA [dual-energy x-ray absorptiometry],” she added. “That said, osteoporosis is woefully underdiagnosed because people don’t get DXA tested. This study showed that, if you have access to the scan of the thoracic or even the lumbar spine and if you have the necessary software, you can make legitimate statements about the numbers being low or very low. What that would lead to, I would hope, is some internists to say, ‘This could be a predictor of fracture risk. We should put you on treatment.’ And then follow up with a conventional DXA test.

“Is that going to happen? I don’t know. But the bottom line of the study is: Anything that may enhance the physician’s drive to evaluate a patient for fracture risk is good.”
 

Whatever the reason for the scan, CT can help diagnose osteoporosis

This study reinforces that CT exams – of the chest, in particular – can serve a valuable dual purpose as osteoporosis screenings, Miriam A. Bredella, MD, professor of radiology at Harvard Medical School and vice chair of the department of radiology at Massachusetts General Hospital, Boston, wrote in an accompanying editorial.

“In the United States, more than 80 million CT examinations are performed each year, many of which could be used to screen for osteoporosis without additional costs or radiation exposure,” she wrote. And thanks to the findings of the study by Therkildsen et al., which relied on both established and new BMD thresholds, the link between thoracic spine BMD and fracture risk is clearer than ever.

“I hope this study will ignite interest in using chest CT examinations performed for other purposes, such as lung cancer screening, for opportunistic osteoporosis screening and prediction of fractures in vulnerable populations,” she added.

The authors acknowledged their study’s limitations, including a small number of fracture events overall and the inability to evaluate associations between BMD and fracture rate at specific locations. In addition, their cohort was largely made up of white participants with a certain coronary artery disease risk profile; because of ethnical differences in BMD measurements, their results “cannot be extrapolated to other ethnical groups.”

Several of the study’s authors reported potential conflicts of interest, including receiving grants and money for consultancies and board memberships from various councils, associations, and pharmaceutical companies. Dr. Bredella reported no conflicts of interest. Dr. Siris has no relevant disclosures.

SOURCE: Therkildsen J et al. Radiology. 2020 Jul 14. doi: 10.1148/radiol.2020192706.

A new study has determined a benefit of cardiac CT scans beyond assessing heart health: Evaluating fracture rate and potential osteoporosis through the bone mineral density (BMD) of thoracic vertebrae.

“Our results represent a step toward appraisal and recognition of the clinical utility of opportunistic BMD screening from cardiac CT,” wrote Josephine Therkildsen, MD, of Hospital Unit West in Herning, Denmark, and coauthors. The study was published July 14 in Radiology.

To determine if further analysis of cardiac CT could help determine BMD and its association with fracture rate, the investigators launched a prospective observational study of 1,487 Danish patients with potential coronary artery disease who underwent cardiac CT scans between September 2014 and March 2016. Their mean age was 57 years (standard deviation, 9; range, 40-80). Nearly all of the patients were white, and 52.5% (n = 781) were women.

All participants underwent a noncontrast-enhanced cardiac CT, from which volumetric BMD of three thoracic vertebrae was measured via commercially available semiautomatic software. Their mean BMD was 119 mg/cm³ (SD, 34) with no significant difference noted between male and female patients. Of the 1,487 participants, 695 were defined as having normal BMD (> 120 mg/cm³), 613 as having low BMD (80-120 mg/cm³), and 179 as having very low BMD (< 80 mg/cm³). Median follow-up was 3.1 years (interquartile range, 2.7-3.4).

Incident fracture occurred in 80 patients (5.4%), of whom 48 were women and 32 were men. Patients who suffered fractures were significantly older than patients with no fractures (mean 59 years vs. 57 years; P = .03). Of the 80 patients with fractures, 31 were osteoporosis related.

In an unadjusted analysis, participants with very low BMD had a greater rate of any fracture (hazard ratio [HR], 2.6; 95% confidence interval, 1.4-4.7; P = .002) and of osteoporosis-related fracture (HR, 8.1; 95% CI, 2.4-27.0; P = .001). After adjustment for age and sex, their rates remained significantly greater for any fracture (HR, 2.1; 95% CI, 1.1-4.2; P = .03) and for osteoporosis-related fracture (HR, 4.0; 95% CI, 1.1-15.0; P = .04).

“Opportunistic” use of scans benefits both physicians and patients

“The concept of using a CT scan that was done for a different purpose allows you to be opportunistic,” Ethel S. Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the department of medicine at Columbia University and director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center, New York–Presbyterian Hospital, New York, said in an interview. “If you’re dealing with older patients, and if you have the software for your radiologist to use to reanalyze the CT scan and say something about the bone, it’s certainly a way of estimating who may be at risk of future fractures.

“From a practical point of view, it’s hard to imagine that it would ever replace conventional bone mineral density testing via DXA [dual-energy x-ray absorptiometry],” she added. “That said, osteoporosis is woefully underdiagnosed because people don’t get DXA tested. This study showed that, if you have access to the scan of the thoracic or even the lumbar spine and if you have the necessary software, you can make legitimate statements about the numbers being low or very low. What that would lead to, I would hope, is some internists to say, ‘This could be a predictor of fracture risk. We should put you on treatment.’ And then follow up with a conventional DXA test.

“Is that going to happen? I don’t know. But the bottom line of the study is: Anything that may enhance the physician’s drive to evaluate a patient for fracture risk is good.”
 

Whatever the reason for the scan, CT can help diagnose osteoporosis

This study reinforces that CT exams – of the chest, in particular – can serve a valuable dual purpose as osteoporosis screenings, Miriam A. Bredella, MD, professor of radiology at Harvard Medical School and vice chair of the department of radiology at Massachusetts General Hospital, Boston, wrote in an accompanying editorial.

“In the United States, more than 80 million CT examinations are performed each year, many of which could be used to screen for osteoporosis without additional costs or radiation exposure,” she wrote. And thanks to the findings of the study by Therkildsen et al., which relied on both established and new BMD thresholds, the link between thoracic spine BMD and fracture risk is clearer than ever.

“I hope this study will ignite interest in using chest CT examinations performed for other purposes, such as lung cancer screening, for opportunistic osteoporosis screening and prediction of fractures in vulnerable populations,” she added.

The authors acknowledged their study’s limitations, including a small number of fracture events overall and the inability to evaluate associations between BMD and fracture rate at specific locations. In addition, their cohort was largely made up of white participants with a certain coronary artery disease risk profile; because of ethnical differences in BMD measurements, their results “cannot be extrapolated to other ethnical groups.”

Several of the study’s authors reported potential conflicts of interest, including receiving grants and money for consultancies and board memberships from various councils, associations, and pharmaceutical companies. Dr. Bredella reported no conflicts of interest. Dr. Siris has no relevant disclosures.

SOURCE: Therkildsen J et al. Radiology. 2020 Jul 14. doi: 10.1148/radiol.2020192706.

A new study has determined a benefit of cardiac CT scans beyond assessing heart health: Evaluating fracture rate and potential osteoporosis through the bone mineral density (BMD) of thoracic vertebrae.

“Our results represent a step toward appraisal and recognition of the clinical utility of opportunistic BMD screening from cardiac CT,” wrote Josephine Therkildsen, MD, of Hospital Unit West in Herning, Denmark, and coauthors. The study was published July 14 in Radiology.

To determine if further analysis of cardiac CT could help determine BMD and its association with fracture rate, the investigators launched a prospective observational study of 1,487 Danish patients with potential coronary artery disease who underwent cardiac CT scans between September 2014 and March 2016. Their mean age was 57 years (standard deviation, 9; range, 40-80). Nearly all of the patients were white, and 52.5% (n = 781) were women.

All participants underwent a noncontrast-enhanced cardiac CT, from which volumetric BMD of three thoracic vertebrae was measured via commercially available semiautomatic software. Their mean BMD was 119 mg/cm³ (SD, 34) with no significant difference noted between male and female patients. Of the 1,487 participants, 695 were defined as having normal BMD (> 120 mg/cm³), 613 as having low BMD (80-120 mg/cm³), and 179 as having very low BMD (< 80 mg/cm³). Median follow-up was 3.1 years (interquartile range, 2.7-3.4).

Incident fracture occurred in 80 patients (5.4%), of whom 48 were women and 32 were men. Patients who suffered fractures were significantly older than patients with no fractures (mean 59 years vs. 57 years; P = .03). Of the 80 patients with fractures, 31 were osteoporosis related.

In an unadjusted analysis, participants with very low BMD had a greater rate of any fracture (hazard ratio [HR], 2.6; 95% confidence interval, 1.4-4.7; P = .002) and of osteoporosis-related fracture (HR, 8.1; 95% CI, 2.4-27.0; P = .001). After adjustment for age and sex, their rates remained significantly greater for any fracture (HR, 2.1; 95% CI, 1.1-4.2; P = .03) and for osteoporosis-related fracture (HR, 4.0; 95% CI, 1.1-15.0; P = .04).

“Opportunistic” use of scans benefits both physicians and patients

“The concept of using a CT scan that was done for a different purpose allows you to be opportunistic,” Ethel S. Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the department of medicine at Columbia University and director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center, New York–Presbyterian Hospital, New York, said in an interview. “If you’re dealing with older patients, and if you have the software for your radiologist to use to reanalyze the CT scan and say something about the bone, it’s certainly a way of estimating who may be at risk of future fractures.

“From a practical point of view, it’s hard to imagine that it would ever replace conventional bone mineral density testing via DXA [dual-energy x-ray absorptiometry],” she added. “That said, osteoporosis is woefully underdiagnosed because people don’t get DXA tested. This study showed that, if you have access to the scan of the thoracic or even the lumbar spine and if you have the necessary software, you can make legitimate statements about the numbers being low or very low. What that would lead to, I would hope, is some internists to say, ‘This could be a predictor of fracture risk. We should put you on treatment.’ And then follow up with a conventional DXA test.

“Is that going to happen? I don’t know. But the bottom line of the study is: Anything that may enhance the physician’s drive to evaluate a patient for fracture risk is good.”
 

Whatever the reason for the scan, CT can help diagnose osteoporosis

This study reinforces that CT exams – of the chest, in particular – can serve a valuable dual purpose as osteoporosis screenings, Miriam A. Bredella, MD, professor of radiology at Harvard Medical School and vice chair of the department of radiology at Massachusetts General Hospital, Boston, wrote in an accompanying editorial.

“In the United States, more than 80 million CT examinations are performed each year, many of which could be used to screen for osteoporosis without additional costs or radiation exposure,” she wrote. And thanks to the findings of the study by Therkildsen et al., which relied on both established and new BMD thresholds, the link between thoracic spine BMD and fracture risk is clearer than ever.

“I hope this study will ignite interest in using chest CT examinations performed for other purposes, such as lung cancer screening, for opportunistic osteoporosis screening and prediction of fractures in vulnerable populations,” she added.

The authors acknowledged their study’s limitations, including a small number of fracture events overall and the inability to evaluate associations between BMD and fracture rate at specific locations. In addition, their cohort was largely made up of white participants with a certain coronary artery disease risk profile; because of ethnical differences in BMD measurements, their results “cannot be extrapolated to other ethnical groups.”

Several of the study’s authors reported potential conflicts of interest, including receiving grants and money for consultancies and board memberships from various councils, associations, and pharmaceutical companies. Dr. Bredella reported no conflicts of interest. Dr. Siris has no relevant disclosures.

SOURCE: Therkildsen J et al. Radiology. 2020 Jul 14. doi: 10.1148/radiol.2020192706.

A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.

The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks, compared with Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.

The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions,with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York.

In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks, compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.

“Improving health care and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“But this won’t happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all health care providers,” he said. “Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients,” but “most prior studies in this regard have looked at population-based data.”

In contrast, the current study used hospital source records – which are considered more accurate than administrative databases – and event coding reports, Dr. Stone said, plus angiographic core laboratory analyses for all patients, which allows “an independent assessment of the extent and type of coronary artery disease and procedural outcomes.”

The analysis “demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race,” Michael Nanna, MD, said in an interview.

The “troubling” results “highlight the persistence of racial disparities in health care and the need to renew our focus on closing these gaps [and] is yet another call to action for clinicians, researchers, and the health care system at large,” said Dr. Nanna, of Duke University Medical Center, Durham, N.C., and lead author on an editorial accompanying the published analysis.

Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, 9 were stent comparisons and 1 compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors noted. The median follow-up was about 1,100 days.

White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% – figures that “confirm the well-known fact that minority groups are underrepresented in clinical trials,” Dr. Stone said.

There were notable demographic and clinical differences at baseline between the four groups.

For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male, compared with White patients.

Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index, compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences). Hispanics were more likely to have ACS at baseline, compared with Whites, and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD (about 32% of each) and ACS (about 68% in both cases). Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference). In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks, compared with Whites (hazard ratio, 1.28; 95% CI, 1.05-1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15-2.09; P = .004). At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26-3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01-2.10; P = .045), compared with Whites.

No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians, compared with Whites.

Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.

Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes “should have been accounted for when the researchers adjusted for these clinical phenotypes,” the editorial notes.

Some of the difference in risk must have derived from uncontrolled-for variables, and “[b]eyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes,” the editorialists wrote.

The adjusted analysis, noted Golomb et al, suggests “that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors.”

As such, they agreed: “The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors.”

Dr. Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.

“Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes” may also be involved.

“Achieving representative proportions of minorities in clinical trials is essential but has proved challenging,” Dr. Stone said. “We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies.”

Dr. Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.

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

A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.

The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks, compared with Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.

The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions,with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York.

In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks, compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.

“Improving health care and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“But this won’t happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all health care providers,” he said. “Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients,” but “most prior studies in this regard have looked at population-based data.”

In contrast, the current study used hospital source records – which are considered more accurate than administrative databases – and event coding reports, Dr. Stone said, plus angiographic core laboratory analyses for all patients, which allows “an independent assessment of the extent and type of coronary artery disease and procedural outcomes.”

The analysis “demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race,” Michael Nanna, MD, said in an interview.

The “troubling” results “highlight the persistence of racial disparities in health care and the need to renew our focus on closing these gaps [and] is yet another call to action for clinicians, researchers, and the health care system at large,” said Dr. Nanna, of Duke University Medical Center, Durham, N.C., and lead author on an editorial accompanying the published analysis.

Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, 9 were stent comparisons and 1 compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors noted. The median follow-up was about 1,100 days.

White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% – figures that “confirm the well-known fact that minority groups are underrepresented in clinical trials,” Dr. Stone said.

There were notable demographic and clinical differences at baseline between the four groups.

For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male, compared with White patients.

Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index, compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences). Hispanics were more likely to have ACS at baseline, compared with Whites, and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD (about 32% of each) and ACS (about 68% in both cases). Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference). In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks, compared with Whites (hazard ratio, 1.28; 95% CI, 1.05-1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15-2.09; P = .004). At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26-3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01-2.10; P = .045), compared with Whites.

No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians, compared with Whites.

Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.

Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes “should have been accounted for when the researchers adjusted for these clinical phenotypes,” the editorial notes.

Some of the difference in risk must have derived from uncontrolled-for variables, and “[b]eyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes,” the editorialists wrote.

The adjusted analysis, noted Golomb et al, suggests “that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors.”

As such, they agreed: “The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors.”

Dr. Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.

“Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes” may also be involved.

“Achieving representative proportions of minorities in clinical trials is essential but has proved challenging,” Dr. Stone said. “We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies.”

Dr. Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.

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

A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.

The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks, compared with Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.

The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions,with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York.

In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks, compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.

“Improving health care and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“But this won’t happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all health care providers,” he said. “Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients,” but “most prior studies in this regard have looked at population-based data.”

In contrast, the current study used hospital source records – which are considered more accurate than administrative databases – and event coding reports, Dr. Stone said, plus angiographic core laboratory analyses for all patients, which allows “an independent assessment of the extent and type of coronary artery disease and procedural outcomes.”

The analysis “demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race,” Michael Nanna, MD, said in an interview.

The “troubling” results “highlight the persistence of racial disparities in health care and the need to renew our focus on closing these gaps [and] is yet another call to action for clinicians, researchers, and the health care system at large,” said Dr. Nanna, of Duke University Medical Center, Durham, N.C., and lead author on an editorial accompanying the published analysis.

Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, 9 were stent comparisons and 1 compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors noted. The median follow-up was about 1,100 days.

White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% – figures that “confirm the well-known fact that minority groups are underrepresented in clinical trials,” Dr. Stone said.

There were notable demographic and clinical differences at baseline between the four groups.

For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male, compared with White patients.

Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index, compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences). Hispanics were more likely to have ACS at baseline, compared with Whites, and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD (about 32% of each) and ACS (about 68% in both cases). Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference). In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks, compared with Whites (hazard ratio, 1.28; 95% CI, 1.05-1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15-2.09; P = .004). At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26-3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01-2.10; P = .045), compared with Whites.

No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians, compared with Whites.

Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.

Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes “should have been accounted for when the researchers adjusted for these clinical phenotypes,” the editorial notes.

Some of the difference in risk must have derived from uncontrolled-for variables, and “[b]eyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes,” the editorialists wrote.

The adjusted analysis, noted Golomb et al, suggests “that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors.”

As such, they agreed: “The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors.”

Dr. Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.

“Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes” may also be involved.

“Achieving representative proportions of minorities in clinical trials is essential but has proved challenging,” Dr. Stone said. “We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies.”

Dr. Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.

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

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

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

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

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

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

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

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

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

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

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

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Patients with interstitial lung disease–associated pulmonary hypertension who were treated with inhaled treprostinil (Tyvaso) had significantly greater improvement in exercise capacity over 16 weeks, compared with patients who used a placebo inhaler, results of a phase 3 trial showed.

Among 326 patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD), those who were randomly assigned to treatment with treprostinil had a placebo-corrected median difference from baseline in 6-minute walk distance of 21 m (P = .004), reported Steven D. Nathan, MD, from Inova Fairfax Hospital in Falls Church, Va., on behalf of coinvestigators in the INCREASE study (NCT02630316).

“These results support an additional treatment avenue, and might herald a shift in the clinical management of patients with interstitial lung disease,” he said in the American Thoracic Society’s virtual clinical trial session.

“This was an outstanding presentation and outstanding results. I personally am very excited, because this is a field where I work,” commented Martin Kolb, MD, PhD, from McMaster University, Hamilton, Ont., the facilitator for the online presentation.

The INCREASE trial compared inhaled treprostinil dose four times daily with placebo in patients with a CT scan–confirmed diagnosis of World Health Organization group 3 PH within 6 months before randomization who had evidence of diffuse parenchymal lung disease. Eligible patients could have any form of ILD or combined pulmonary fibrosis and emphysema.

Key inclusion criteria included right-heart catheterization within the previous year with documented pulmonary vascular resistance greater than 3 Wood units, pulmonary capillary wedge pressure 15 mm Hg or less, and mean pulmonary arterial pressure 25 mm Hg or higher.

Patients also had to have a 6-minute walk distance of at least 100 m and have stable disease while on an optimized dose of medications for underlying lung disease. Patients with group 3 connective tissue disease had to have baseline forced vital capacity of less than 70%.

The final study cohorts included patients with idiopathic interstitial pneumonias, chronic hypersensitivity pneumonitis, connective tissue disease, combined pulmonary fibrosis and emphysema, and occupational lung disease.

The patients were randomized to receive either inhaled treprostinil at a starting dose of 6 mcg/breath four times daily or to placebo (163 patients in each arm). All patients started the study drug at a dose of three breaths four times daily during waking hours. Dose escalations – adding 1 additional breath four times daily – were allowed every 3 days, up to a target dose of 9 breaths (54 mcg) four times daily, and a maximum of 12 breaths (72 mcg) four times daily as clinically tolerated.

A total of 130 patients assigned to treprostinil and 128 assigned to placebo completed 16 weeks of therapy and assessment.

As noted before, patients assigned to treprostinil had a placebo-corrected median difference from baseline in peak 6-minute walk distance, as measured by Hodges-Lehmann estimation, of 21 m (P = .004). An analysis of the same parameter using mixed model repeated measurement showed a placebo-corrected difference from baseline in peak 6-minute walk distance of 31.12 m (P < .001).

Secondary endpoints that were significantly better with treprostinil, compared with placebo, included improvements in N-terminal of the prohormone brain natriuretic peptide, a longer time to clinical worsening, and improvements in peak 6-minute walk distance week 12, and trough 6-minute walk distance at week 15.

Treprostinil was associated with a 39% reduction in risk of clinical worsening (P = .04). In all, 37 patients on treprostinil (22.7%) and 54 on placebo (33.1%) experienced clinical worsening.

For the exploratory endpoints of change in patient reported quality of life as measured by the St. George’s Respiratory Questionnaire, or in peak distance saturation product, however, there were no significant differences between the groups.

In addition, treprostinil was associated with a 34% reduction the risk of exacerbation of underlying lung disease, compared with placebo (P = .03).

The safety profile of treprostinil was similar to that seen in other studies of the drug, and most treatment-related adverse events were mild or moderate in severity. Adverse events led to discontinuation in 10% of patients on treprostinil and 8% on placebo.

Serious adverse events were seen in 23.3% and 25.8%, respectively. The most frequently occurring adverse events of any grade included cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea, throat irritation, and oropharyngeal pain.

There was no evidence of worsened oxygenation or lung function “allaying V/Q mismatch concerns,” Dr. Nathan said, and there was evidence for an improvement in forced vital capacity with treprostinil.

In the question-and-answer portion of the presentation, Dr. Kolb commented that many clinicians, particularly those who treated patients with ILD, question whether a 21-m difference in walk distance makes much of a difference in patient lives. He relayed a question from a viewer asking how Dr. Nathan and associates reconciled their primary endpoint with the finding that there was no difference in patient-reported quality of life.

“I think that the difference in the 6-minute walk test was both statistically significant and clinically meaningful,” Dr. Nathan replied.

He noted that the primary endpoint used a stringent measure, and that less conservative methods of analysis showed a larger difference in benefit favoring treprostinil. He also pointed out that the original study of inhaled treprostinil added to oral therapy for pulmonary arterial hypertension showed a 20-m improvement in walk distance, and that these results were sufficient to get the inhaled formulation approved in the United States (J Am Coll Cardiol. 2010 May. doi: 10.1016/j.jacc.2010.01.027).

Regarding the failure to detect a difference in quality of life, he said that the study was only 16 weeks in length, and that the St. George’s Respiratory Questionnaire was developed for evaluation of patients with chronic obstructive pulmonary disease, “perhaps not the best instrument to use in an ILD PH study.”

The study was funded by United Therapeutics. Dr. Nathan disclosed advisory committee activity/consulting, research support, and speaker fees from the company. Dr. Kolb has previously disclosed financial relationships with various companies, not including United Therapeutics.

Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than that of other ACE inhibitors or angiotensin receptor blockers (ARBs) and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests.

The study was published online in the Journal of the American Pharmacists Association.

The authors, led by Emma G. Stafford, PharmD, University of Missouri-Kansas City School of Pharmacy, note that diabetes seems to confer a higher risk of adverse outcomes in COVID-19 infection and there is conflicting data on the contribution of ACE inhibitors and ARBs, commonly used medications in diabetes, on the mortality and morbidity of COVID-19.

“In light of the recent COVID-19 outbreak, more research is needed to understand the effects that diabetes (and its medications) may have on the respiratory system and how that could affect the management of diseases such as COVID-19,” they say.

“Although ACE inhibitors and ARBs are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts,” they add.

For the current study, the researchers analyzed data from multiple publicly available data sources on adverse drug reactions in patients with diabetes taking ACE inhibitors or ARBs. The data included all adverse drug events (ADEs) reported nationally to the US Food and Drug Administration and internationally to the Medical Dictionary for Regulatory Activities (MedDRA).

Results showed that captopril, the first ACE inhibitor approved back in 1981, has a higher incidence of pulmonary ADEs in patients with diabetes as compared with other ACE-inhibitor drugs (P = .005) as well as a statistically significant difference in pulmonary events compared with ARBs (P = .012).

“These analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19,” the authors conclude.

They say that the high incidence of pulmonary adverse drug effects with captopril “highlights the fact that the drugs belonging in one class are not identical and that its pharmacokinetics and pharmacodynamics can affect the patients’ health especially during acute processes like COVID-19.”

“This is especially important as current observational studies of COVID-19 patients tend to group drugs within a class and are not analyzing the potential differences within each class,” they add.

They note that ACE inhibitors can be broadly classified into 3 structural classes: sulfhydryl-, dicarboxyl-, and phosphorous- containing molecules. Notably, captopril is the only currently available ACE inhibitor belonging to the sulfhydryl-containing class and may explain the higher incidence of adverse drug effects observed, they comment.

“Health care providers have been left with many questions when treating patients with COVID-19, including how ACE inhibitors or ARBs may affect their clinical course. Results from this study may be helpful when prescribing or continuing ACE inhibitors or ARBs for patients with diabetes and infections or illnesses that may affect pulmonary function, such as COVID-19,” they conclude.

Questioning safety in COVID-19 an “overreach”

Commenting for Medscape Medical News, Michael A. Weber, MD, professor of medicine at State University of New York, said he thought the current article appears to overreach in questioning captopril’s safety in the COVID-19 setting.

“Captopril was the first ACE inhibitor available for clinical use. In early prescribing its dosage was not well understood and it might have been administered in excessive amounts,” Weber notes.

“There were some renal and other adverse effects reported that at first were attributed to the fact that captopril, unlike any other popular ACE inhibitors, contained a sulfhydryl (SH) group in its molecule,” he said. “It is not clear whether this feature could be responsible for the increased pulmonary side effects and potential danger to COVID-19 patients now reported with captopril in this new pharmacy article.”

But he adds: “The article contains no evidence that the effect of captopril or any other ACE inhibitor on the pulmonary ACE-2 enzyme has a deleterious effect on outcomes of COVID-19 disease. In any case, captopril — which should be prescribed in a twice-daily dose — is not frequently prescribed these days since newer ACE inhibitors are effective with just once-daily dosing.”

This article first appeared on Medscape.com.

Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than that of other ACE inhibitors or angiotensin receptor blockers (ARBs) and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests.

The study was published online in the Journal of the American Pharmacists Association.

The authors, led by Emma G. Stafford, PharmD, University of Missouri-Kansas City School of Pharmacy, note that diabetes seems to confer a higher risk of adverse outcomes in COVID-19 infection and there is conflicting data on the contribution of ACE inhibitors and ARBs, commonly used medications in diabetes, on the mortality and morbidity of COVID-19.

“In light of the recent COVID-19 outbreak, more research is needed to understand the effects that diabetes (and its medications) may have on the respiratory system and how that could affect the management of diseases such as COVID-19,” they say.

“Although ACE inhibitors and ARBs are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts,” they add.

For the current study, the researchers analyzed data from multiple publicly available data sources on adverse drug reactions in patients with diabetes taking ACE inhibitors or ARBs. The data included all adverse drug events (ADEs) reported nationally to the US Food and Drug Administration and internationally to the Medical Dictionary for Regulatory Activities (MedDRA).

Results showed that captopril, the first ACE inhibitor approved back in 1981, has a higher incidence of pulmonary ADEs in patients with diabetes as compared with other ACE-inhibitor drugs (P = .005) as well as a statistically significant difference in pulmonary events compared with ARBs (P = .012).

“These analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19,” the authors conclude.

They say that the high incidence of pulmonary adverse drug effects with captopril “highlights the fact that the drugs belonging in one class are not identical and that its pharmacokinetics and pharmacodynamics can affect the patients’ health especially during acute processes like COVID-19.”

“This is especially important as current observational studies of COVID-19 patients tend to group drugs within a class and are not analyzing the potential differences within each class,” they add.

They note that ACE inhibitors can be broadly classified into 3 structural classes: sulfhydryl-, dicarboxyl-, and phosphorous- containing molecules. Notably, captopril is the only currently available ACE inhibitor belonging to the sulfhydryl-containing class and may explain the higher incidence of adverse drug effects observed, they comment.

“Health care providers have been left with many questions when treating patients with COVID-19, including how ACE inhibitors or ARBs may affect their clinical course. Results from this study may be helpful when prescribing or continuing ACE inhibitors or ARBs for patients with diabetes and infections or illnesses that may affect pulmonary function, such as COVID-19,” they conclude.

Questioning safety in COVID-19 an “overreach”

Commenting for Medscape Medical News, Michael A. Weber, MD, professor of medicine at State University of New York, said he thought the current article appears to overreach in questioning captopril’s safety in the COVID-19 setting.

“Captopril was the first ACE inhibitor available for clinical use. In early prescribing its dosage was not well understood and it might have been administered in excessive amounts,” Weber notes.

“There were some renal and other adverse effects reported that at first were attributed to the fact that captopril, unlike any other popular ACE inhibitors, contained a sulfhydryl (SH) group in its molecule,” he said. “It is not clear whether this feature could be responsible for the increased pulmonary side effects and potential danger to COVID-19 patients now reported with captopril in this new pharmacy article.”

But he adds: “The article contains no evidence that the effect of captopril or any other ACE inhibitor on the pulmonary ACE-2 enzyme has a deleterious effect on outcomes of COVID-19 disease. In any case, captopril — which should be prescribed in a twice-daily dose — is not frequently prescribed these days since newer ACE inhibitors are effective with just once-daily dosing.”

This article first appeared on Medscape.com.

Captopril appears to be associated with a higher rate of pulmonary adverse reactions in patients with diabetes than that of other ACE inhibitors or angiotensin receptor blockers (ARBs) and therefore may not be the best choice for patients with diabetes and COVID-19, a new study suggests.

The study was published online in the Journal of the American Pharmacists Association.

The authors, led by Emma G. Stafford, PharmD, University of Missouri-Kansas City School of Pharmacy, note that diabetes seems to confer a higher risk of adverse outcomes in COVID-19 infection and there is conflicting data on the contribution of ACE inhibitors and ARBs, commonly used medications in diabetes, on the mortality and morbidity of COVID-19.

“In light of the recent COVID-19 outbreak, more research is needed to understand the effects that diabetes (and its medications) may have on the respiratory system and how that could affect the management of diseases such as COVID-19,” they say.

“Although ACE inhibitors and ARBs are generally considered to have similar adverse event profiles, evaluation of postmarketing adverse events may shed light on minute differences that could have important clinical impacts,” they add.

For the current study, the researchers analyzed data from multiple publicly available data sources on adverse drug reactions in patients with diabetes taking ACE inhibitors or ARBs. The data included all adverse drug events (ADEs) reported nationally to the US Food and Drug Administration and internationally to the Medical Dictionary for Regulatory Activities (MedDRA).

Results showed that captopril, the first ACE inhibitor approved back in 1981, has a higher incidence of pulmonary ADEs in patients with diabetes as compared with other ACE-inhibitor drugs (P = .005) as well as a statistically significant difference in pulmonary events compared with ARBs (P = .012).

“These analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19,” the authors conclude.

They say that the high incidence of pulmonary adverse drug effects with captopril “highlights the fact that the drugs belonging in one class are not identical and that its pharmacokinetics and pharmacodynamics can affect the patients’ health especially during acute processes like COVID-19.”

“This is especially important as current observational studies of COVID-19 patients tend to group drugs within a class and are not analyzing the potential differences within each class,” they add.

They note that ACE inhibitors can be broadly classified into 3 structural classes: sulfhydryl-, dicarboxyl-, and phosphorous- containing molecules. Notably, captopril is the only currently available ACE inhibitor belonging to the sulfhydryl-containing class and may explain the higher incidence of adverse drug effects observed, they comment.

“Health care providers have been left with many questions when treating patients with COVID-19, including how ACE inhibitors or ARBs may affect their clinical course. Results from this study may be helpful when prescribing or continuing ACE inhibitors or ARBs for patients with diabetes and infections or illnesses that may affect pulmonary function, such as COVID-19,” they conclude.

Questioning safety in COVID-19 an “overreach”

Commenting for Medscape Medical News, Michael A. Weber, MD, professor of medicine at State University of New York, said he thought the current article appears to overreach in questioning captopril’s safety in the COVID-19 setting.

“Captopril was the first ACE inhibitor available for clinical use. In early prescribing its dosage was not well understood and it might have been administered in excessive amounts,” Weber notes.

“There were some renal and other adverse effects reported that at first were attributed to the fact that captopril, unlike any other popular ACE inhibitors, contained a sulfhydryl (SH) group in its molecule,” he said. “It is not clear whether this feature could be responsible for the increased pulmonary side effects and potential danger to COVID-19 patients now reported with captopril in this new pharmacy article.”

But he adds: “The article contains no evidence that the effect of captopril or any other ACE inhibitor on the pulmonary ACE-2 enzyme has a deleterious effect on outcomes of COVID-19 disease. In any case, captopril — which should be prescribed in a twice-daily dose — is not frequently prescribed these days since newer ACE inhibitors are effective with just once-daily dosing.”

This article first appeared on Medscape.com.

Self-measured blood pressure (SMBP) monitoring at home is a validated approach to measure out-of-office BP that has the potential to improve the detection and control of hypertension, according to a joint policy statement from the American Heart Association (AHA) and American Medical Association (AMA).

“With fewer patients visiting medical offices during the COVID-19 pandemic, SMBP monitoring is more important than ever for people at risk for hypertension and uncontrolled BP,” writing group chair Daichi Shimbo, MD, said in a statement.

“There should be investment in creating and supporting the infrastructure for expanding self-measured BP monitoring, as well as increasing coverage for patient- and provider-related costs,” Dr. Shimbo, director, The Columbia Hypertension Center, Columbia University Irving Medical Center, New York, said in an interview.

The statement, Self-Measured Blood Pressure Monitoring at Home, was published June 22 in Circulation.

It provides “contemporary information” on the use, efficacy, and cost-effectiveness of SMBP at home for the diagnosis and management of hypertension.

The writing group noted that hypertension is one of the most important risk factors for cardiovascular disease. Several American and international guidelines support the use of SMBP.

“Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension,” the group pointed out.

Use validated devices

Devices that are validated for clinical accuracy should be used for SMBP monitoring, the writing group advised. Validated devices that use the oscillometric method are preferred, and a standardized BP measurement (with appropriately sized cuffs) and monitoring protocol should be followed.

The group noted that meta-analyses of randomized trials indicate that SMBP monitoring is associated with a reduction in BP and improved BP control, and the benefits are greatest when it is used along with other interventions, such as education and counseling, that can be delivered via phone or telehealth visits by nurses and care coordinators.

There are “sufficient data” to indicate that adding SMBP monitoring to office-based monitoring is cost-effective compared with office BP monitoring alone or usual care in patients with high office BP, the writing group said.

Potential cost savings associated with SMBP monitoring include a reduction in office visit follow-ups as a result of improved BP control, avoidance of possible overtreatment in patients with white-coat hypertension, and improvement in quality of life.

They noted that randomized controlled trials assessing the impact of SMBP monitoring on cardiovascular outcomes are needed.

Barriers to widespread use

The use of SMBP monitoring is “essential” for the self-management of hypertension and has “great appeal” for expanding the benefits of cardiovascular prevention, the writing group said. They acknowledged, however, that transitioning from solely office-based BP management to a strategy that includes SMBP monitoring is not without actual and potential barriers.

The group recommends addressing these barriers by:

• Educating patients and providers about the benefits of SMBP monitoring and the optimal approaches for SMBP monitoring.
• Establishing clinical core competency criteria to ensure high-quality SMBP monitoring is supported in clinical practice.
• Incorporating cointerventions that increase the effectiveness of SMBP monitoring, including behavioral change management and counseling, communication of treatment recommendations back to patients, medication management, and prescription and adherence monitoring.
• Creating systems for SMBP readings to be transferred from devices to electronic health records.
• Improving public and private health insurance coverage of validated SMBP monitoring devices prescribed by a health care provider.
• Reimbursing providers for costs associated with training patients, transmitting BP data, interpreting and reporting BP readings, and delivering cointerventions.

Increasing the use of SMBP monitoring is a major focus area of Target: BP – a national initiative of the AHA and AMA launched in response to the high prevalence of uncontrolled BP.

Target: BP helps health care organizations and care teams improve BP control rates through the evidence-based MAP BP Program.

MAP is an acronym that stands for Measure BP accurately every time it’s measured, Act rapidly to manage uncontrolled BP, and Partner with patients to promote BP self-management.

This research had no commercial funding. Dr. Shimbo has disclosed no relevant conflicts of interest. A complete list of disclosures for the writing group is available with the original article.
 

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

Self-measured blood pressure (SMBP) monitoring at home is a validated approach to measure out-of-office BP that has the potential to improve the detection and control of hypertension, according to a joint policy statement from the American Heart Association (AHA) and American Medical Association (AMA).

“With fewer patients visiting medical offices during the COVID-19 pandemic, SMBP monitoring is more important than ever for people at risk for hypertension and uncontrolled BP,” writing group chair Daichi Shimbo, MD, said in a statement.

“There should be investment in creating and supporting the infrastructure for expanding self-measured BP monitoring, as well as increasing coverage for patient- and provider-related costs,” Dr. Shimbo, director, The Columbia Hypertension Center, Columbia University Irving Medical Center, New York, said in an interview.

The statement, Self-Measured Blood Pressure Monitoring at Home, was published June 22 in Circulation.

It provides “contemporary information” on the use, efficacy, and cost-effectiveness of SMBP at home for the diagnosis and management of hypertension.

The writing group noted that hypertension is one of the most important risk factors for cardiovascular disease. Several American and international guidelines support the use of SMBP.

“Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension,” the group pointed out.

Use validated devices

Devices that are validated for clinical accuracy should be used for SMBP monitoring, the writing group advised. Validated devices that use the oscillometric method are preferred, and a standardized BP measurement (with appropriately sized cuffs) and monitoring protocol should be followed.

The group noted that meta-analyses of randomized trials indicate that SMBP monitoring is associated with a reduction in BP and improved BP control, and the benefits are greatest when it is used along with other interventions, such as education and counseling, that can be delivered via phone or telehealth visits by nurses and care coordinators.

There are “sufficient data” to indicate that adding SMBP monitoring to office-based monitoring is cost-effective compared with office BP monitoring alone or usual care in patients with high office BP, the writing group said.

Potential cost savings associated with SMBP monitoring include a reduction in office visit follow-ups as a result of improved BP control, avoidance of possible overtreatment in patients with white-coat hypertension, and improvement in quality of life.

They noted that randomized controlled trials assessing the impact of SMBP monitoring on cardiovascular outcomes are needed.

Barriers to widespread use

The use of SMBP monitoring is “essential” for the self-management of hypertension and has “great appeal” for expanding the benefits of cardiovascular prevention, the writing group said. They acknowledged, however, that transitioning from solely office-based BP management to a strategy that includes SMBP monitoring is not without actual and potential barriers.

The group recommends addressing these barriers by:

• Educating patients and providers about the benefits of SMBP monitoring and the optimal approaches for SMBP monitoring.
• Establishing clinical core competency criteria to ensure high-quality SMBP monitoring is supported in clinical practice.
• Incorporating cointerventions that increase the effectiveness of SMBP monitoring, including behavioral change management and counseling, communication of treatment recommendations back to patients, medication management, and prescription and adherence monitoring.
• Creating systems for SMBP readings to be transferred from devices to electronic health records.
• Improving public and private health insurance coverage of validated SMBP monitoring devices prescribed by a health care provider.
• Reimbursing providers for costs associated with training patients, transmitting BP data, interpreting and reporting BP readings, and delivering cointerventions.

Increasing the use of SMBP monitoring is a major focus area of Target: BP – a national initiative of the AHA and AMA launched in response to the high prevalence of uncontrolled BP.

Target: BP helps health care organizations and care teams improve BP control rates through the evidence-based MAP BP Program.

MAP is an acronym that stands for Measure BP accurately every time it’s measured, Act rapidly to manage uncontrolled BP, and Partner with patients to promote BP self-management.

This research had no commercial funding. Dr. Shimbo has disclosed no relevant conflicts of interest. A complete list of disclosures for the writing group is available with the original article.
 

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

Self-measured blood pressure (SMBP) monitoring at home is a validated approach to measure out-of-office BP that has the potential to improve the detection and control of hypertension, according to a joint policy statement from the American Heart Association (AHA) and American Medical Association (AMA).

“With fewer patients visiting medical offices during the COVID-19 pandemic, SMBP monitoring is more important than ever for people at risk for hypertension and uncontrolled BP,” writing group chair Daichi Shimbo, MD, said in a statement.

“There should be investment in creating and supporting the infrastructure for expanding self-measured BP monitoring, as well as increasing coverage for patient- and provider-related costs,” Dr. Shimbo, director, The Columbia Hypertension Center, Columbia University Irving Medical Center, New York, said in an interview.

The statement, Self-Measured Blood Pressure Monitoring at Home, was published June 22 in Circulation.

It provides “contemporary information” on the use, efficacy, and cost-effectiveness of SMBP at home for the diagnosis and management of hypertension.

The writing group noted that hypertension is one of the most important risk factors for cardiovascular disease. Several American and international guidelines support the use of SMBP.

“Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension,” the group pointed out.

Use validated devices

Devices that are validated for clinical accuracy should be used for SMBP monitoring, the writing group advised. Validated devices that use the oscillometric method are preferred, and a standardized BP measurement (with appropriately sized cuffs) and monitoring protocol should be followed.

The group noted that meta-analyses of randomized trials indicate that SMBP monitoring is associated with a reduction in BP and improved BP control, and the benefits are greatest when it is used along with other interventions, such as education and counseling, that can be delivered via phone or telehealth visits by nurses and care coordinators.

There are “sufficient data” to indicate that adding SMBP monitoring to office-based monitoring is cost-effective compared with office BP monitoring alone or usual care in patients with high office BP, the writing group said.

Potential cost savings associated with SMBP monitoring include a reduction in office visit follow-ups as a result of improved BP control, avoidance of possible overtreatment in patients with white-coat hypertension, and improvement in quality of life.

They noted that randomized controlled trials assessing the impact of SMBP monitoring on cardiovascular outcomes are needed.

Barriers to widespread use

The use of SMBP monitoring is “essential” for the self-management of hypertension and has “great appeal” for expanding the benefits of cardiovascular prevention, the writing group said. They acknowledged, however, that transitioning from solely office-based BP management to a strategy that includes SMBP monitoring is not without actual and potential barriers.

The group recommends addressing these barriers by:

• Educating patients and providers about the benefits of SMBP monitoring and the optimal approaches for SMBP monitoring.
• Establishing clinical core competency criteria to ensure high-quality SMBP monitoring is supported in clinical practice.
• Incorporating cointerventions that increase the effectiveness of SMBP monitoring, including behavioral change management and counseling, communication of treatment recommendations back to patients, medication management, and prescription and adherence monitoring.
• Creating systems for SMBP readings to be transferred from devices to electronic health records.
• Improving public and private health insurance coverage of validated SMBP monitoring devices prescribed by a health care provider.
• Reimbursing providers for costs associated with training patients, transmitting BP data, interpreting and reporting BP readings, and delivering cointerventions.

Increasing the use of SMBP monitoring is a major focus area of Target: BP – a national initiative of the AHA and AMA launched in response to the high prevalence of uncontrolled BP.

Target: BP helps health care organizations and care teams improve BP control rates through the evidence-based MAP BP Program.

MAP is an acronym that stands for Measure BP accurately every time it’s measured, Act rapidly to manage uncontrolled BP, and Partner with patients to promote BP self-management.

This research had no commercial funding. Dr. Shimbo has disclosed no relevant conflicts of interest. A complete list of disclosures for the writing group is available with the original article.
 

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

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

bjancin@mdedge.com

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

bjancin@mdedge.com

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

bjancin@mdedge.com