Cardiology

As the rigor of COVID-19 research comes under increasing scrutiny, a deep dive into contemporary trials of invasive cardiovascular interventions finds intricate ties with industry and the art of spin on full display.

After examining 216 randomized, controlled trials published in the past decade, researchers found that more than half (53.2%) were commercially funded. In 18.3% of these trials, the sponsor was involved with the trial conduct and reporting.

Commercially sponsored trials were significantly more likely to report results that favored the experimental therapy than trials without commercial sponsorship (64.3% vs. 48.5%; P = .02).

The association remained statistically significant after adjustment for differences in trial characteristics (exponent of regression coefficient beta, 2.80; 95% confidence interval, 1.09-7.18; P = .03), the authors reported in JAMA Internal Medicine.

“To make this clear, this is not an attack on industry-sponsored trials,” study author and cardiac surgeon Mario Gaudino, MD, of New York–Presbyterian and Weill Cornell Medical Center, New York, said in an interview. “Because industry has more money, they have the best trialists, the best research organization. So they generally do a pretty good trial; they’re larger, they have a higher Fragility Index, which means they’re more solid.

“And, most importantly, more than half of the trials were sponsored by industry,” he said. “So without industry, there wouldn’t be half the research in that 10-year period we explored.”

Previous research in cardiology and in other fields has shown that trials supported by for-profit organizations are more likely to report positive findings. The explanations often focus on bias and differential quality in how the trials were designed and reported.

In the present analysis, however, the authors found no difference between trials with and without industry funding in terms of estimated treatment effect, length of follow-up, use of composite or clinically significant outcomes, or outcome modification, compared with the published protocol.

Part of the explanation may be that industry-sponsored trials more often used a noninferiority design (26.1% vs. 14.9%) and had a higher loss of patients to follow-up (median of sample, 1.0% vs. 0.1%), Dr. Gaudino said. “But I think more, in general, it’s not so much a difference in the measurable characteristics of the trial. It’s the selection of the sites that participate, the patient population that is targeted that makes the trial very likely to get the result that industry would like to see.”

“Just think of the differences in the transcatheter MitraClip results between MITRA-FR and COAPT – basically they were related to the fact they enrolled different patients,” he said.
 

Significant spin

The analysis included 216 coronary, vascular, and structural interventional cardiology and vascular and cardiac surgical randomized, controlled trials published from January 2008 to May 31, 2019. Most were multicenter trials (78.7%); 58% originated from Europe, 12% from North America, and 10.6% from Asia.

One in six trials (16.2%) were not prospectively registered before the start of enrollment, and at least one major discrepancy existed between the registered and published primary outcome in 38% of registered trials.

“If you don’t register the trial then you can make all the changes you want to the protocol up until the moment you publish,” Dr. Gaudino observed. “There really is no rational justification for not registering a trial.”

Overall, the trials were not particularly robust, he noted. In 62 trials in which the Fragility Index was measured, only a median of five patients experiencing a different outcome in a commercially sponsored trial would change statistically significant results to nonsignificant. For noncommercially sponsored trials, that number was 4.5 and in four trials; the change in condition of only one patient was needed to switch the statistical significance.

“This finding is concerning given the substantial role that [randomized, controlled trials] results play in federal device approvals, payer criteria, and clinical consensus guidelines,” the authors wrote.

The authors also looked for interpretation bias in the trials. In the 84 trials with nonsignificant differences in the primary outcomes, 65.5% contained spin, such as focusing on statistically significant secondary outcomes or interpreting nonsignificant primary outcomes as showing treatment equivalence or comparable effectiveness. Spin was present in 80.6% of the trials with commercial sponsorship and in 54.2% without (P = .02) – a finding that remained significant after trial differences were controlled for (beta, 4.64; 95% CI, 1.05-20.54; P = .04).
 

A pivot point

“It’s just another paper showing there are issues with conflicts of interest in industry trials. I’m not particularly surprised,” said David Moher, PhD, MSc, director of the Centre for Journalology, based at the Ottawa Hospital Research Institute.

“It’s sort of high time people from all sides sat down together and tried to resolve how to actually move forward with industry wanting to do trials,” he said. “They are hugely important in drug development. How can these trials be done where the impact of industry and, for that matter, academia is minimized?”

Dr. Gaudino suggested the “ideal situation” would be to have industry put its funding into an existing funding organization, such as the National Institutes of Health or a newly created independent organization – a concept that has been floated before without much forward movement.

“We may be at a pivot point,” Dr. Moher said. “It’s quite clear that COVID has indicated some serious problems with how trials are done, how they’re disseminated, the notion of open science. I think this could be an opportunity. Whether there is so much noise, whether anybody will be able to take any of these initiative forward, I don’t know.”

No matter how trial funding is revised, patients must be brought to the table, he said.

“What frustrates me quite a bit is this almost parental view of all of this – the scientists know best, industry knows best,” Dr. Moher said. “We actually need the most important groups: patients and the public. They need to have an enormous amount of say in how this actually is formed.”

Commenting further, Dr. Moher said that “industry and academia can only do trials when they have patients willing to participate, and yet in the discussions you and I are having, what do patients think about spin in trials? I would imagine they would be horrified that they are going into studies – in a sense in many cases risking their lives – and yet people are spinning the results.”

Dr. Gaudino and Dr. Moher reported having no relevant conflicts of interest.

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

As the rigor of COVID-19 research comes under increasing scrutiny, a deep dive into contemporary trials of invasive cardiovascular interventions finds intricate ties with industry and the art of spin on full display.

After examining 216 randomized, controlled trials published in the past decade, researchers found that more than half (53.2%) were commercially funded. In 18.3% of these trials, the sponsor was involved with the trial conduct and reporting.

Commercially sponsored trials were significantly more likely to report results that favored the experimental therapy than trials without commercial sponsorship (64.3% vs. 48.5%; P = .02).

The association remained statistically significant after adjustment for differences in trial characteristics (exponent of regression coefficient beta, 2.80; 95% confidence interval, 1.09-7.18; P = .03), the authors reported in JAMA Internal Medicine.

“To make this clear, this is not an attack on industry-sponsored trials,” study author and cardiac surgeon Mario Gaudino, MD, of New York–Presbyterian and Weill Cornell Medical Center, New York, said in an interview. “Because industry has more money, they have the best trialists, the best research organization. So they generally do a pretty good trial; they’re larger, they have a higher Fragility Index, which means they’re more solid.

“And, most importantly, more than half of the trials were sponsored by industry,” he said. “So without industry, there wouldn’t be half the research in that 10-year period we explored.”

Previous research in cardiology and in other fields has shown that trials supported by for-profit organizations are more likely to report positive findings. The explanations often focus on bias and differential quality in how the trials were designed and reported.

In the present analysis, however, the authors found no difference between trials with and without industry funding in terms of estimated treatment effect, length of follow-up, use of composite or clinically significant outcomes, or outcome modification, compared with the published protocol.

Part of the explanation may be that industry-sponsored trials more often used a noninferiority design (26.1% vs. 14.9%) and had a higher loss of patients to follow-up (median of sample, 1.0% vs. 0.1%), Dr. Gaudino said. “But I think more, in general, it’s not so much a difference in the measurable characteristics of the trial. It’s the selection of the sites that participate, the patient population that is targeted that makes the trial very likely to get the result that industry would like to see.”

“Just think of the differences in the transcatheter MitraClip results between MITRA-FR and COAPT – basically they were related to the fact they enrolled different patients,” he said.
 

Significant spin

The analysis included 216 coronary, vascular, and structural interventional cardiology and vascular and cardiac surgical randomized, controlled trials published from January 2008 to May 31, 2019. Most were multicenter trials (78.7%); 58% originated from Europe, 12% from North America, and 10.6% from Asia.

One in six trials (16.2%) were not prospectively registered before the start of enrollment, and at least one major discrepancy existed between the registered and published primary outcome in 38% of registered trials.

“If you don’t register the trial then you can make all the changes you want to the protocol up until the moment you publish,” Dr. Gaudino observed. “There really is no rational justification for not registering a trial.”

Overall, the trials were not particularly robust, he noted. In 62 trials in which the Fragility Index was measured, only a median of five patients experiencing a different outcome in a commercially sponsored trial would change statistically significant results to nonsignificant. For noncommercially sponsored trials, that number was 4.5 and in four trials; the change in condition of only one patient was needed to switch the statistical significance.

“This finding is concerning given the substantial role that [randomized, controlled trials] results play in federal device approvals, payer criteria, and clinical consensus guidelines,” the authors wrote.

The authors also looked for interpretation bias in the trials. In the 84 trials with nonsignificant differences in the primary outcomes, 65.5% contained spin, such as focusing on statistically significant secondary outcomes or interpreting nonsignificant primary outcomes as showing treatment equivalence or comparable effectiveness. Spin was present in 80.6% of the trials with commercial sponsorship and in 54.2% without (P = .02) – a finding that remained significant after trial differences were controlled for (beta, 4.64; 95% CI, 1.05-20.54; P = .04).
 

A pivot point

“It’s just another paper showing there are issues with conflicts of interest in industry trials. I’m not particularly surprised,” said David Moher, PhD, MSc, director of the Centre for Journalology, based at the Ottawa Hospital Research Institute.

“It’s sort of high time people from all sides sat down together and tried to resolve how to actually move forward with industry wanting to do trials,” he said. “They are hugely important in drug development. How can these trials be done where the impact of industry and, for that matter, academia is minimized?”

Dr. Gaudino suggested the “ideal situation” would be to have industry put its funding into an existing funding organization, such as the National Institutes of Health or a newly created independent organization – a concept that has been floated before without much forward movement.

“We may be at a pivot point,” Dr. Moher said. “It’s quite clear that COVID has indicated some serious problems with how trials are done, how they’re disseminated, the notion of open science. I think this could be an opportunity. Whether there is so much noise, whether anybody will be able to take any of these initiative forward, I don’t know.”

No matter how trial funding is revised, patients must be brought to the table, he said.

“What frustrates me quite a bit is this almost parental view of all of this – the scientists know best, industry knows best,” Dr. Moher said. “We actually need the most important groups: patients and the public. They need to have an enormous amount of say in how this actually is formed.”

Commenting further, Dr. Moher said that “industry and academia can only do trials when they have patients willing to participate, and yet in the discussions you and I are having, what do patients think about spin in trials? I would imagine they would be horrified that they are going into studies – in a sense in many cases risking their lives – and yet people are spinning the results.”

Dr. Gaudino and Dr. Moher reported having no relevant conflicts of interest.

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

As the rigor of COVID-19 research comes under increasing scrutiny, a deep dive into contemporary trials of invasive cardiovascular interventions finds intricate ties with industry and the art of spin on full display.

After examining 216 randomized, controlled trials published in the past decade, researchers found that more than half (53.2%) were commercially funded. In 18.3% of these trials, the sponsor was involved with the trial conduct and reporting.

Commercially sponsored trials were significantly more likely to report results that favored the experimental therapy than trials without commercial sponsorship (64.3% vs. 48.5%; P = .02).

The association remained statistically significant after adjustment for differences in trial characteristics (exponent of regression coefficient beta, 2.80; 95% confidence interval, 1.09-7.18; P = .03), the authors reported in JAMA Internal Medicine.

“To make this clear, this is not an attack on industry-sponsored trials,” study author and cardiac surgeon Mario Gaudino, MD, of New York–Presbyterian and Weill Cornell Medical Center, New York, said in an interview. “Because industry has more money, they have the best trialists, the best research organization. So they generally do a pretty good trial; they’re larger, they have a higher Fragility Index, which means they’re more solid.

“And, most importantly, more than half of the trials were sponsored by industry,” he said. “So without industry, there wouldn’t be half the research in that 10-year period we explored.”

Previous research in cardiology and in other fields has shown that trials supported by for-profit organizations are more likely to report positive findings. The explanations often focus on bias and differential quality in how the trials were designed and reported.

In the present analysis, however, the authors found no difference between trials with and without industry funding in terms of estimated treatment effect, length of follow-up, use of composite or clinically significant outcomes, or outcome modification, compared with the published protocol.

Part of the explanation may be that industry-sponsored trials more often used a noninferiority design (26.1% vs. 14.9%) and had a higher loss of patients to follow-up (median of sample, 1.0% vs. 0.1%), Dr. Gaudino said. “But I think more, in general, it’s not so much a difference in the measurable characteristics of the trial. It’s the selection of the sites that participate, the patient population that is targeted that makes the trial very likely to get the result that industry would like to see.”

“Just think of the differences in the transcatheter MitraClip results between MITRA-FR and COAPT – basically they were related to the fact they enrolled different patients,” he said.
 

Significant spin

The analysis included 216 coronary, vascular, and structural interventional cardiology and vascular and cardiac surgical randomized, controlled trials published from January 2008 to May 31, 2019. Most were multicenter trials (78.7%); 58% originated from Europe, 12% from North America, and 10.6% from Asia.

One in six trials (16.2%) were not prospectively registered before the start of enrollment, and at least one major discrepancy existed between the registered and published primary outcome in 38% of registered trials.

“If you don’t register the trial then you can make all the changes you want to the protocol up until the moment you publish,” Dr. Gaudino observed. “There really is no rational justification for not registering a trial.”

Overall, the trials were not particularly robust, he noted. In 62 trials in which the Fragility Index was measured, only a median of five patients experiencing a different outcome in a commercially sponsored trial would change statistically significant results to nonsignificant. For noncommercially sponsored trials, that number was 4.5 and in four trials; the change in condition of only one patient was needed to switch the statistical significance.

“This finding is concerning given the substantial role that [randomized, controlled trials] results play in federal device approvals, payer criteria, and clinical consensus guidelines,” the authors wrote.

The authors also looked for interpretation bias in the trials. In the 84 trials with nonsignificant differences in the primary outcomes, 65.5% contained spin, such as focusing on statistically significant secondary outcomes or interpreting nonsignificant primary outcomes as showing treatment equivalence or comparable effectiveness. Spin was present in 80.6% of the trials with commercial sponsorship and in 54.2% without (P = .02) – a finding that remained significant after trial differences were controlled for (beta, 4.64; 95% CI, 1.05-20.54; P = .04).
 

A pivot point

“It’s just another paper showing there are issues with conflicts of interest in industry trials. I’m not particularly surprised,” said David Moher, PhD, MSc, director of the Centre for Journalology, based at the Ottawa Hospital Research Institute.

“It’s sort of high time people from all sides sat down together and tried to resolve how to actually move forward with industry wanting to do trials,” he said. “They are hugely important in drug development. How can these trials be done where the impact of industry and, for that matter, academia is minimized?”

Dr. Gaudino suggested the “ideal situation” would be to have industry put its funding into an existing funding organization, such as the National Institutes of Health or a newly created independent organization – a concept that has been floated before without much forward movement.

“We may be at a pivot point,” Dr. Moher said. “It’s quite clear that COVID has indicated some serious problems with how trials are done, how they’re disseminated, the notion of open science. I think this could be an opportunity. Whether there is so much noise, whether anybody will be able to take any of these initiative forward, I don’t know.”

No matter how trial funding is revised, patients must be brought to the table, he said.

“What frustrates me quite a bit is this almost parental view of all of this – the scientists know best, industry knows best,” Dr. Moher said. “We actually need the most important groups: patients and the public. They need to have an enormous amount of say in how this actually is formed.”

Commenting further, Dr. Moher said that “industry and academia can only do trials when they have patients willing to participate, and yet in the discussions you and I are having, what do patients think about spin in trials? I would imagine they would be horrified that they are going into studies – in a sense in many cases risking their lives – and yet people are spinning the results.”

Dr. Gaudino and Dr. Moher reported having no relevant conflicts of interest.

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

The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.

The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.

Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.

The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.

Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.

The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”

The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”

Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.

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






 

The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.

The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.

Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.

The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.

Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.

The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”

The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”

Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.

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






 

The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.

The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.

Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.

The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.

Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.

The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”

The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”

Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.

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






 

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

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

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

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

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

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

The Food and Drug Administration has approved ticagrelor (Brilinta/Brilique, AstraZeneca) for use with aspirin to cut the risk for a first myocardial infarction or stroke in high-risk patients with coronary artery disease (CAD) but no history of MI or stroke, AstraZeneca announced today. 

Patients falling under the new indication do not need to have diabetes, although THEMIS had entered patients with diabetes and CAD, the latter defined as a 50% or greater narrowing of a coronary artery or a history of coronary revascularization but without a history of MI or stroke. 

The trial showed a significant reduction in the rate of the primary efficacy end point (P = .04), a composite of cardiovascular death, MI, and stroke. But the risk of TIMI (Thrombolysis in Myocardial Infarction) bleeding classification major bleeding was more than doubled in the ticagrelor group (P < .001) and the risk for intracranial hemorrhage went up 71% (P = .005). Net clinical benefit didn't differ significantly between the groups in an exploratory analysis. 

The benefit of dual-antiplatelet therapy with ticagrelor for the primary efficacy end point was even more pronounced in a prespecified THEMIS subanalysis of more than 11,000 patients with a history of percutaneous coronary intervention. In this group, the risk for  intracerebral hemorrhage didn't differ significantly between the groups, and the net clinical benefit favored ticagrelor by a significant 15%. 

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

The Food and Drug Administration has approved ticagrelor (Brilinta/Brilique, AstraZeneca) for use with aspirin to cut the risk for a first myocardial infarction or stroke in high-risk patients with coronary artery disease (CAD) but no history of MI or stroke, AstraZeneca announced today. 

Patients falling under the new indication do not need to have diabetes, although THEMIS had entered patients with diabetes and CAD, the latter defined as a 50% or greater narrowing of a coronary artery or a history of coronary revascularization but without a history of MI or stroke. 

The trial showed a significant reduction in the rate of the primary efficacy end point (P = .04), a composite of cardiovascular death, MI, and stroke. But the risk of TIMI (Thrombolysis in Myocardial Infarction) bleeding classification major bleeding was more than doubled in the ticagrelor group (P < .001) and the risk for intracranial hemorrhage went up 71% (P = .005). Net clinical benefit didn't differ significantly between the groups in an exploratory analysis. 

The benefit of dual-antiplatelet therapy with ticagrelor for the primary efficacy end point was even more pronounced in a prespecified THEMIS subanalysis of more than 11,000 patients with a history of percutaneous coronary intervention. In this group, the risk for  intracerebral hemorrhage didn't differ significantly between the groups, and the net clinical benefit favored ticagrelor by a significant 15%. 

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

The Food and Drug Administration has approved ticagrelor (Brilinta/Brilique, AstraZeneca) for use with aspirin to cut the risk for a first myocardial infarction or stroke in high-risk patients with coronary artery disease (CAD) but no history of MI or stroke, AstraZeneca announced today. 

Patients falling under the new indication do not need to have diabetes, although THEMIS had entered patients with diabetes and CAD, the latter defined as a 50% or greater narrowing of a coronary artery or a history of coronary revascularization but without a history of MI or stroke. 

The trial showed a significant reduction in the rate of the primary efficacy end point (P = .04), a composite of cardiovascular death, MI, and stroke. But the risk of TIMI (Thrombolysis in Myocardial Infarction) bleeding classification major bleeding was more than doubled in the ticagrelor group (P < .001) and the risk for intracranial hemorrhage went up 71% (P = .005). Net clinical benefit didn't differ significantly between the groups in an exploratory analysis. 

The benefit of dual-antiplatelet therapy with ticagrelor for the primary efficacy end point was even more pronounced in a prespecified THEMIS subanalysis of more than 11,000 patients with a history of percutaneous coronary intervention. In this group, the risk for  intracerebral hemorrhage didn't differ significantly between the groups, and the net clinical benefit favored ticagrelor by a significant 15%. 

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

Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.

Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.

Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.

The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.

The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.

Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.

The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.

Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.

The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.

“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”

The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”

Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.

They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.

In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).

Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”

Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”

Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.

As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”

His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”

And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”

Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.

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

Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.

Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.

Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.

The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.

The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.

Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.

The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.

Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.

The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.

“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”

The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”

Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.

They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.

In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).

Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”

Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”

Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.

As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”

His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”

And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”

Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.

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

Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.

Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.

Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.

The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.

The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.

Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.

The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.

Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.

The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.

“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”

The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”

Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.

They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.

In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).

Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”

Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”

Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.

As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”

His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”

And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”

Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.

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

The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.

“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.

It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.

“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”

Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.

The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m² who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.

The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.

The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.

Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.

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

The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.

“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.

It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.

“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”

Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.

The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m² who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.

The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.

The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.

Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.

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

The Food and Drug Administration issued an emergency use authorization for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation, Abiomed announced June 1.

“Based on extrapolation of data from the approved indication and reported clinical experience, FDA has concluded that the Impella RP may be effective at providing temporary right ventricular support for the treatment of acute right heart failure or decompensation caused by COVID-19 complications, including PE [pulmonary embolism],” the letter noted.

It cited, for example, use of the temporary heart pump in a 59-year-old woman suffering from COVID-19 who went into right ventricular failure and became hypotensive after an acute PE was removed. After placement of the device, the patient experienced a “dramatic and immediate” improvement in arterial pressure and the device was removed on the fifth day, according to Amir Kaki, MD, and Ted Schreiber, MD, of Ascension St. John Hospital, Detroit, whose review of the case has been posted online.

“Acute pulmonary embolism is clearly being recognized as a life-threatening manifestation of COVID-19. Impella RP is an important tool to help cardiologists save lives during this pandemic,” Dr. Kaki said in the letter. “As we have demonstrated in our series of patients, early recognition of right ventricular dysfunction and early placement of the Impella RP for patients who are hypotensive can be lifesaving.”

Other data cited in support of the Impella RP emergency use authorization (EUA) include a 2019 series of hemodynamically unstable patients with PE in Japan and a 2017 case report of a 47-year-old man with right ventricular failure, profound shock, and a massive PE.

The FDA granted premarket approval of the Impella RP system in 2017 to provide temporary right ventricular support for up to 14 days in patients with a body surface area of at least 1.5 m² who develop acute right heart failure or decompensation following left ventricular assist device implantation, MI, heart transplant, or open-heart surgery.

The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including PE.

The Impella RP is authorized only for emergency use under the EUA and only for the duration of the circumstances justifying use of EUAs, the letter noted.

Last year, concerns were raised about off-indication use after interim results from a postapproval study suggested a higher risk for death than seen in premarket studies treated with the temporary heart pump.

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

A sleep burden index that considers multiple sleep-wake disturbances (SWDs) predicts subsequent cardiocerebrovascular events during the 2 years after a stroke, preliminary results on an ongoing study suggest.

The index, which combines sleep duration, sleep disordered breathing, restless leg syndrome (RLS), insomnia, and sleep duration, is a better predictor of new events than a single sleep disorder alone.

With further evidence of its usefulness, “the sleep burden index could be integrated into clinical routine,” Simone B. Duss, PhD, of the department of neurology at Bern (Switzerland) University Hospital, told a press briefing.

The findings were presented online at the Congress of the European Academy of Neurology 2020, which transitioned to a virtual meeting because of the COVID-19 pandemic.

Sleep-wake disorders are very common in stroke patients and may preexist or appear de novo as a consequence of brain damage, said Dr. Duss. “They may also be a result of medical, psychological, or environmental challenges these patients face after a stroke.”
 

Clear Evidence

There’s “clear evidence” that sleep disordered breathing is a risk factor for stroke, and negatively affects stroke outcome if left untreated, said Dr. Duss.

But for other SWDs, such as insomnia, RLS, and long and short sleep duration, “the evidence is less compelling,” she said. “However, some studies still suggest they influence stroke risk and outcome.”

Experts believe that sleep disturbances after a stroke lead to sleep fragmentation, as well as decreased slow wave sleep and REM sleep.

“This negatively affects inflammatory neuroprotective and synaptic plasticity processes during the recovery process of a stroke,” said Dr. Duss. “In the end, this results in worse outcomes with regard to recurrent events but also in activities of daily living and mood.”

The new analysis aimed to assess the impact of sleep-wake disturbances on recurrent events and outcomes following a stroke or transient ischemic attack (TIA). It included 438 patients with acute stroke (85%) or TIA (15%). The mean age of the study population was 65 years, and 64% were male.

Researchers used the National Institutes of Health Stroke Scale (NIHSS) to assess stroke severity. At admission, the mean NIHSS score was 4. Most strokes (77.2%) were supratentorial.

About one-fifth of stroke patients and one-third of TIA patients had experienced a previous event.

Researchers used functional outcome scores to assess the clinical course of the stroke or TIA. In addition, they regularly asked patients about recurrence of cardiocerebrovascular events.

Investigators assessed sleep disordered breathing during the acute phase of stroke, so within the first few days, using respirography. They collected information on the presence of other sleep-wake disturbances from questionnaires and clinical interviews at 1 month, 3 months, 1 year, and 2 years after the event.

About 26% of subjects showed severe sleep disordered breathing, “meaning that they had more than 20 apnea-hypopnea events per hour,” said Dr. Duss.

More than a quarter of patients reported subclinical symptoms of insomnia (measured using the Insomnia Severity Index), and up to 10% reported severe insomnia symptoms corresponding to the clinical diagnosis of insomnia, she said.

About 9% of patients in the acute phase of stroke, and 6% in the more chronic phase, fulfilled the diagnostic criteria of RLS.
 

More ‘skewed’

The results for sleep duration were relatively “skewed,” said Dr. Duss. More patients reported longer sleep duration (more than 9 hours) at 1 month than at month 3, and more reported shorter sleep duration (4.0 hours or less) at month 3 than at month 1.

The researchers built a sleep burden index for the combined impact of the various sleep-wake disturbances.

They used this index as a predictor of subsequent cardiocerebrovascular events within 3 months after an event. They used a composite outcome that included recurrent stroke or TIA, MI, heart failure, and urgent revascularization, as well as new cardiocerebrovascular events, from 3 to 24 months.

The analysis showed that the mean sleep burden index was higher for stroke patients with a recurrent event, compared with stroke or TIA patients without a recurrent event (P = .0002).

A multiple logistical regression model with the presence or absence of a recurrent event as an outcome showed that the sleep burden index is a significant predictor of recurrent events (odds ratio, 2.10; P = .001). This was true even after controlling for age, gender, and baseline stroke severity.

The baseline apnea/hypopnea index and sleep duration were also significant predictors of new events. Importantly, though, the sleep burden index remained a significant predictor of recurrent events even after excluding the apnea/hypopnea index component, said Dr. Duss. “So the predictive power of the sleep burden index is not only driven by the apnea-hypopnea index at the beginning of a stroke.”

Sleep-wake disturbances “should be more carefully assessed and considered in comprehensive treatment approaches,” not only in stroke patients, but in neurologic patients in general, said Dr. Duss

She noted that these are preliminary observations from an ongoing study. The results need to be confirmed and should be when the study is finalized, she said.

Researchers are also analyzing MRI data to assess whether certain brain lesions are associated with sleep disturbances.

Jesse Dawson, MD, professor of stroke medicine at the University of Glasgow, said the clinical scoring system the study included “will be a big help in design and conduct of clinical trials.”

Although he and other stroke experts are aware of the high prevalence of sleep disorders after stroke, “we don’t routinely look for them as we’re uncertain whether intervention is of benefit,” said Dr. Dawson.

This new study “suggests there is an association with adverse outcome,” he said.

The research was supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. Dr. Duss and Dr. Dawson disclosed no relevant financial relationships.

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

A sleep burden index that considers multiple sleep-wake disturbances (SWDs) predicts subsequent cardiocerebrovascular events during the 2 years after a stroke, preliminary results on an ongoing study suggest.

The index, which combines sleep duration, sleep disordered breathing, restless leg syndrome (RLS), insomnia, and sleep duration, is a better predictor of new events than a single sleep disorder alone.

With further evidence of its usefulness, “the sleep burden index could be integrated into clinical routine,” Simone B. Duss, PhD, of the department of neurology at Bern (Switzerland) University Hospital, told a press briefing.

The findings were presented online at the Congress of the European Academy of Neurology 2020, which transitioned to a virtual meeting because of the COVID-19 pandemic.

Sleep-wake disorders are very common in stroke patients and may preexist or appear de novo as a consequence of brain damage, said Dr. Duss. “They may also be a result of medical, psychological, or environmental challenges these patients face after a stroke.”
 

Clear Evidence

There’s “clear evidence” that sleep disordered breathing is a risk factor for stroke, and negatively affects stroke outcome if left untreated, said Dr. Duss.

But for other SWDs, such as insomnia, RLS, and long and short sleep duration, “the evidence is less compelling,” she said. “However, some studies still suggest they influence stroke risk and outcome.”

Experts believe that sleep disturbances after a stroke lead to sleep fragmentation, as well as decreased slow wave sleep and REM sleep.

“This negatively affects inflammatory neuroprotective and synaptic plasticity processes during the recovery process of a stroke,” said Dr. Duss. “In the end, this results in worse outcomes with regard to recurrent events but also in activities of daily living and mood.”

The new analysis aimed to assess the impact of sleep-wake disturbances on recurrent events and outcomes following a stroke or transient ischemic attack (TIA). It included 438 patients with acute stroke (85%) or TIA (15%). The mean age of the study population was 65 years, and 64% were male.

Researchers used the National Institutes of Health Stroke Scale (NIHSS) to assess stroke severity. At admission, the mean NIHSS score was 4. Most strokes (77.2%) were supratentorial.

About one-fifth of stroke patients and one-third of TIA patients had experienced a previous event.

Researchers used functional outcome scores to assess the clinical course of the stroke or TIA. In addition, they regularly asked patients about recurrence of cardiocerebrovascular events.

Investigators assessed sleep disordered breathing during the acute phase of stroke, so within the first few days, using respirography. They collected information on the presence of other sleep-wake disturbances from questionnaires and clinical interviews at 1 month, 3 months, 1 year, and 2 years after the event.

About 26% of subjects showed severe sleep disordered breathing, “meaning that they had more than 20 apnea-hypopnea events per hour,” said Dr. Duss.

More than a quarter of patients reported subclinical symptoms of insomnia (measured using the Insomnia Severity Index), and up to 10% reported severe insomnia symptoms corresponding to the clinical diagnosis of insomnia, she said.

About 9% of patients in the acute phase of stroke, and 6% in the more chronic phase, fulfilled the diagnostic criteria of RLS.
 

More ‘skewed’

The results for sleep duration were relatively “skewed,” said Dr. Duss. More patients reported longer sleep duration (more than 9 hours) at 1 month than at month 3, and more reported shorter sleep duration (4.0 hours or less) at month 3 than at month 1.

The researchers built a sleep burden index for the combined impact of the various sleep-wake disturbances.

They used this index as a predictor of subsequent cardiocerebrovascular events within 3 months after an event. They used a composite outcome that included recurrent stroke or TIA, MI, heart failure, and urgent revascularization, as well as new cardiocerebrovascular events, from 3 to 24 months.

The analysis showed that the mean sleep burden index was higher for stroke patients with a recurrent event, compared with stroke or TIA patients without a recurrent event (P = .0002).

A multiple logistical regression model with the presence or absence of a recurrent event as an outcome showed that the sleep burden index is a significant predictor of recurrent events (odds ratio, 2.10; P = .001). This was true even after controlling for age, gender, and baseline stroke severity.

The baseline apnea/hypopnea index and sleep duration were also significant predictors of new events. Importantly, though, the sleep burden index remained a significant predictor of recurrent events even after excluding the apnea/hypopnea index component, said Dr. Duss. “So the predictive power of the sleep burden index is not only driven by the apnea-hypopnea index at the beginning of a stroke.”

Sleep-wake disturbances “should be more carefully assessed and considered in comprehensive treatment approaches,” not only in stroke patients, but in neurologic patients in general, said Dr. Duss

She noted that these are preliminary observations from an ongoing study. The results need to be confirmed and should be when the study is finalized, she said.

Researchers are also analyzing MRI data to assess whether certain brain lesions are associated with sleep disturbances.

Jesse Dawson, MD, professor of stroke medicine at the University of Glasgow, said the clinical scoring system the study included “will be a big help in design and conduct of clinical trials.”

Although he and other stroke experts are aware of the high prevalence of sleep disorders after stroke, “we don’t routinely look for them as we’re uncertain whether intervention is of benefit,” said Dr. Dawson.

This new study “suggests there is an association with adverse outcome,” he said.

The research was supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. Dr. Duss and Dr. Dawson disclosed no relevant financial relationships.

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

A sleep burden index that considers multiple sleep-wake disturbances (SWDs) predicts subsequent cardiocerebrovascular events during the 2 years after a stroke, preliminary results on an ongoing study suggest.

The index, which combines sleep duration, sleep disordered breathing, restless leg syndrome (RLS), insomnia, and sleep duration, is a better predictor of new events than a single sleep disorder alone.

With further evidence of its usefulness, “the sleep burden index could be integrated into clinical routine,” Simone B. Duss, PhD, of the department of neurology at Bern (Switzerland) University Hospital, told a press briefing.

The findings were presented online at the Congress of the European Academy of Neurology 2020, which transitioned to a virtual meeting because of the COVID-19 pandemic.

Sleep-wake disorders are very common in stroke patients and may preexist or appear de novo as a consequence of brain damage, said Dr. Duss. “They may also be a result of medical, psychological, or environmental challenges these patients face after a stroke.”
 

Clear Evidence

There’s “clear evidence” that sleep disordered breathing is a risk factor for stroke, and negatively affects stroke outcome if left untreated, said Dr. Duss.

But for other SWDs, such as insomnia, RLS, and long and short sleep duration, “the evidence is less compelling,” she said. “However, some studies still suggest they influence stroke risk and outcome.”

Experts believe that sleep disturbances after a stroke lead to sleep fragmentation, as well as decreased slow wave sleep and REM sleep.

“This negatively affects inflammatory neuroprotective and synaptic plasticity processes during the recovery process of a stroke,” said Dr. Duss. “In the end, this results in worse outcomes with regard to recurrent events but also in activities of daily living and mood.”

The new analysis aimed to assess the impact of sleep-wake disturbances on recurrent events and outcomes following a stroke or transient ischemic attack (TIA). It included 438 patients with acute stroke (85%) or TIA (15%). The mean age of the study population was 65 years, and 64% were male.

Researchers used the National Institutes of Health Stroke Scale (NIHSS) to assess stroke severity. At admission, the mean NIHSS score was 4. Most strokes (77.2%) were supratentorial.

About one-fifth of stroke patients and one-third of TIA patients had experienced a previous event.

Researchers used functional outcome scores to assess the clinical course of the stroke or TIA. In addition, they regularly asked patients about recurrence of cardiocerebrovascular events.

Investigators assessed sleep disordered breathing during the acute phase of stroke, so within the first few days, using respirography. They collected information on the presence of other sleep-wake disturbances from questionnaires and clinical interviews at 1 month, 3 months, 1 year, and 2 years after the event.

About 26% of subjects showed severe sleep disordered breathing, “meaning that they had more than 20 apnea-hypopnea events per hour,” said Dr. Duss.

More than a quarter of patients reported subclinical symptoms of insomnia (measured using the Insomnia Severity Index), and up to 10% reported severe insomnia symptoms corresponding to the clinical diagnosis of insomnia, she said.

About 9% of patients in the acute phase of stroke, and 6% in the more chronic phase, fulfilled the diagnostic criteria of RLS.
 

More ‘skewed’

The results for sleep duration were relatively “skewed,” said Dr. Duss. More patients reported longer sleep duration (more than 9 hours) at 1 month than at month 3, and more reported shorter sleep duration (4.0 hours or less) at month 3 than at month 1.

The researchers built a sleep burden index for the combined impact of the various sleep-wake disturbances.

They used this index as a predictor of subsequent cardiocerebrovascular events within 3 months after an event. They used a composite outcome that included recurrent stroke or TIA, MI, heart failure, and urgent revascularization, as well as new cardiocerebrovascular events, from 3 to 24 months.

The analysis showed that the mean sleep burden index was higher for stroke patients with a recurrent event, compared with stroke or TIA patients without a recurrent event (P = .0002).

A multiple logistical regression model with the presence or absence of a recurrent event as an outcome showed that the sleep burden index is a significant predictor of recurrent events (odds ratio, 2.10; P = .001). This was true even after controlling for age, gender, and baseline stroke severity.

The baseline apnea/hypopnea index and sleep duration were also significant predictors of new events. Importantly, though, the sleep burden index remained a significant predictor of recurrent events even after excluding the apnea/hypopnea index component, said Dr. Duss. “So the predictive power of the sleep burden index is not only driven by the apnea-hypopnea index at the beginning of a stroke.”

Sleep-wake disturbances “should be more carefully assessed and considered in comprehensive treatment approaches,” not only in stroke patients, but in neurologic patients in general, said Dr. Duss

She noted that these are preliminary observations from an ongoing study. The results need to be confirmed and should be when the study is finalized, she said.

Researchers are also analyzing MRI data to assess whether certain brain lesions are associated with sleep disturbances.

Jesse Dawson, MD, professor of stroke medicine at the University of Glasgow, said the clinical scoring system the study included “will be a big help in design and conduct of clinical trials.”

Although he and other stroke experts are aware of the high prevalence of sleep disorders after stroke, “we don’t routinely look for them as we’re uncertain whether intervention is of benefit,” said Dr. Dawson.

This new study “suggests there is an association with adverse outcome,” he said.

The research was supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. Dr. Duss and Dr. Dawson disclosed no relevant financial relationships.

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

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

“Many times, we are looking at results as to whether patients have left main disease or not,” Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “Here, we are showing that it’s not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That’s very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, ‘there is no left main disease.’ But here, we’re seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously.”

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
 

‘Discordance’ revealed in imaging modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. “This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful,” said Dr. Bangalore, who also directs NYU Langone’s Cardiac Catheterization Laboratory. “There may be patients with left main disease, even if the CCTA says it’s not at 25%-29% [stenosis].”

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).
 

Intermediate LMD linked to worse outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362).

“We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD,” Dr. Bangalore said. “Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%].”

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. “This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status.”

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. “But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don’t think that’s any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life.”

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. “I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.,” he said. “If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it’s showing the general burden of atherosclerosis disease in those patients. I think that’s the critical message, that we have to be very aggressive with these patients.”
 

A call for more imaging studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. “With an intermediate lesion, clearly the interventional group did better, and it wasn’t symptom related,” said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. “So even if you do medical therapy, you’re not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding.”

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

dbrunk@mdedge.com

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

“Many times, we are looking at results as to whether patients have left main disease or not,” Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “Here, we are showing that it’s not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That’s very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, ‘there is no left main disease.’ But here, we’re seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously.”

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
 

‘Discordance’ revealed in imaging modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. “This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful,” said Dr. Bangalore, who also directs NYU Langone’s Cardiac Catheterization Laboratory. “There may be patients with left main disease, even if the CCTA says it’s not at 25%-29% [stenosis].”

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).
 

Intermediate LMD linked to worse outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362).

“We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD,” Dr. Bangalore said. “Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%].”

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. “This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status.”

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. “But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don’t think that’s any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life.”

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. “I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.,” he said. “If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it’s showing the general burden of atherosclerosis disease in those patients. I think that’s the critical message, that we have to be very aggressive with these patients.”
 

A call for more imaging studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. “With an intermediate lesion, clearly the interventional group did better, and it wasn’t symptom related,” said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. “So even if you do medical therapy, you’re not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding.”

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

dbrunk@mdedge.com

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

Patients in the landmark ISCHEMIA trial with intermediate left main disease had a greater extent of coronary artery disease on invasive angiography, indicating greater atherosclerotic burden. They also had worse prognosis with a higher risk of cardiovascular events.

“Many times, we are looking at results as to whether patients have left main disease or not,” Sripal Bangalore, MD, said during the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “Here, we are showing that it’s not black and white; there are shades of gray. If a patient has intermediate left main disease, the prognosis is worse. That’s very important information we need to convey to our referrals also, because many times they may just look at the bottom line and say, ‘there is no left main disease.’ But here, we’re seeing that even having intermediate left main disease has significantly worse prognosis. We need to take that seriously.”

Prior studies show that patients with significant left main disease (LMD; defined as 50% or greater stenosis on coronary CT angiography [CCTA]) have a high risk of cardiovascular events and guidelines recommend revascularization to improve survival, said Dr. Bangalore, an interventional cardiologist at New York University Langone Health. However, the impact of intermediate LMD (defined as 25%-49% stenosis on CCTA) on outcomes is unclear.

Members of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) research group randomized 5,179 participants to an initial invasive or conservative strategy. The main results showed that immediate revascularization in patients with stable ischemic heart disease provided no reduction in cardiovascular endpoints through 4 years of follow-up, compared with initial optimal medical therapy alone.
 

‘Discordance’ revealed in imaging modalities

For the current analysis, named the ISCHEMIA Intermediate LM Substudy, those who underwent coronary CCTA comprise the LMD substudy cohort. The objective was to evaluate clinical and quality of life outcomes in patients with and without intermediate left main disease on coronary CT and to evaluate the impact of treatment strategy on those outcomes across subgroups.

At baseline, these patients were categorized into those with and without intermediate LMD as determined by a core lab. Patients with LMD of 50% or greater, those with prior coronary artery bypass graft surgery, and those with nonevaluable or missing data on LM stenosis were excluded.

Among the 3,913 ISCHEMIA participants who underwent CCTA, 3,699 satisfied the inclusion criteria. Of these patients, 962 (26%) had intermediate LMD and 2,737 (74%) did not.

The researchers observed no significant differences in baseline characteristics between patients with and without LMD. However, patients with intermediate LMD tended to be older, and a greater proportion had hypertension and diabetes. Stress test characteristics were also similar between patients with and without LMD. However, patients with intermediate LMD tended toward a greater severity of severe ischemia.

This was also true for anatomic disease on CCTA. A higher proportion of patients with intermediate LMD had triple-vessel disease (61%-62%, compared with 36%-40% along those without intermediate LMD). In addition, a higher proportion of patients with intermediate LMD had stenosis in the proximal left anterior artery descending (LAD) artery (65% vs. 39% among those without intermediate LMD).

On analysis limited to 1,846 patients who underwent invasive angiography treatment in the main ISCHEMIA trial, 7% of those who were categorized into the intermediate LMD group were found to have LMD disease of 50% or greater, compared with 1.4% of patients who were categorized as not having intermediate LMD. “This goes to show this discordance between the two modalities [CCTA and coronary angiography], and I think we have to be careful,” said Dr. Bangalore, who also directs NYU Langone’s Cardiac Catheterization Laboratory. “There may be patients with left main disease, even if the CCTA says it’s not at 25%-29% [stenosis].”

The researchers found that, among patients who underwent invasive angiography, a greater proportion of those who were categorized into the LMD group had proximal LAD disease (43% vs. 33% among those who were categorized into the nonintermediate LMD group), triple-vessel disease (47% vs. 35%), a greater extent of coronary artery disease as denoted by a higher SYNTAX score (21 vs. 15), and a higher proportion underwent coronary artery bypass graft surgery (32% vs. 18%).
 

Intermediate LMD linked to worse outcomes

After the researchers adjusted for baseline differences between the two groups in overall substudy cohort, they found that intermediate LMD severity was an independent predictor of the primary composite endpoint of cardiovascular death, MI, hospitalization for unstable angina, heart failure, and resuscitated cardiac arrest (hazard ratio, 1.31; P = .0123); cardiovascular death/MI/stroke (HR, 1.30; P = .0143); procedural primary MI (HR, 1.64; P = .0487); heart failure (HR, 2.06; P = .0239); and stroke (HR, 1.82, P = .0362).

“We then looked to see if there is a treatment difference, a treatment effect based on whether patients had intermediate LMD,” Dr. Bangalore said. “Most of the P values were not significant. The results are very consistent with what we saw in the main analysis: not a significant difference between invasive and conservative strategy. We do see some differences, though. An invasive strategy was associated with a significantly higher risk of procedural MI [2.9% vs. 1.5%], but a significantly lower risk of nonprocedural MI [–6.4% vs. –2%].”

Dr. Bangalore added that there was significant benefit of the invasive strategy in reducing angina and improving quality of life based on the Seattle Angina Questionnaire-7. “This result was durable up to 48 months of follow-up, whether the patient had intermediate left main disease or not. These results were dependent on baseline angina status. The benefit of invasive strategy was mainly in patients who had daily, weekly, and monthly angina, and no benefit in patients with no angina; there was no interaction based on intermediate left main status.”

Dr. Bangalore emphasized that the original ISCHEMIA trial excluded patients with severe left main disease by design. “But patients with intermediate left main disease in ISCHEMIA tended to have a greater extent of coronary artery disease, indicating greater atherosclerotic burden. I don’t think that’s any surprise. They had a worse prognosis with higher risk of cardiovascular events but similar quality of life, including angina-specific quality of life.”

The key clinical message, he said, is that patients with intermediate LMD face an increased risk of cardiovascular events. “I think we have to be aggressive in trying to reduce their risk with medical therapy, etc.,” he said. “If they are symptomatic, ISCHEMIA tells us that patients have two options. They can choose an invasive strategy, because clearly there is a benefit. You have a significant benefit at making you feel better and potentially reducing the risk of spontaneous MI over a period of time. Or, you can try medical therapy first. If you do see some left main disease, it’s showing the general burden of atherosclerosis disease in those patients. I think that’s the critical message, that we have to be very aggressive with these patients.”
 

A call for more imaging studies

An invited panelist, Timothy D. Henry, MD, said that the results of the ISCHEMIA substudy should stimulate further research. “With an intermediate lesion, clearly the interventional group did better, and it wasn’t symptom related,” said Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research and Education at the Christ Hospital in Cincinnati. “So even if you do medical therapy, you’re not going to really find it out. In my mind, this should stimulate us to do more imaging of the left main that are moderate lesions, and follow this up as an independent study. I think this is a really important finding.”

ISCHEMIA was supported by grants from the National Heart, Lung, and Blood Institute. Dr. Bangalore disclosed that he is a member of the advisory board and/or a board member for Meril, SMT, Pfizer, Amgen, Biotronik, and Abbott. He also is a consultant for Reata Pharmaceuticals.

dbrunk@mdedge.com

SOURCE: Bangalore S et al. SCAI 2020, Abstract 11656.

Background: Often atrial fibrillation terminates spontaneously and occasionally recurs; therefore, the advantage of immediate electric or pharmacologic cardioversion over watchful waiting and subsequent delayed cardioversion is not clear.

This was a noninferiority, open-label study that was not powered enough to study harm between the two strategies. It showed a 30% incidence of recurrence of AFib regardless of study assignment. Hospitalists should not feel pressured to initiate early cardioversion for new-onset AFib. Rate control, anticoagulation (if applicable), prompt follow-up, and early discharge (even from the ED) seem to be a safe and practical approach.

Bottom line: In patients presenting with symptomatic recent-onset AFib, delayed cardioversion in a wait-and-see approach was noninferior to early cardioversion in achieving sinus rhythm at 4 weeks’ follow-up.

Citation: Pluymaekers NA et al. Early or delayed cardioversion in recent-onset atrial fibrillation. N Engl J Med.

2019 Apr 18;380(16):1499-508.

Dr. Abdo is a hospitalist at Duke University Health System.

Background: Often atrial fibrillation terminates spontaneously and occasionally recurs; therefore, the advantage of immediate electric or pharmacologic cardioversion over watchful waiting and subsequent delayed cardioversion is not clear.

This was a noninferiority, open-label study that was not powered enough to study harm between the two strategies. It showed a 30% incidence of recurrence of AFib regardless of study assignment. Hospitalists should not feel pressured to initiate early cardioversion for new-onset AFib. Rate control, anticoagulation (if applicable), prompt follow-up, and early discharge (even from the ED) seem to be a safe and practical approach.

Bottom line: In patients presenting with symptomatic recent-onset AFib, delayed cardioversion in a wait-and-see approach was noninferior to early cardioversion in achieving sinus rhythm at 4 weeks’ follow-up.

Citation: Pluymaekers NA et al. Early or delayed cardioversion in recent-onset atrial fibrillation. N Engl J Med.

2019 Apr 18;380(16):1499-508.

Dr. Abdo is a hospitalist at Duke University Health System.

Background: Often atrial fibrillation terminates spontaneously and occasionally recurs; therefore, the advantage of immediate electric or pharmacologic cardioversion over watchful waiting and subsequent delayed cardioversion is not clear.

This was a noninferiority, open-label study that was not powered enough to study harm between the two strategies. It showed a 30% incidence of recurrence of AFib regardless of study assignment. Hospitalists should not feel pressured to initiate early cardioversion for new-onset AFib. Rate control, anticoagulation (if applicable), prompt follow-up, and early discharge (even from the ED) seem to be a safe and practical approach.

Bottom line: In patients presenting with symptomatic recent-onset AFib, delayed cardioversion in a wait-and-see approach was noninferior to early cardioversion in achieving sinus rhythm at 4 weeks’ follow-up.

Citation: Pluymaekers NA et al. Early or delayed cardioversion in recent-onset atrial fibrillation. N Engl J Med.

2019 Apr 18;380(16):1499-508.

Dr. Abdo is a hospitalist at Duke University Health System.