Emergency Medicine

Treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%, a meta-analysis of four published studies has shown.

RogerAshford/Thinkstock

In the analysis that included almost 9,000 COVID-19 patients, there was a significantly reduced risk for fatal or severe COVID-19 among patients who were users of statins, compared with nonusers (pooled hazard ratio, 0.70; 95% confidence interval, 0.53-0.94).

Based on the findings, “it may be time we shift our focus to statins as the potential therapeutic options in COVID-19 patients,” authors Syed Shahzad Hasan, PhD, University of Huddersfield (England), and Chia Siang Kow, MPharm, International Medical University, Kuala Lumpur, Malaysia, said in an interview.

The study was published online August 11 in The American Journal of Cardiology.
 

Moderate- to good-quality data

The analysis included four studies published up to July 27 of this year. Eligible studies included those with a cohort or case-control designs, enrolled patients with confirmed COVID-19, and had data available allowing comparison of the risk of severe illness and/or mortality among statin users versus nonusers in adjusted analyses, the authors noted.

The four studies – one of “moderate” quality and three of “good” quality – included a total of 8,990 COVID-19 patients.

In the pooled analysis, there was a significantly reduced risk for fatal or severe COVID-19 with use of statins, compared with non-use of statins (pooled HR, 0.70; 95% CI, 0.53-0.94).

Their findings also “discredited the suggestion of harms with the use of statins in COVID-19 patients,” the authors concluded.

“Since our meta-analysis included a fairly large total number of COVID-19 patients from four studies in which three are large-scale studies that adjusted extensively for multiple potential confounding factors, the findings can be considered reliable,” Dr. Hasan and Mr. Kow wrote in their article.

Based on the results, “moderate- to high-intensity statin therapy is likely to be beneficial” in patients with COVID-19, they said.

However, they cautioned that more data from prospective studies are needed to substantiate the findings and to determine the appropriate regimen for a statin in COVID-19 patients.

Yibin Wang, PhD, of the University of California, Los Angeles, said that “this is a very simple meta-analysis from four published studies which consistently reported a protective or neutral effect of statin usage on mortality or severe complications in COVID-19 patients.”

Although the scope of this meta-analysis was “quite limited, the conclusion was not unexpected, as most of the clinical analysis so far reported supports the benefits or safety of statin usage in COVID-19 patients,” Dr. Wang said in an interview.
 

Nonetheless, questions remain

While there is “almost no dispute” about the safety of continuing statin therapy in COVID-19 patients, it remains to be determined if statin therapy can be implemented as an adjuvant or independent therapy and a part of the standard care for COVID-19 patients regardless of their hyperlipidemia status, said Dr. Wang, who was not associated with Dr. Hasan’s and Mr. Kow’s research.

“While statin usage is associated with several beneficial effects such as anti-inflammation and cytoprotection, these effects are usually observed from long-term usage rather than short-term/acute administration. Therefore, prospective studies and randomized trials should be conducted to test the efficacy of stain usage for COVID-19 patients with mild to severe symptoms,” he noted.

“Considering the excellent record of statins as a safe and cheap drug, it is certainly a worthwhile effort to consider its broad-based usage for COVID-19 in order to lower the overall death and severe complications,” Dr. Wang concluded.

Guillermo Rodriguez-Nava, MD, department of internal medicine, AMITA Health Saint Francis Hospital, Evanston, Ill., is first author on one of the studies included in this meta-analysis.

The retrospective, single-center study found slower progression to death associated with atorvastatin in older patients with COVID-19 admitted to the ICU. 

“Currently, there are hundreds of clinical trials evaluating a wide variety of pharmacological therapies for COVID-19. Unfortunately, these trials take time, and we are getting results in dribs and drabs,” Dr. Rodriguez-Nava said in an interview.

“In the meantime, the best available evidence is observational, and COVID-19 treatment regiments will continue to evolve. Whether atorvastatin is effective against COVID-19 is still under investigation. Nevertheless, clinicians should consider at least continuing them in patients with COVID-19,” he advised.

The study had no specific funding. Dr. Hasan, Mr. Kow, Dr. Wang, and Dr. Rodriguez-Nava disclosed no relationships relevant to this research.

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

Treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%, a meta-analysis of four published studies has shown.

RogerAshford/Thinkstock

In the analysis that included almost 9,000 COVID-19 patients, there was a significantly reduced risk for fatal or severe COVID-19 among patients who were users of statins, compared with nonusers (pooled hazard ratio, 0.70; 95% confidence interval, 0.53-0.94).

Based on the findings, “it may be time we shift our focus to statins as the potential therapeutic options in COVID-19 patients,” authors Syed Shahzad Hasan, PhD, University of Huddersfield (England), and Chia Siang Kow, MPharm, International Medical University, Kuala Lumpur, Malaysia, said in an interview.

The study was published online August 11 in The American Journal of Cardiology.
 

Moderate- to good-quality data

The analysis included four studies published up to July 27 of this year. Eligible studies included those with a cohort or case-control designs, enrolled patients with confirmed COVID-19, and had data available allowing comparison of the risk of severe illness and/or mortality among statin users versus nonusers in adjusted analyses, the authors noted.

The four studies – one of “moderate” quality and three of “good” quality – included a total of 8,990 COVID-19 patients.

In the pooled analysis, there was a significantly reduced risk for fatal or severe COVID-19 with use of statins, compared with non-use of statins (pooled HR, 0.70; 95% CI, 0.53-0.94).

Their findings also “discredited the suggestion of harms with the use of statins in COVID-19 patients,” the authors concluded.

“Since our meta-analysis included a fairly large total number of COVID-19 patients from four studies in which three are large-scale studies that adjusted extensively for multiple potential confounding factors, the findings can be considered reliable,” Dr. Hasan and Mr. Kow wrote in their article.

Based on the results, “moderate- to high-intensity statin therapy is likely to be beneficial” in patients with COVID-19, they said.

However, they cautioned that more data from prospective studies are needed to substantiate the findings and to determine the appropriate regimen for a statin in COVID-19 patients.

Yibin Wang, PhD, of the University of California, Los Angeles, said that “this is a very simple meta-analysis from four published studies which consistently reported a protective or neutral effect of statin usage on mortality or severe complications in COVID-19 patients.”

Although the scope of this meta-analysis was “quite limited, the conclusion was not unexpected, as most of the clinical analysis so far reported supports the benefits or safety of statin usage in COVID-19 patients,” Dr. Wang said in an interview.
 

Nonetheless, questions remain

While there is “almost no dispute” about the safety of continuing statin therapy in COVID-19 patients, it remains to be determined if statin therapy can be implemented as an adjuvant or independent therapy and a part of the standard care for COVID-19 patients regardless of their hyperlipidemia status, said Dr. Wang, who was not associated with Dr. Hasan’s and Mr. Kow’s research.

“While statin usage is associated with several beneficial effects such as anti-inflammation and cytoprotection, these effects are usually observed from long-term usage rather than short-term/acute administration. Therefore, prospective studies and randomized trials should be conducted to test the efficacy of stain usage for COVID-19 patients with mild to severe symptoms,” he noted.

“Considering the excellent record of statins as a safe and cheap drug, it is certainly a worthwhile effort to consider its broad-based usage for COVID-19 in order to lower the overall death and severe complications,” Dr. Wang concluded.

Guillermo Rodriguez-Nava, MD, department of internal medicine, AMITA Health Saint Francis Hospital, Evanston, Ill., is first author on one of the studies included in this meta-analysis.

The retrospective, single-center study found slower progression to death associated with atorvastatin in older patients with COVID-19 admitted to the ICU. 

“Currently, there are hundreds of clinical trials evaluating a wide variety of pharmacological therapies for COVID-19. Unfortunately, these trials take time, and we are getting results in dribs and drabs,” Dr. Rodriguez-Nava said in an interview.

“In the meantime, the best available evidence is observational, and COVID-19 treatment regiments will continue to evolve. Whether atorvastatin is effective against COVID-19 is still under investigation. Nevertheless, clinicians should consider at least continuing them in patients with COVID-19,” he advised.

The study had no specific funding. Dr. Hasan, Mr. Kow, Dr. Wang, and Dr. Rodriguez-Nava disclosed no relationships relevant to this research.

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

Treatment with statins was associated with a reduced risk of a severe or fatal course of COVID-19 by 30%, a meta-analysis of four published studies has shown.

RogerAshford/Thinkstock

In the analysis that included almost 9,000 COVID-19 patients, there was a significantly reduced risk for fatal or severe COVID-19 among patients who were users of statins, compared with nonusers (pooled hazard ratio, 0.70; 95% confidence interval, 0.53-0.94).

Based on the findings, “it may be time we shift our focus to statins as the potential therapeutic options in COVID-19 patients,” authors Syed Shahzad Hasan, PhD, University of Huddersfield (England), and Chia Siang Kow, MPharm, International Medical University, Kuala Lumpur, Malaysia, said in an interview.

The study was published online August 11 in The American Journal of Cardiology.
 

Moderate- to good-quality data

The analysis included four studies published up to July 27 of this year. Eligible studies included those with a cohort or case-control designs, enrolled patients with confirmed COVID-19, and had data available allowing comparison of the risk of severe illness and/or mortality among statin users versus nonusers in adjusted analyses, the authors noted.

The four studies – one of “moderate” quality and three of “good” quality – included a total of 8,990 COVID-19 patients.

In the pooled analysis, there was a significantly reduced risk for fatal or severe COVID-19 with use of statins, compared with non-use of statins (pooled HR, 0.70; 95% CI, 0.53-0.94).

Their findings also “discredited the suggestion of harms with the use of statins in COVID-19 patients,” the authors concluded.

“Since our meta-analysis included a fairly large total number of COVID-19 patients from four studies in which three are large-scale studies that adjusted extensively for multiple potential confounding factors, the findings can be considered reliable,” Dr. Hasan and Mr. Kow wrote in their article.

Based on the results, “moderate- to high-intensity statin therapy is likely to be beneficial” in patients with COVID-19, they said.

However, they cautioned that more data from prospective studies are needed to substantiate the findings and to determine the appropriate regimen for a statin in COVID-19 patients.

Yibin Wang, PhD, of the University of California, Los Angeles, said that “this is a very simple meta-analysis from four published studies which consistently reported a protective or neutral effect of statin usage on mortality or severe complications in COVID-19 patients.”

Although the scope of this meta-analysis was “quite limited, the conclusion was not unexpected, as most of the clinical analysis so far reported supports the benefits or safety of statin usage in COVID-19 patients,” Dr. Wang said in an interview.
 

Nonetheless, questions remain

While there is “almost no dispute” about the safety of continuing statin therapy in COVID-19 patients, it remains to be determined if statin therapy can be implemented as an adjuvant or independent therapy and a part of the standard care for COVID-19 patients regardless of their hyperlipidemia status, said Dr. Wang, who was not associated with Dr. Hasan’s and Mr. Kow’s research.

“While statin usage is associated with several beneficial effects such as anti-inflammation and cytoprotection, these effects are usually observed from long-term usage rather than short-term/acute administration. Therefore, prospective studies and randomized trials should be conducted to test the efficacy of stain usage for COVID-19 patients with mild to severe symptoms,” he noted.

“Considering the excellent record of statins as a safe and cheap drug, it is certainly a worthwhile effort to consider its broad-based usage for COVID-19 in order to lower the overall death and severe complications,” Dr. Wang concluded.

Guillermo Rodriguez-Nava, MD, department of internal medicine, AMITA Health Saint Francis Hospital, Evanston, Ill., is first author on one of the studies included in this meta-analysis.

The retrospective, single-center study found slower progression to death associated with atorvastatin in older patients with COVID-19 admitted to the ICU. 

“Currently, there are hundreds of clinical trials evaluating a wide variety of pharmacological therapies for COVID-19. Unfortunately, these trials take time, and we are getting results in dribs and drabs,” Dr. Rodriguez-Nava said in an interview.

“In the meantime, the best available evidence is observational, and COVID-19 treatment regiments will continue to evolve. Whether atorvastatin is effective against COVID-19 is still under investigation. Nevertheless, clinicians should consider at least continuing them in patients with COVID-19,” he advised.

The study had no specific funding. Dr. Hasan, Mr. Kow, Dr. Wang, and Dr. Rodriguez-Nava disclosed no relationships relevant to this research.

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

A restrictive blood transfusion strategy in myocardial infarction patients with anemia proved safe, significantly less costly, and at least as effective as the standard liberal transfusion strategy in the landmark REALITY trial.

Randomized trial data already support a restrictive transfusion strategy in patients undergoing cardiac and noncardiac surgery, as well as in other settings. Those trials deliberately excluded patients with acute myocardial ischemia.

Cardiologists have been loath to adopt a restrictive strategy in the absence of persuasive supporting evidence because of a theoretic concern that low hemoglobin might be particularly harmful to ischemic myocardium. Anemia occurs in 5%-10% patients with MI, and clinicians have been eager for evidence-based guidance on how to best manage it.

“Blood is a precious resource and transfusion is costly, logistically cumbersome, and has side effects,” Philippe Gabriel Steg, MD, chair of the REALITY trial, noted in presenting the study results at the virtual annual congress of the European Society of Cardiology.

REALITY was the first-ever large randomized trial of a restrictive versus liberal transfusion strategy in acute MI. The study, which featured a noninferiority design, included 668 stable patients with acute MI and anemia with a hemoglobin of 7-10 g/dL at 35 hospitals in France and Spain. Participants were randomized to a restrictive strategy in which transfusion was withheld unless the hemoglobin dropped to 8 g/dL or less, or to a conventional liberal strategy triggered by a hemoglobin of 10 g/dL or lower. The transfusion target was a hemoglobin level of 8-10 g/dL in the restrictive strategy group and greater than 11 g/dL in the liberal transfusion group. In the restrictive transfusion group, 36% received at least one RBC transfusion, as did 87% in the liberal transfusion study arm. The restrictive strategy group used 414 fewer units of blood.

The two coprimary endpoints were 30-day major adverse cardiovascular events and cost-effectiveness. The 30-day composite of all-cause mortality, reinfarction, stroke, and emergency percutaneous coronary intervention for myocardial ischemia occurred in 11% of the restrictive transfusion group and 14% of the liberal transfusion group. The resultant 21% relative risk reduction established that the restrictive strategy was noninferior. Of note, all of the individual components of the composite endpoint numerically favored the restrictive approach.

In terms of safety, patients in the restrictive transfusion group were significantly less likely to develop an infection, by a margin of 0% versus 1.5%. The rate of acute lung injury was also significantly lower in the restrictive group: 0.3%, compared with 2.2%. The median hospital length of stay was identical at 7 days in both groups.

The cost-effectiveness analysis concluded that the restrictive transfusion strategy had an 84% probability of being both less expensive and more effective.

Patients were enrolled in REALITY regardless of whether they had active bleeding, as long as the bleeding wasn’t deemed massive and life-threatening. Notably, there was no difference in the results of restrictive versus liberal transfusion regardless of whether active bleeding was present, nor did baseline hemoglobin or the presence or absence of preexisting anemia affect the results.

Dr. Steg noted that a much larger randomized trial of restrictive versus liberal transfusion in the setting of acute MI with anemia is underway in the United States and Canada. The 3,000-patient MINT trial, sponsored by the National Institutes of Health, is testing the superiority of restrictive transfusion, rather than its noninferiority, as in REALITY. Results are a couple of years away.

“I think that will be an important piece of additional evidence,” he said.

Discussant Marco Roffi, MD, didn’t mince words.

“I really love the REALITY trial,” declared Dr. Roffi, professor and vice chairman of the cardiology department and director of the interventional cardiology unit at University Hospital of Geneva.

He ticked off a series of reasons: The trial addressed a common clinical dilemma about which there has been essentially no prior high-quality evidence, it provided convincing results, and it carried important implications for responsible stewardship of the blood supply.

“REALITY allows clinicians to comfortably refrain from transfusing anemic patients presenting with myocardial infarction, and this should lead to a reduction in the consumption of blood products,” Dr. Roffi said.

He applauded the investigators for their success in obtaining public funding for a study lacking a commercial hook. And as a clinical investigator, he was particularly impressed by one of the technical details about the REALITY trial: “I was amazed by the fact that the observed event rates virtually corresponded to the estimated ones used for the power calculations. This is rarely the case in such a trial.”

Dr. Roffi said the REALITY findings should have an immediate impact on clinical practice, as well as on the brand new 2020 ESC guidelines on the management of non–ST-elevation ACS issued during the ESC virtual congress.

The freshly inked guidelines state: “Based on inconsistent study results and the lack of adequately powered randomized, controlled trials, a restrictive policy of transfusion in anemic patients with MI may be considered.” As of today, Dr. Roffi argued, the phrase “may be considered” ought to be replaced by the stronger phrase “should be considered.”

During the discussion period, he was asked if it’s appropriate to extrapolate the REALITY results to patients undergoing transcatheter aortic valve replacement, among whom anemia is highly prevalent.

“I think this is a different patient population. Nevertheless, the concept of being restrictive is one that in my opinion now remains until proven otherwise. So we are being very restrictive in these patients,” he replied.

Asked about possible mechanisms by which liberal transfusion might have detrimental effects in acute MI patients, Dr. Steg cited several, including evidence that transfusion may not improve oxygen delivery to as great an extent as traditionally thought. There is also the risk of volume overload, increased blood viscosity, and enhanced platelet aggregation and activation, which could promote myocardial ischemia.

The REALITY trial was funded by the French Ministry of Health and the Spanish Ministry of Economy and Competitiveness with no commercial support. Outside the scope of the trial, Dr. Steg reported receiving research grants from Bayer, Merck, Servier, and Sanofi as well as serving as a consultant to numerous pharmaceutical companies.

[email protected]

A restrictive blood transfusion strategy in myocardial infarction patients with anemia proved safe, significantly less costly, and at least as effective as the standard liberal transfusion strategy in the landmark REALITY trial.

Randomized trial data already support a restrictive transfusion strategy in patients undergoing cardiac and noncardiac surgery, as well as in other settings. Those trials deliberately excluded patients with acute myocardial ischemia.

Cardiologists have been loath to adopt a restrictive strategy in the absence of persuasive supporting evidence because of a theoretic concern that low hemoglobin might be particularly harmful to ischemic myocardium. Anemia occurs in 5%-10% patients with MI, and clinicians have been eager for evidence-based guidance on how to best manage it.

“Blood is a precious resource and transfusion is costly, logistically cumbersome, and has side effects,” Philippe Gabriel Steg, MD, chair of the REALITY trial, noted in presenting the study results at the virtual annual congress of the European Society of Cardiology.

REALITY was the first-ever large randomized trial of a restrictive versus liberal transfusion strategy in acute MI. The study, which featured a noninferiority design, included 668 stable patients with acute MI and anemia with a hemoglobin of 7-10 g/dL at 35 hospitals in France and Spain. Participants were randomized to a restrictive strategy in which transfusion was withheld unless the hemoglobin dropped to 8 g/dL or less, or to a conventional liberal strategy triggered by a hemoglobin of 10 g/dL or lower. The transfusion target was a hemoglobin level of 8-10 g/dL in the restrictive strategy group and greater than 11 g/dL in the liberal transfusion group. In the restrictive transfusion group, 36% received at least one RBC transfusion, as did 87% in the liberal transfusion study arm. The restrictive strategy group used 414 fewer units of blood.

The two coprimary endpoints were 30-day major adverse cardiovascular events and cost-effectiveness. The 30-day composite of all-cause mortality, reinfarction, stroke, and emergency percutaneous coronary intervention for myocardial ischemia occurred in 11% of the restrictive transfusion group and 14% of the liberal transfusion group. The resultant 21% relative risk reduction established that the restrictive strategy was noninferior. Of note, all of the individual components of the composite endpoint numerically favored the restrictive approach.

In terms of safety, patients in the restrictive transfusion group were significantly less likely to develop an infection, by a margin of 0% versus 1.5%. The rate of acute lung injury was also significantly lower in the restrictive group: 0.3%, compared with 2.2%. The median hospital length of stay was identical at 7 days in both groups.

The cost-effectiveness analysis concluded that the restrictive transfusion strategy had an 84% probability of being both less expensive and more effective.

Patients were enrolled in REALITY regardless of whether they had active bleeding, as long as the bleeding wasn’t deemed massive and life-threatening. Notably, there was no difference in the results of restrictive versus liberal transfusion regardless of whether active bleeding was present, nor did baseline hemoglobin or the presence or absence of preexisting anemia affect the results.

Dr. Steg noted that a much larger randomized trial of restrictive versus liberal transfusion in the setting of acute MI with anemia is underway in the United States and Canada. The 3,000-patient MINT trial, sponsored by the National Institutes of Health, is testing the superiority of restrictive transfusion, rather than its noninferiority, as in REALITY. Results are a couple of years away.

“I think that will be an important piece of additional evidence,” he said.

Discussant Marco Roffi, MD, didn’t mince words.

“I really love the REALITY trial,” declared Dr. Roffi, professor and vice chairman of the cardiology department and director of the interventional cardiology unit at University Hospital of Geneva.

He ticked off a series of reasons: The trial addressed a common clinical dilemma about which there has been essentially no prior high-quality evidence, it provided convincing results, and it carried important implications for responsible stewardship of the blood supply.

“REALITY allows clinicians to comfortably refrain from transfusing anemic patients presenting with myocardial infarction, and this should lead to a reduction in the consumption of blood products,” Dr. Roffi said.

He applauded the investigators for their success in obtaining public funding for a study lacking a commercial hook. And as a clinical investigator, he was particularly impressed by one of the technical details about the REALITY trial: “I was amazed by the fact that the observed event rates virtually corresponded to the estimated ones used for the power calculations. This is rarely the case in such a trial.”

Dr. Roffi said the REALITY findings should have an immediate impact on clinical practice, as well as on the brand new 2020 ESC guidelines on the management of non–ST-elevation ACS issued during the ESC virtual congress.

The freshly inked guidelines state: “Based on inconsistent study results and the lack of adequately powered randomized, controlled trials, a restrictive policy of transfusion in anemic patients with MI may be considered.” As of today, Dr. Roffi argued, the phrase “may be considered” ought to be replaced by the stronger phrase “should be considered.”

During the discussion period, he was asked if it’s appropriate to extrapolate the REALITY results to patients undergoing transcatheter aortic valve replacement, among whom anemia is highly prevalent.

“I think this is a different patient population. Nevertheless, the concept of being restrictive is one that in my opinion now remains until proven otherwise. So we are being very restrictive in these patients,” he replied.

Asked about possible mechanisms by which liberal transfusion might have detrimental effects in acute MI patients, Dr. Steg cited several, including evidence that transfusion may not improve oxygen delivery to as great an extent as traditionally thought. There is also the risk of volume overload, increased blood viscosity, and enhanced platelet aggregation and activation, which could promote myocardial ischemia.

The REALITY trial was funded by the French Ministry of Health and the Spanish Ministry of Economy and Competitiveness with no commercial support. Outside the scope of the trial, Dr. Steg reported receiving research grants from Bayer, Merck, Servier, and Sanofi as well as serving as a consultant to numerous pharmaceutical companies.

[email protected]

A restrictive blood transfusion strategy in myocardial infarction patients with anemia proved safe, significantly less costly, and at least as effective as the standard liberal transfusion strategy in the landmark REALITY trial.

Randomized trial data already support a restrictive transfusion strategy in patients undergoing cardiac and noncardiac surgery, as well as in other settings. Those trials deliberately excluded patients with acute myocardial ischemia.

Cardiologists have been loath to adopt a restrictive strategy in the absence of persuasive supporting evidence because of a theoretic concern that low hemoglobin might be particularly harmful to ischemic myocardium. Anemia occurs in 5%-10% patients with MI, and clinicians have been eager for evidence-based guidance on how to best manage it.

“Blood is a precious resource and transfusion is costly, logistically cumbersome, and has side effects,” Philippe Gabriel Steg, MD, chair of the REALITY trial, noted in presenting the study results at the virtual annual congress of the European Society of Cardiology.

REALITY was the first-ever large randomized trial of a restrictive versus liberal transfusion strategy in acute MI. The study, which featured a noninferiority design, included 668 stable patients with acute MI and anemia with a hemoglobin of 7-10 g/dL at 35 hospitals in France and Spain. Participants were randomized to a restrictive strategy in which transfusion was withheld unless the hemoglobin dropped to 8 g/dL or less, or to a conventional liberal strategy triggered by a hemoglobin of 10 g/dL or lower. The transfusion target was a hemoglobin level of 8-10 g/dL in the restrictive strategy group and greater than 11 g/dL in the liberal transfusion group. In the restrictive transfusion group, 36% received at least one RBC transfusion, as did 87% in the liberal transfusion study arm. The restrictive strategy group used 414 fewer units of blood.

The two coprimary endpoints were 30-day major adverse cardiovascular events and cost-effectiveness. The 30-day composite of all-cause mortality, reinfarction, stroke, and emergency percutaneous coronary intervention for myocardial ischemia occurred in 11% of the restrictive transfusion group and 14% of the liberal transfusion group. The resultant 21% relative risk reduction established that the restrictive strategy was noninferior. Of note, all of the individual components of the composite endpoint numerically favored the restrictive approach.

In terms of safety, patients in the restrictive transfusion group were significantly less likely to develop an infection, by a margin of 0% versus 1.5%. The rate of acute lung injury was also significantly lower in the restrictive group: 0.3%, compared with 2.2%. The median hospital length of stay was identical at 7 days in both groups.

The cost-effectiveness analysis concluded that the restrictive transfusion strategy had an 84% probability of being both less expensive and more effective.

Patients were enrolled in REALITY regardless of whether they had active bleeding, as long as the bleeding wasn’t deemed massive and life-threatening. Notably, there was no difference in the results of restrictive versus liberal transfusion regardless of whether active bleeding was present, nor did baseline hemoglobin or the presence or absence of preexisting anemia affect the results.

Dr. Steg noted that a much larger randomized trial of restrictive versus liberal transfusion in the setting of acute MI with anemia is underway in the United States and Canada. The 3,000-patient MINT trial, sponsored by the National Institutes of Health, is testing the superiority of restrictive transfusion, rather than its noninferiority, as in REALITY. Results are a couple of years away.

“I think that will be an important piece of additional evidence,” he said.

Discussant Marco Roffi, MD, didn’t mince words.

“I really love the REALITY trial,” declared Dr. Roffi, professor and vice chairman of the cardiology department and director of the interventional cardiology unit at University Hospital of Geneva.

He ticked off a series of reasons: The trial addressed a common clinical dilemma about which there has been essentially no prior high-quality evidence, it provided convincing results, and it carried important implications for responsible stewardship of the blood supply.

“REALITY allows clinicians to comfortably refrain from transfusing anemic patients presenting with myocardial infarction, and this should lead to a reduction in the consumption of blood products,” Dr. Roffi said.

He applauded the investigators for their success in obtaining public funding for a study lacking a commercial hook. And as a clinical investigator, he was particularly impressed by one of the technical details about the REALITY trial: “I was amazed by the fact that the observed event rates virtually corresponded to the estimated ones used for the power calculations. This is rarely the case in such a trial.”

Dr. Roffi said the REALITY findings should have an immediate impact on clinical practice, as well as on the brand new 2020 ESC guidelines on the management of non–ST-elevation ACS issued during the ESC virtual congress.

The freshly inked guidelines state: “Based on inconsistent study results and the lack of adequately powered randomized, controlled trials, a restrictive policy of transfusion in anemic patients with MI may be considered.” As of today, Dr. Roffi argued, the phrase “may be considered” ought to be replaced by the stronger phrase “should be considered.”

During the discussion period, he was asked if it’s appropriate to extrapolate the REALITY results to patients undergoing transcatheter aortic valve replacement, among whom anemia is highly prevalent.

“I think this is a different patient population. Nevertheless, the concept of being restrictive is one that in my opinion now remains until proven otherwise. So we are being very restrictive in these patients,” he replied.

Asked about possible mechanisms by which liberal transfusion might have detrimental effects in acute MI patients, Dr. Steg cited several, including evidence that transfusion may not improve oxygen delivery to as great an extent as traditionally thought. There is also the risk of volume overload, increased blood viscosity, and enhanced platelet aggregation and activation, which could promote myocardial ischemia.

The REALITY trial was funded by the French Ministry of Health and the Spanish Ministry of Economy and Competitiveness with no commercial support. Outside the scope of the trial, Dr. Steg reported receiving research grants from Bayer, Merck, Servier, and Sanofi as well as serving as a consultant to numerous pharmaceutical companies.

[email protected]

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

The first randomized study to compare continuing versus stopping ACE inhibitors or angiotensin receptor blockers (ARBs) for patients with COVID-19 has shown no difference in key outcomes between the two approaches.

European Society of Cardiology

The BRACE CORONA trial – conducted in patients had been taking an ACE inhibitor or an ARB on a long-term basis and who were subsequently hospitalized with COVID-19 – showed no difference in the primary endpoint of number of days alive and out of hospital among those whose medication was suspended for 30 days and those who continued undergoing treatment with these agents.

“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” principal investigator Renato Lopes, MD, of Duke Clinical Research Institute, Durham, N.C., concluded.

The BRACE CORONA trial was presented at the European Society of Cardiology Congress 2020 on Sept. 1.

Dr. Lopes explained that there are two conflicting hypotheses about the role of ACE inhibitors and ARBs in COVID-19.

One hypothesis suggests that use of these drugs could be harmful by increasing the expression of ACE2 receptors (which the SARS-CoV-2 virus uses to gain entry into cells), thus potentially enhancing viral binding and viral entry. The other suggests that ACE inhibitors and ARBs could be protective by reducing production of angiotensin II and enhancing the generation of angiotensin 1-7, which attenuates inflammation and fibrosis and therefore could attenuate lung injury.

The BRACE CORONA trial was an academic-led randomized study that tested two strategies: temporarily stopping the ACE inhibitor/ARB for 30 days or continuing these drugs for patients who had been taking these medications on a long-term basis and were hospitalized with a confirmed diagnosis of COVID-19.

The primary outcome was the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs or sacubitril/valsartan or who were hemodynamically unstable at presentation were excluded from the study.

The trial enrolled 659 patients from 29 sites in Brazil. The mean age of patients was 56 years, 40% were women, and 52% were obese. ACE inhibitors were being taken by 15% of the trial participants; ARBs were being taken by 85%. The median duration of ACE inhibitor/ARB treatment was 5 years.

Patients were a median of 6 days from COVID-19 symptom onset. For 30% of the patients, oxygen saturation was below 94% at entry. In terms of COVID-19 symptoms, 57% were classified as mild, and 43% as moderate.

Those with severe COVID-19 symptoms who needed intubation or vasoactive drugs were excluded. Antihypertensive therapy would generally be discontinued in these patients anyway, Dr. Lopes said.

Results showed that the average number of days alive and out of hospital was 21.9 days for patients who stopped taking ACE inhibitors/ARBs and 22.9 days for patients who continued taking these medications. The average difference between groups was –1.1 days.

The average ratio of days alive and out of hospital between the suspending and continuing groups was 0.95 (95% CI, 0.90-1.01; P = .09).

The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACE inhibitor/ARB group was 91.8% versus 95% in the continuing group.

A similar 30-day mortality rate was seen for patients who continued and those who suspended ACE inhibitor/ARB therapy, at 2.8% and 2.7%, respectively (hazard ratio, 0.97). The median number of days that patients were alive and out of hospital was 25 in both groups.

Dr. Lopes said that there was no difference between the two groups with regard to many other secondary outcomes. These included COVID-19 disease progression (need for intubation, ventilation, need for vasoactive drugs, or imaging results) and cardiovascular endpoints (MI, stroke, thromboembolic events, worsening heart failure, myocarditis, or hypertensive crisis).

“Our results endorse with reliable and more definitive data what most medical and cardiovascular societies are recommending – that patients do not stop ACE inhibitor or ARB medication. This has been based on observational data so far, but BRACE CORONA now provides randomized data to support this recommendation,” Dr. Lopes concluded.

Dr. Lopes noted that several subgroups had been prespecified for analysis. Factors included age, obesity, difference between ACE inhibitors/ARBs, difference in oxygen saturation at presentation, time since COVID-19 symptom onset, degree of lung involvement on CT, and symptom severity on presentation.

“We saw very consistent effects of our main findings across all these subgroups, and we plan to report more details of these in the near future,” he said.
 

Protective for older patients?

The discussant of the study at the ESC Hotline session, Gianfranco Parati, MD, University of Milan-Bicocca and San Luca Hospital, Milan, congratulated Lopes and his team for conducting this important trial at such a difficult time.

He pointed out that patients in the BRACE CORONA trial were quite young (average age, 56 years) and that observational data so far suggest that ACE inhibitors and ARBs have a stronger protective effect in older COVID-19 patients.

He also noted that the percentage of patients alive and out of hospital at 30 days was higher for the patients who continued on treatment in this study (95% vs. 91.8%), which suggested an advantage in maintaining the medication.

Dr. Lopes replied that one-quarter of the population in the BRACE CORONA trial was older than 65 years, which he said was a “reasonable number.”

“Subgroup analysis by age did not show a significant interaction, but the effect of continuing treatment does seem to be more favorable in older patients and also in those who were sicker and had more comorbidities,” he added.

Dr. Parati also suggested that it would have been difficult to discern differences between ACE inhibitors and ARBs in the BRACE CORONA trial, because so few patents were taking ACE inhibitors; the follow-up period of 30 days was relatively short, inasmuch as these drugs may have long-term effects; and it would have been difficult to show differences in the main outcomes used in the study – mortality and time out of hospital – in these patients with mild to moderate disease.

Franz H. Messerli, MD, and Christoph Gräni, MD, University of Bern (Switzerland), said in a joint statement: “The BRACE CORONA trial provides answers to what we know from retrospective studies: if you have already COVID, don’t stop renin-angiotensin system blocker medication.”

But they added that the study does not answer the question about the risk/benefit of ACE inhibitors or ARBs with regard to possible enhanced viral entry through the ACE2 receptor. “What about all those on these drugs who are not infected with COVID? Do they need to stop them? We simply don’t know yet,” they said.

Dr. Messerli and Dr. Gräni added that they would like to see a study that compared patients before SARS-CoV-2 infection who were without hypertension, patients with hypertension who were taking ACE inhibitors or ARBs, and patients with hypertension taking other antihypertensive drugs.

The BRACE CORONA trial was sponsored by D’Or Institute for Research and Education and the Brazilian Clinical Research Institute. Dr. Lopes has disclosed no relevant financial relationships.

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

A new analysis of existing research confirms a stark link between excess weight and COVID-19: People with obesity are much more likely to be diagnosed with the novel coronavirus, undergo hospitalization and ICU admission, and die.

Obese patients faced the greatest bump in risk on the hospitalization front, with their odds of being admitted listed as 113% higher. The odds of diagnosis, ICU admission, and death were 46% higher (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.30-1.65; P < .0001); 74% higher (OR, 1.74, CI, 1.46-2.08, P < .0001); 48% (OR, 1.48, CI, 1.22–1.80, P < .001, all pooled analyses and 95% CI), respectively. All differences were highly significantly different, investigators reported in a systematic review and meta-analysis published online Aug. 26 in Obesity Reviews.

“Essentially, these are pretty scary statistics,” nutrition researcher and study lead author Barry M. Popkin, PhD, of the University of North Carolina at Chapel Hill School of Public Health, said in an interview. “Other studies have talked about an increase in mortality, and we were thinking there’d be a little increase like 10% – nothing like 48%.”

According to the Johns Hopkins University of Medicine tracker, nearly 6 million people in the United States had been diagnosed with COVID-19 as of Aug. 30. The number of deaths had surpassed 183,000.

The authors of the new review launched their project to better understand the link between obesity and COVID-19 “all the way from being diagnosed to death,” Dr. Popkin said, adding that the meta-analysis is the largest of its kind to examine the link.

Dr. Popkin and colleagues analyzed 75 studies during January to June 2020 that tracked 399,461 patients (55% of whom were male) diagnosed with COVID-19. They found that 18 of 20 studies linked obesity with a 46% higher risk of diagnosis, but Dr. Popkin cautioned that this may be misleading. “I suspect it’s because they’re sicker and getting tested more for COVID,” he said. “I don’t think obesity enhances your likelihood of getting COVID. We don’t have a biological rationale for that.”

The researchers examined 19 studies that explored a link between obesity and hospitalization; all 19 found a higher risk of hospitalization in patients with obesity (pooled OR, 2.13). Twenty-one of 22 studies that looked at ICU admissions discovered a higher risk for patients with obesity (pooled OR, 1.74). And 27 of 35 studies that examined COVID-19 mortality found a higher death rate in patients with obesity (pooled OR, 1.48).

The review also looked at 14 studies that examined links between obesity and administration of invasive mechanical ventilation. All the studies found a higher risk for patients with obesity (pooled OR, 1.66; 95% CI, 1.38-1.99; P < .0001).

Could socioeconomic factors explain the difference in risk for people with obesity? It’s not clear. According to Dr. Popkin, most of the studies don’t examine factors such as income. While he believes physical factors are the key to the higher risk, he said “there’s clearly a social side to this.”

On the biological front, it appears that “the immune system is much weaker if you’re obese,” he said, and excess weight may worsen the course of a respiratory disease such as COVID-19 because of lung disorders such as sleep apnea.

In addition to highlighting inflammation and a weakened immune system, the review offers multiple explanations for why patients with obesity face worse outcomes in COVID-19. It may be more difficult for medical professionals to care for them in the hospital because of their weight, the authors wrote, and “obesity may also impair therapeutic treatments during COVID-19 infections.” The authors noted that ACE inhibitors may worsen COVID-19 in patients with type 2 diabetes.

The researchers noted that “potentially the vaccines developed to address COVID-19 will be less effective for individuals with obesity due to a weakened immune response.” They pointed to research that suggests T-cell responses are weaker and antibody titers wane at a faster rate in people with obesity who are vaccinated against influenza.

SOURCE: Popkin BM et al. Obes Rev. 2020 Aug 26. doi: 10.1111/obr.13128.

A new analysis of existing research confirms a stark link between excess weight and COVID-19: People with obesity are much more likely to be diagnosed with the novel coronavirus, undergo hospitalization and ICU admission, and die.

Obese patients faced the greatest bump in risk on the hospitalization front, with their odds of being admitted listed as 113% higher. The odds of diagnosis, ICU admission, and death were 46% higher (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.30-1.65; P < .0001); 74% higher (OR, 1.74, CI, 1.46-2.08, P < .0001); 48% (OR, 1.48, CI, 1.22–1.80, P < .001, all pooled analyses and 95% CI), respectively. All differences were highly significantly different, investigators reported in a systematic review and meta-analysis published online Aug. 26 in Obesity Reviews.

“Essentially, these are pretty scary statistics,” nutrition researcher and study lead author Barry M. Popkin, PhD, of the University of North Carolina at Chapel Hill School of Public Health, said in an interview. “Other studies have talked about an increase in mortality, and we were thinking there’d be a little increase like 10% – nothing like 48%.”

According to the Johns Hopkins University of Medicine tracker, nearly 6 million people in the United States had been diagnosed with COVID-19 as of Aug. 30. The number of deaths had surpassed 183,000.

The authors of the new review launched their project to better understand the link between obesity and COVID-19 “all the way from being diagnosed to death,” Dr. Popkin said, adding that the meta-analysis is the largest of its kind to examine the link.

Dr. Popkin and colleagues analyzed 75 studies during January to June 2020 that tracked 399,461 patients (55% of whom were male) diagnosed with COVID-19. They found that 18 of 20 studies linked obesity with a 46% higher risk of diagnosis, but Dr. Popkin cautioned that this may be misleading. “I suspect it’s because they’re sicker and getting tested more for COVID,” he said. “I don’t think obesity enhances your likelihood of getting COVID. We don’t have a biological rationale for that.”

The researchers examined 19 studies that explored a link between obesity and hospitalization; all 19 found a higher risk of hospitalization in patients with obesity (pooled OR, 2.13). Twenty-one of 22 studies that looked at ICU admissions discovered a higher risk for patients with obesity (pooled OR, 1.74). And 27 of 35 studies that examined COVID-19 mortality found a higher death rate in patients with obesity (pooled OR, 1.48).

The review also looked at 14 studies that examined links between obesity and administration of invasive mechanical ventilation. All the studies found a higher risk for patients with obesity (pooled OR, 1.66; 95% CI, 1.38-1.99; P < .0001).

Could socioeconomic factors explain the difference in risk for people with obesity? It’s not clear. According to Dr. Popkin, most of the studies don’t examine factors such as income. While he believes physical factors are the key to the higher risk, he said “there’s clearly a social side to this.”

On the biological front, it appears that “the immune system is much weaker if you’re obese,” he said, and excess weight may worsen the course of a respiratory disease such as COVID-19 because of lung disorders such as sleep apnea.

In addition to highlighting inflammation and a weakened immune system, the review offers multiple explanations for why patients with obesity face worse outcomes in COVID-19. It may be more difficult for medical professionals to care for them in the hospital because of their weight, the authors wrote, and “obesity may also impair therapeutic treatments during COVID-19 infections.” The authors noted that ACE inhibitors may worsen COVID-19 in patients with type 2 diabetes.

The researchers noted that “potentially the vaccines developed to address COVID-19 will be less effective for individuals with obesity due to a weakened immune response.” They pointed to research that suggests T-cell responses are weaker and antibody titers wane at a faster rate in people with obesity who are vaccinated against influenza.

SOURCE: Popkin BM et al. Obes Rev. 2020 Aug 26. doi: 10.1111/obr.13128.

A new analysis of existing research confirms a stark link between excess weight and COVID-19: People with obesity are much more likely to be diagnosed with the novel coronavirus, undergo hospitalization and ICU admission, and die.

Obese patients faced the greatest bump in risk on the hospitalization front, with their odds of being admitted listed as 113% higher. The odds of diagnosis, ICU admission, and death were 46% higher (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.30-1.65; P < .0001); 74% higher (OR, 1.74, CI, 1.46-2.08, P < .0001); 48% (OR, 1.48, CI, 1.22–1.80, P < .001, all pooled analyses and 95% CI), respectively. All differences were highly significantly different, investigators reported in a systematic review and meta-analysis published online Aug. 26 in Obesity Reviews.

“Essentially, these are pretty scary statistics,” nutrition researcher and study lead author Barry M. Popkin, PhD, of the University of North Carolina at Chapel Hill School of Public Health, said in an interview. “Other studies have talked about an increase in mortality, and we were thinking there’d be a little increase like 10% – nothing like 48%.”

According to the Johns Hopkins University of Medicine tracker, nearly 6 million people in the United States had been diagnosed with COVID-19 as of Aug. 30. The number of deaths had surpassed 183,000.

The authors of the new review launched their project to better understand the link between obesity and COVID-19 “all the way from being diagnosed to death,” Dr. Popkin said, adding that the meta-analysis is the largest of its kind to examine the link.

Dr. Popkin and colleagues analyzed 75 studies during January to June 2020 that tracked 399,461 patients (55% of whom were male) diagnosed with COVID-19. They found that 18 of 20 studies linked obesity with a 46% higher risk of diagnosis, but Dr. Popkin cautioned that this may be misleading. “I suspect it’s because they’re sicker and getting tested more for COVID,” he said. “I don’t think obesity enhances your likelihood of getting COVID. We don’t have a biological rationale for that.”

The researchers examined 19 studies that explored a link between obesity and hospitalization; all 19 found a higher risk of hospitalization in patients with obesity (pooled OR, 2.13). Twenty-one of 22 studies that looked at ICU admissions discovered a higher risk for patients with obesity (pooled OR, 1.74). And 27 of 35 studies that examined COVID-19 mortality found a higher death rate in patients with obesity (pooled OR, 1.48).

The review also looked at 14 studies that examined links between obesity and administration of invasive mechanical ventilation. All the studies found a higher risk for patients with obesity (pooled OR, 1.66; 95% CI, 1.38-1.99; P < .0001).

Could socioeconomic factors explain the difference in risk for people with obesity? It’s not clear. According to Dr. Popkin, most of the studies don’t examine factors such as income. While he believes physical factors are the key to the higher risk, he said “there’s clearly a social side to this.”

On the biological front, it appears that “the immune system is much weaker if you’re obese,” he said, and excess weight may worsen the course of a respiratory disease such as COVID-19 because of lung disorders such as sleep apnea.

In addition to highlighting inflammation and a weakened immune system, the review offers multiple explanations for why patients with obesity face worse outcomes in COVID-19. It may be more difficult for medical professionals to care for them in the hospital because of their weight, the authors wrote, and “obesity may also impair therapeutic treatments during COVID-19 infections.” The authors noted that ACE inhibitors may worsen COVID-19 in patients with type 2 diabetes.

The researchers noted that “potentially the vaccines developed to address COVID-19 will be less effective for individuals with obesity due to a weakened immune response.” They pointed to research that suggests T-cell responses are weaker and antibody titers wane at a faster rate in people with obesity who are vaccinated against influenza.

SOURCE: Popkin BM et al. Obes Rev. 2020 Aug 26. doi: 10.1111/obr.13128.

The pragmatic Hestia criteria proved as safe as the more structured, points-based simplified Pulmonary Embolism Severity Index (sPESI) score for selection of patients with acute pulmonary embolism for outpatient care in the large, randomized HOME-PE trial presented at the virtual annual congress of the European Society of Cardiology.

Courtesy Wikimedia Commons/Walter Serra, Giuseppe De Iaco, Claudio Reverberi, and Tiziano Gherli/Creative Commons License

“These results support outpatient management of acute pulmonary embolism patients using either the Hestia method or the sPESI score with the option for the physician-in-charge to override the decision. In hospitals organized for outpatient management, both triaging strategies enable more than a third of pulmonary embolism patients to be managed at home with a low rate of complications,” Pierre-Marie Roy, MD, said in presenting the HOME-PE findings.

The study clarifies a transatlantic controversy regarding how best to triage patients with acute pulmonary embolism (PE) for outpatient care. The answer? It’s basically a tie between the points-based sPESI score recommended in the current ESC guidelines (Eur Respir J. 2019 Oct 9;54[3]:1901647) and the Hestia method endorsed in the American College of Chest Physician guidelines (Chest. 2016 Feb;149[2]:315-52).

The sPESI is a validated tool that grants 1 point each for age over 80 years, background cardiopulmonary disease, a systolic blood pressure below 100 mm Hg, cancer, a heart rate of 110 bpm or more, and an oxygen saturation level below 90%. A patient needs a score of zero to be eligible for outpatient management. In contrast, the Hestia method relies upon 11 simple bedside criteria rather than a points system, explained Dr. Roy of University Hospital of Angers, France (J Thromb Haemost. 2011 Aug;9[8]:1500-7).

HOME-PE was a randomized, open-label, noninferiority trial conducted at 26 hospitals in France, Belgium, Switzerland, and the Netherlands. The study included 1,974 patients presenting to the emergency department with non–high-risk acute PE as defined by hemodynamic stability. About 39% of patients in the Hestia group were eligible for outpatient care on the basis of ‘no’ answers regarding all 11 criteria, while 48% of patients had an sPESI score of 0 and were thus initially considered appropriate for outpatient management.

However, the investigators recognized that no scoring system for acute PE is perfect, and that the judgment of a physician with extensive experience in managing this life-threatening condition counts for a lot. So they stipulated that a patient’s physician-in-charge could overrule a decision for early discharge. This happened 29% of the time in patients with a sPESI score of 0, as compared with a 3% overrule rate with the Hestia rule. The physician-in-charge also moved small numbers of patients who were Hestia or sPESI positive into the outpatient care group. As a result, a similar proportion of patients in both groups were discharged home within 24 hours for outpatient treatment: 38% of the total Hestia group and 37% in the sPESI arm.

Major adverse event rates were reassuringly low in both groups managed on an outpatient basis. The composite of recurrent venous thromboembolism, bleeding, or death within 30 days occurred in 1.3% of Hestia outpatients and 1.1% of sPESI outpatients. Among patients managed in the hospital, these rates were 5.6% in the Hestia group and 4.7% in the sPESI group.

Discussant Stavros V. Konstantinides, MD, who chaired the ESC guideline committee, asked rhetorically, “who’s happy with the HOME-PE trial? I think everybody.”

“The Hestia criteria integrate the feasibility of family support of the individual patient. This is a good thing. And eligibility based on the Hestia criteria, unlike sPESI, does not require age younger than 80 years or no cancer, and it appears from the HOME-PE study that this is okay,” observed Dr. Konstantinides of the Center for Thrombosis and Hemostasis at the University of Mainz (Germany).

In an interview, Hadley Wilson, MD, called the HOME-PE trial “transformative” and predicted it will change clinical practice. He was particularly impressed with the high quality of the trial, noting that 87% of participants managed as outpatients received a direct oral anticoagulant.

The Hestia rule is simpler and more user-friendly. And greater use of this triaging strategy might have advantages in terms of economics and health care utilization by potentially encouraging movement of decision-making regarding outpatient management of acute PE out of the hospital wards and into emergency departments, said Dr. Wilson, executive vice chair of the Sanger Heart and Vascular Institute and a cardiologist at the University of North Carolina at Chapel Hill.

Dr. Roy reported receiving research grants to conduct HOME-PE from the French Ministry of Health, the study sponsor. In addition, he is on scientific advisory boards and/or speakers’ panels for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Aspen, Daiichi Sankyo, and Sanofi Aventis.
 

[email protected]

The pragmatic Hestia criteria proved as safe as the more structured, points-based simplified Pulmonary Embolism Severity Index (sPESI) score for selection of patients with acute pulmonary embolism for outpatient care in the large, randomized HOME-PE trial presented at the virtual annual congress of the European Society of Cardiology.

Courtesy Wikimedia Commons/Walter Serra, Giuseppe De Iaco, Claudio Reverberi, and Tiziano Gherli/Creative Commons License

“These results support outpatient management of acute pulmonary embolism patients using either the Hestia method or the sPESI score with the option for the physician-in-charge to override the decision. In hospitals organized for outpatient management, both triaging strategies enable more than a third of pulmonary embolism patients to be managed at home with a low rate of complications,” Pierre-Marie Roy, MD, said in presenting the HOME-PE findings.

The study clarifies a transatlantic controversy regarding how best to triage patients with acute pulmonary embolism (PE) for outpatient care. The answer? It’s basically a tie between the points-based sPESI score recommended in the current ESC guidelines (Eur Respir J. 2019 Oct 9;54[3]:1901647) and the Hestia method endorsed in the American College of Chest Physician guidelines (Chest. 2016 Feb;149[2]:315-52).

The sPESI is a validated tool that grants 1 point each for age over 80 years, background cardiopulmonary disease, a systolic blood pressure below 100 mm Hg, cancer, a heart rate of 110 bpm or more, and an oxygen saturation level below 90%. A patient needs a score of zero to be eligible for outpatient management. In contrast, the Hestia method relies upon 11 simple bedside criteria rather than a points system, explained Dr. Roy of University Hospital of Angers, France (J Thromb Haemost. 2011 Aug;9[8]:1500-7).

HOME-PE was a randomized, open-label, noninferiority trial conducted at 26 hospitals in France, Belgium, Switzerland, and the Netherlands. The study included 1,974 patients presenting to the emergency department with non–high-risk acute PE as defined by hemodynamic stability. About 39% of patients in the Hestia group were eligible for outpatient care on the basis of ‘no’ answers regarding all 11 criteria, while 48% of patients had an sPESI score of 0 and were thus initially considered appropriate for outpatient management.

However, the investigators recognized that no scoring system for acute PE is perfect, and that the judgment of a physician with extensive experience in managing this life-threatening condition counts for a lot. So they stipulated that a patient’s physician-in-charge could overrule a decision for early discharge. This happened 29% of the time in patients with a sPESI score of 0, as compared with a 3% overrule rate with the Hestia rule. The physician-in-charge also moved small numbers of patients who were Hestia or sPESI positive into the outpatient care group. As a result, a similar proportion of patients in both groups were discharged home within 24 hours for outpatient treatment: 38% of the total Hestia group and 37% in the sPESI arm.

Major adverse event rates were reassuringly low in both groups managed on an outpatient basis. The composite of recurrent venous thromboembolism, bleeding, or death within 30 days occurred in 1.3% of Hestia outpatients and 1.1% of sPESI outpatients. Among patients managed in the hospital, these rates were 5.6% in the Hestia group and 4.7% in the sPESI group.

Discussant Stavros V. Konstantinides, MD, who chaired the ESC guideline committee, asked rhetorically, “who’s happy with the HOME-PE trial? I think everybody.”

“The Hestia criteria integrate the feasibility of family support of the individual patient. This is a good thing. And eligibility based on the Hestia criteria, unlike sPESI, does not require age younger than 80 years or no cancer, and it appears from the HOME-PE study that this is okay,” observed Dr. Konstantinides of the Center for Thrombosis and Hemostasis at the University of Mainz (Germany).

In an interview, Hadley Wilson, MD, called the HOME-PE trial “transformative” and predicted it will change clinical practice. He was particularly impressed with the high quality of the trial, noting that 87% of participants managed as outpatients received a direct oral anticoagulant.

The Hestia rule is simpler and more user-friendly. And greater use of this triaging strategy might have advantages in terms of economics and health care utilization by potentially encouraging movement of decision-making regarding outpatient management of acute PE out of the hospital wards and into emergency departments, said Dr. Wilson, executive vice chair of the Sanger Heart and Vascular Institute and a cardiologist at the University of North Carolina at Chapel Hill.

Dr. Roy reported receiving research grants to conduct HOME-PE from the French Ministry of Health, the study sponsor. In addition, he is on scientific advisory boards and/or speakers’ panels for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Aspen, Daiichi Sankyo, and Sanofi Aventis.
 

[email protected]

The pragmatic Hestia criteria proved as safe as the more structured, points-based simplified Pulmonary Embolism Severity Index (sPESI) score for selection of patients with acute pulmonary embolism for outpatient care in the large, randomized HOME-PE trial presented at the virtual annual congress of the European Society of Cardiology.

Courtesy Wikimedia Commons/Walter Serra, Giuseppe De Iaco, Claudio Reverberi, and Tiziano Gherli/Creative Commons License

“These results support outpatient management of acute pulmonary embolism patients using either the Hestia method or the sPESI score with the option for the physician-in-charge to override the decision. In hospitals organized for outpatient management, both triaging strategies enable more than a third of pulmonary embolism patients to be managed at home with a low rate of complications,” Pierre-Marie Roy, MD, said in presenting the HOME-PE findings.

The study clarifies a transatlantic controversy regarding how best to triage patients with acute pulmonary embolism (PE) for outpatient care. The answer? It’s basically a tie between the points-based sPESI score recommended in the current ESC guidelines (Eur Respir J. 2019 Oct 9;54[3]:1901647) and the Hestia method endorsed in the American College of Chest Physician guidelines (Chest. 2016 Feb;149[2]:315-52).

The sPESI is a validated tool that grants 1 point each for age over 80 years, background cardiopulmonary disease, a systolic blood pressure below 100 mm Hg, cancer, a heart rate of 110 bpm or more, and an oxygen saturation level below 90%. A patient needs a score of zero to be eligible for outpatient management. In contrast, the Hestia method relies upon 11 simple bedside criteria rather than a points system, explained Dr. Roy of University Hospital of Angers, France (J Thromb Haemost. 2011 Aug;9[8]:1500-7).

HOME-PE was a randomized, open-label, noninferiority trial conducted at 26 hospitals in France, Belgium, Switzerland, and the Netherlands. The study included 1,974 patients presenting to the emergency department with non–high-risk acute PE as defined by hemodynamic stability. About 39% of patients in the Hestia group were eligible for outpatient care on the basis of ‘no’ answers regarding all 11 criteria, while 48% of patients had an sPESI score of 0 and were thus initially considered appropriate for outpatient management.

However, the investigators recognized that no scoring system for acute PE is perfect, and that the judgment of a physician with extensive experience in managing this life-threatening condition counts for a lot. So they stipulated that a patient’s physician-in-charge could overrule a decision for early discharge. This happened 29% of the time in patients with a sPESI score of 0, as compared with a 3% overrule rate with the Hestia rule. The physician-in-charge also moved small numbers of patients who were Hestia or sPESI positive into the outpatient care group. As a result, a similar proportion of patients in both groups were discharged home within 24 hours for outpatient treatment: 38% of the total Hestia group and 37% in the sPESI arm.

Major adverse event rates were reassuringly low in both groups managed on an outpatient basis. The composite of recurrent venous thromboembolism, bleeding, or death within 30 days occurred in 1.3% of Hestia outpatients and 1.1% of sPESI outpatients. Among patients managed in the hospital, these rates were 5.6% in the Hestia group and 4.7% in the sPESI group.

Discussant Stavros V. Konstantinides, MD, who chaired the ESC guideline committee, asked rhetorically, “who’s happy with the HOME-PE trial? I think everybody.”

“The Hestia criteria integrate the feasibility of family support of the individual patient. This is a good thing. And eligibility based on the Hestia criteria, unlike sPESI, does not require age younger than 80 years or no cancer, and it appears from the HOME-PE study that this is okay,” observed Dr. Konstantinides of the Center for Thrombosis and Hemostasis at the University of Mainz (Germany).

In an interview, Hadley Wilson, MD, called the HOME-PE trial “transformative” and predicted it will change clinical practice. He was particularly impressed with the high quality of the trial, noting that 87% of participants managed as outpatients received a direct oral anticoagulant.

The Hestia rule is simpler and more user-friendly. And greater use of this triaging strategy might have advantages in terms of economics and health care utilization by potentially encouraging movement of decision-making regarding outpatient management of acute PE out of the hospital wards and into emergency departments, said Dr. Wilson, executive vice chair of the Sanger Heart and Vascular Institute and a cardiologist at the University of North Carolina at Chapel Hill.

Dr. Roy reported receiving research grants to conduct HOME-PE from the French Ministry of Health, the study sponsor. In addition, he is on scientific advisory boards and/or speakers’ panels for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Aspen, Daiichi Sankyo, and Sanofi Aventis.
 

[email protected]

The PCSK9 monoclonal antibody evolocumab (Repatha) was well tolerated and effectively lowered LDL cholesterol by 38% compared with placebo in a randomized controlled trial in pediatric patients with heterozygous familial hypercholesterolemia (FH) already taking statins with or without ezetimibe.

“HAUSER-RCT is the largest study and the first placebo-controlled randomized trial of a PCSK9 inhibitor in pediatric FH,” senior author Daniel Gaudet, MD, PhD, Universite de Montreal, said in an interview.

“The study showed good safety and efficacy of the drug in this population, with an excellent 44% reduction in LDL cholesterol compared with 6% in the placebo group.”

The trial also found evolocumab to be well tolerated in this group, with adverse effects similar in the active and placebo groups. 

“Some people have wondered about using a drug with a monthly injection in a pediatric population, but this was not an issue in our study,” Dr. Gaudet said. “The idea of a monthly injection was well received, and no patient withdrew because of this.”

The HAUSER-RCT trial was presented on Aug. 29 at the virtual annual congress of the European Society of Cardiology (ESC Congress 2020) and simultaneously published online in the New England Journal of Medicine.

“With patients recruited from 23 countries in five continents, the study provides an accurate picture of the safety and efficacy of evolocumab in pediatric FH patients worldwide,” Dr. Gaudet said.  

The 24-week, randomized, double-blind, placebo-controlled trial involved 157 patients aged 10-17 years with heterozygous FH already taking statins with or without ezetimibe and who had an LDL cholesterol level of 130 mg/dL or more and a triglyceride level of 400 mg/dL or less.

They were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo.

Results showed that at week 24, the mean percentage change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, giving a difference of −38.3 percentage points (P < .001).

The absolute change in the LDL cholesterol level was −77.5 mg/dL in the evolocumab group and −9.0 mg/dL in the placebo group, giving a difference of −68.6 mg/dL (P < .001).

Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. Laboratory abnormalities did not differ between groups.

Dr. Gaudet noted that FH is the most common genetic disease worldwide, affecting 1 in 250 people. “It is very treatable, so it is important to identify these patients, but it is massively underdiagnosed, with only around 15%-20% of patients with the condition having been identified,” he said.

“The vast majority of pediatric FH patients can reach target LDL levels with statins and ezetimibe, but there are 5%-10% of patients who may need additional therapy. We have now shown that evolocumab is safe and effective for these patients and can be used to fill this gap,” Dr. Gaudet said. “We can now say that we can cover all situations in treating FH whatever the severity of the disease.”

However, the challenge remains to improve the diagnosis of FH.  “If there is one person with FH in a family, then it is essential that the whole extended family is tested. Our toolbox for treating this condition is now sufficiently effective, so there is no reason not to diagnose this disease,” Dr. Gaudet stressed.  

The HAUSER-RCT study was supported by Amgen. Gaudet reports grants and personal fees from Amgen during the conduct of the study.

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

The PCSK9 monoclonal antibody evolocumab (Repatha) was well tolerated and effectively lowered LDL cholesterol by 38% compared with placebo in a randomized controlled trial in pediatric patients with heterozygous familial hypercholesterolemia (FH) already taking statins with or without ezetimibe.

“HAUSER-RCT is the largest study and the first placebo-controlled randomized trial of a PCSK9 inhibitor in pediatric FH,” senior author Daniel Gaudet, MD, PhD, Universite de Montreal, said in an interview.

“The study showed good safety and efficacy of the drug in this population, with an excellent 44% reduction in LDL cholesterol compared with 6% in the placebo group.”

The trial also found evolocumab to be well tolerated in this group, with adverse effects similar in the active and placebo groups. 

“Some people have wondered about using a drug with a monthly injection in a pediatric population, but this was not an issue in our study,” Dr. Gaudet said. “The idea of a monthly injection was well received, and no patient withdrew because of this.”

The HAUSER-RCT trial was presented on Aug. 29 at the virtual annual congress of the European Society of Cardiology (ESC Congress 2020) and simultaneously published online in the New England Journal of Medicine.

“With patients recruited from 23 countries in five continents, the study provides an accurate picture of the safety and efficacy of evolocumab in pediatric FH patients worldwide,” Dr. Gaudet said.  

The 24-week, randomized, double-blind, placebo-controlled trial involved 157 patients aged 10-17 years with heterozygous FH already taking statins with or without ezetimibe and who had an LDL cholesterol level of 130 mg/dL or more and a triglyceride level of 400 mg/dL or less.

They were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo.

Results showed that at week 24, the mean percentage change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, giving a difference of −38.3 percentage points (P < .001).

The absolute change in the LDL cholesterol level was −77.5 mg/dL in the evolocumab group and −9.0 mg/dL in the placebo group, giving a difference of −68.6 mg/dL (P < .001).

Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. Laboratory abnormalities did not differ between groups.

Dr. Gaudet noted that FH is the most common genetic disease worldwide, affecting 1 in 250 people. “It is very treatable, so it is important to identify these patients, but it is massively underdiagnosed, with only around 15%-20% of patients with the condition having been identified,” he said.

“The vast majority of pediatric FH patients can reach target LDL levels with statins and ezetimibe, but there are 5%-10% of patients who may need additional therapy. We have now shown that evolocumab is safe and effective for these patients and can be used to fill this gap,” Dr. Gaudet said. “We can now say that we can cover all situations in treating FH whatever the severity of the disease.”

However, the challenge remains to improve the diagnosis of FH.  “If there is one person with FH in a family, then it is essential that the whole extended family is tested. Our toolbox for treating this condition is now sufficiently effective, so there is no reason not to diagnose this disease,” Dr. Gaudet stressed.  

The HAUSER-RCT study was supported by Amgen. Gaudet reports grants and personal fees from Amgen during the conduct of the study.

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

The PCSK9 monoclonal antibody evolocumab (Repatha) was well tolerated and effectively lowered LDL cholesterol by 38% compared with placebo in a randomized controlled trial in pediatric patients with heterozygous familial hypercholesterolemia (FH) already taking statins with or without ezetimibe.

“HAUSER-RCT is the largest study and the first placebo-controlled randomized trial of a PCSK9 inhibitor in pediatric FH,” senior author Daniel Gaudet, MD, PhD, Universite de Montreal, said in an interview.

“The study showed good safety and efficacy of the drug in this population, with an excellent 44% reduction in LDL cholesterol compared with 6% in the placebo group.”

The trial also found evolocumab to be well tolerated in this group, with adverse effects similar in the active and placebo groups. 

“Some people have wondered about using a drug with a monthly injection in a pediatric population, but this was not an issue in our study,” Dr. Gaudet said. “The idea of a monthly injection was well received, and no patient withdrew because of this.”

The HAUSER-RCT trial was presented on Aug. 29 at the virtual annual congress of the European Society of Cardiology (ESC Congress 2020) and simultaneously published online in the New England Journal of Medicine.

“With patients recruited from 23 countries in five continents, the study provides an accurate picture of the safety and efficacy of evolocumab in pediatric FH patients worldwide,” Dr. Gaudet said.  

The 24-week, randomized, double-blind, placebo-controlled trial involved 157 patients aged 10-17 years with heterozygous FH already taking statins with or without ezetimibe and who had an LDL cholesterol level of 130 mg/dL or more and a triglyceride level of 400 mg/dL or less.

They were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo.

Results showed that at week 24, the mean percentage change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, giving a difference of −38.3 percentage points (P < .001).

The absolute change in the LDL cholesterol level was −77.5 mg/dL in the evolocumab group and −9.0 mg/dL in the placebo group, giving a difference of −68.6 mg/dL (P < .001).

Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. Laboratory abnormalities did not differ between groups.

Dr. Gaudet noted that FH is the most common genetic disease worldwide, affecting 1 in 250 people. “It is very treatable, so it is important to identify these patients, but it is massively underdiagnosed, with only around 15%-20% of patients with the condition having been identified,” he said.

“The vast majority of pediatric FH patients can reach target LDL levels with statins and ezetimibe, but there are 5%-10% of patients who may need additional therapy. We have now shown that evolocumab is safe and effective for these patients and can be used to fill this gap,” Dr. Gaudet said. “We can now say that we can cover all situations in treating FH whatever the severity of the disease.”

However, the challenge remains to improve the diagnosis of FH.  “If there is one person with FH in a family, then it is essential that the whole extended family is tested. Our toolbox for treating this condition is now sufficiently effective, so there is no reason not to diagnose this disease,” Dr. Gaudet stressed.  

The HAUSER-RCT study was supported by Amgen. Gaudet reports grants and personal fees from Amgen during the conduct of the study.

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

Adding trimetazidine to optimal medical therapy does not improve outcomes following successful percutaneous coronary intervention (PCI) for stable angina or a non–ST-elevated myocardial infarction, results of the ATPCI trial show.

There was no benefit for the composite primary endpoint of cardiac death, hospitalization for cardiac events, or recurrent/persistent angina requiring an addition, switch, or increased dose of antianginal therapies, or requiring coronary angiography (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09).

• Cardiac death: 2.1% vs. 2.6% (HR, 0.81)
• Hospital admission for cardiac events: 13.4% vs. 13.4% (HR, 1.01)
• Angina leading to coronary angiography: 16.9% vs. 16.6% (HR, 1.02)
• Angina leading to increase/switch in antianginal drugs (HR, 1.01)

There was no between-group difference in the composite major secondary endpoint, which included the primary endpoint components plus ischemia leading to coronary angiography and an increase or switch in antianginal therapies. This outcome occurred in 23.5% and 24.0% of patients in the trimetazidine and control groups, respectively (HR, 0.98; 95% CI, 0.88-1.08).

Results were also similar when the primary endpoint was analyzed based on whether patients underwent elective PCI (HR, 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR, 1.04; 95% CI, 0.88-1.22), Dr. Ferrari reported.

Given the lack of observed efficacy, trimetazidine has no use or place in the population studied, said Stephan Windecker, MD, the formal discussant for the study and chair of cardiology at Bern (Switzerland) University Hospital. “Notwithstanding, I think we have to recognize that the optimal medical therapy is so potent and has been well implemented in this trial that any additional medication beyond this is just unable to exploit additional benefit.”

The study was supported by Servier. Dr. Ferrari received fees, honoraria, and travel expenses from Servier. Dr. Ohman reports no relevant financial conflicts of interest. Dr. Windecker is an unpaid member of the steering/executive group for trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliancé, Medtronic, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments from any pharmaceutical or device company.

This article first appeared on Medscape.com.

Adding trimetazidine to optimal medical therapy does not improve outcomes following successful percutaneous coronary intervention (PCI) for stable angina or a non–ST-elevated myocardial infarction, results of the ATPCI trial show.

There was no benefit for the composite primary endpoint of cardiac death, hospitalization for cardiac events, or recurrent/persistent angina requiring an addition, switch, or increased dose of antianginal therapies, or requiring coronary angiography (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09).

• Cardiac death: 2.1% vs. 2.6% (HR, 0.81)
• Hospital admission for cardiac events: 13.4% vs. 13.4% (HR, 1.01)
• Angina leading to coronary angiography: 16.9% vs. 16.6% (HR, 1.02)
• Angina leading to increase/switch in antianginal drugs (HR, 1.01)

There was no between-group difference in the composite major secondary endpoint, which included the primary endpoint components plus ischemia leading to coronary angiography and an increase or switch in antianginal therapies. This outcome occurred in 23.5% and 24.0% of patients in the trimetazidine and control groups, respectively (HR, 0.98; 95% CI, 0.88-1.08).

Results were also similar when the primary endpoint was analyzed based on whether patients underwent elective PCI (HR, 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR, 1.04; 95% CI, 0.88-1.22), Dr. Ferrari reported.

Given the lack of observed efficacy, trimetazidine has no use or place in the population studied, said Stephan Windecker, MD, the formal discussant for the study and chair of cardiology at Bern (Switzerland) University Hospital. “Notwithstanding, I think we have to recognize that the optimal medical therapy is so potent and has been well implemented in this trial that any additional medication beyond this is just unable to exploit additional benefit.”

The study was supported by Servier. Dr. Ferrari received fees, honoraria, and travel expenses from Servier. Dr. Ohman reports no relevant financial conflicts of interest. Dr. Windecker is an unpaid member of the steering/executive group for trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliancé, Medtronic, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments from any pharmaceutical or device company.

This article first appeared on Medscape.com.

Adding trimetazidine to optimal medical therapy does not improve outcomes following successful percutaneous coronary intervention (PCI) for stable angina or a non–ST-elevated myocardial infarction, results of the ATPCI trial show.

There was no benefit for the composite primary endpoint of cardiac death, hospitalization for cardiac events, or recurrent/persistent angina requiring an addition, switch, or increased dose of antianginal therapies, or requiring coronary angiography (hazard ratio, 0.98; 95% confidence interval, 0.88-1.09).

• Cardiac death: 2.1% vs. 2.6% (HR, 0.81)
• Hospital admission for cardiac events: 13.4% vs. 13.4% (HR, 1.01)
• Angina leading to coronary angiography: 16.9% vs. 16.6% (HR, 1.02)
• Angina leading to increase/switch in antianginal drugs (HR, 1.01)

There was no between-group difference in the composite major secondary endpoint, which included the primary endpoint components plus ischemia leading to coronary angiography and an increase or switch in antianginal therapies. This outcome occurred in 23.5% and 24.0% of patients in the trimetazidine and control groups, respectively (HR, 0.98; 95% CI, 0.88-1.08).

Results were also similar when the primary endpoint was analyzed based on whether patients underwent elective PCI (HR, 0.94; 95% CI, 0.82-1.08) or urgent PCI (HR, 1.04; 95% CI, 0.88-1.22), Dr. Ferrari reported.

Given the lack of observed efficacy, trimetazidine has no use or place in the population studied, said Stephan Windecker, MD, the formal discussant for the study and chair of cardiology at Bern (Switzerland) University Hospital. “Notwithstanding, I think we have to recognize that the optimal medical therapy is so potent and has been well implemented in this trial that any additional medication beyond this is just unable to exploit additional benefit.”

The study was supported by Servier. Dr. Ferrari received fees, honoraria, and travel expenses from Servier. Dr. Ohman reports no relevant financial conflicts of interest. Dr. Windecker is an unpaid member of the steering/executive group for trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliancé, Medtronic, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments from any pharmaceutical or device company.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

The US Food and Drug Administration has removed two senior public relations employees, one of whom advised the agency against unbridled promotion of convalescent blood plasma as a treatment for people with COVID-19, multiple media outlets reported Aug. 28.

Officials claim the dismissals are coincidental and are not related to a controversy about whether claims regarding convalescent plasma therapy that were put forth by President Donald Trump and FDA Commissioner Stephen M. Hahn, MD, were exaggerated, according to reports from The New York Times , CNN, and elsewhere.

One of the PR employees, Emily Miller, was on the job less than 2 weeks. The White House named her FDA chief spokeswoman 11 days ago, but Hahn removed her from that post Aug. 28.

On Aug. 27, the US Department of Health and Human Services terminated the contract for Wayne L. Pines, a PR consultant to the FDA. Pines reportedly advised Hahn to apologize for making misleading claims about the therapeutic benefits of convalescent plasma therapy for COVID-19.

The FDA did not respond to multiple requests for comment.

The controversy stems from comments Hahn made about the announcement of the emergency use authorization for convalescent plasma for patients with COVID-19. He said that plasma had been found to save the lives of 35 out of every 100 people who were treated. That statement was later found to be erroneous because he presented a relative risk reduction as an absolute decrease in risk. He later apologized via Twitter.

Researchers running clinical trials to evaluate the efficacy of convalescent plasma for COVID-19 are concerned that the emergency use authorization could thwart efforts to recruit participants for their studies.

This article first appeared on Medscape.com.

Add patients with chronic kidney disease with or without diabetes to the growing list of people who get proven benefit from treatment with an SGLT2 inhibitor.

Courtesy European Society of Cardiology

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.

The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.

“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”

This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.

The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
 

Representing many real-world patients

The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m²), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.

This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.

Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m², pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m², but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.

“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”

A heart-kidney connection

Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.

“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.

[email protected]

Add patients with chronic kidney disease with or without diabetes to the growing list of people who get proven benefit from treatment with an SGLT2 inhibitor.

Courtesy European Society of Cardiology

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.

The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.

“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”

This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.

The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
 

Representing many real-world patients

The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m²), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.

This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.

Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m², pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m², but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.

“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”

A heart-kidney connection

Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.

“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.

[email protected]

Add patients with chronic kidney disease with or without diabetes to the growing list of people who get proven benefit from treatment with an SGLT2 inhibitor.

Courtesy European Society of Cardiology

In the DAPA-CKD trial, treatment with the SGLT2 inhibitor dapagliflozin (Farxiga) cut the incidence of substantially worsened chronic kidney disease by an average of 39% compared with placebo when added to standard treatment, with a number needed to treat of 19 to prevent one primary outcome event after a median of 2.4 years.

The level of benefit was similar in both the one-third of enrolled patients without diabetes and in the two-thirds with diabetes, showing a statistically significant 50% cut in the primary endpoint among patients without diabetes, Hiddo J.L. Heerspink, MD, reported at the virtual annual congress of the European Society of Cardiology.

“We found that dapagliflozin delayed the initiation of dialysis, and reduced the number of deaths,” regardless of diabetes status, Dr. Heerspink, of University Medical Centre Groningen, the Netherlands, said during a press conference. “DAPA-CKD trial has shown dapagliflozin’s potential as a long-awaited new treatment for patients with chronic kidney disease.”

This finding ushers in a “completely new era in chronic kidney disease management,” said Janani Rangaswami, MD, a nephrologist and cardiorenal syndrome specialist at Einstein Medical Center in Philadelphia. “It’s good news” for these patients.

The results showed that dapagliflozin is the first “game changing” drug for chronic kidney disease in 2 decades, following the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, she said in an interview. And given the consistency of the findings with the results from several other studies that documented meaningful renal protection by several different SGLT2 inhibitors, the results from this single trial also convincingly establish dapagliflozin as a standard-of-care agent to use on the types of patients the study enrolled, she said in an interview.
 

Representing many real-world patients

The DAPA-CKD trial enrolled 4,304 patients with albuminuria based on having a urinary albumin-to-creatinine ratio of at least 200 mg/g, and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1.73 m² (with 90% of patients having an eGFR of less than 60 mL/min per 1.73 m²), and 97% were on treatment with a renin-angiotensin system–blocking drug. The primary endpoint was the combined rate of a drop in eGFR of at least 50% from baseline, progression to end stage renal disease, or renal or cardiovascular death; the between-group difference in this composite was driven primarily by both preserved eGFR and by prevention of end stage renal disease.

This represents both an appropriate target population, and meaningful endpoints, Dr. Rangaswami said. The study was “very representative of who we see in real-world practice,” a group that likely includes “hundreds of thousands” of U.S. patients with nondiabetic chronic kidney disease, she estimated.

Another notable finding was that 14% of the enrolled patients had eGFR values at baseline of 25-29 mL/min per 1.73 m², pegging them as having stage 4 chronic kidney disease, and the median baseline eGFR was 43 mL/min per 1.73 m², but dapagliflozin treatment was as safe and effective in these patients as it was in enrolled patients with a higher level of retained renal activity. This experience should give clinicians greater confidence about using dapagliflozin and other drugs in the sodium-glucose cotransporter (SGLT) 2 inhibitor class in patients with substantially depressed renal function, Dr. Rangaswami said.

“We now need to be more proactive about treating patients with more advanced kidney disease who can still benefit” from dapagliflozin treatment. “The sooner you intervene the better,” to slow further progression, but the new findings show “benefit even when treating patients with lower eGFRs. There is still hope to prevent or delay dialysis.”

A heart-kidney connection

Dapagliflozin treatment also cut all-cause mortality by a statistically significant, relative 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization, a benefit seen consistently in several prior studies of SGLT2 inhibitors, but possibly unexpected here because enrolled patients underwent no selection for a history of heart failure or any other cardiovascular disease. But the finding shouldn’t surprise, because “chronic kidney disease is an independent risk factor for cardiovascular disease across the board, and especially for heart failure,” noted Dr. Rangaswami.

“Heart and kidney disease is one big spectrum,” and the collected experience of several trials that have now proven the efficacy of SGLT2 inhibitors among patients with heart failure with reduced ejection fraction or with chronic kidney disease, regardless of their glycemic control, shows how broadly this drug class can benefit patients across the breadth of this spectrum, she said.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Heerspink has been a consultant to and received research funding from AstraZeneca and from several other companies. Dr. Rangaswami had no disclosures.

[email protected]

Digoxin now deserves to be considered first-line therapy for long-term heart rate control in older patients with permanent atrial fibrillation and symptoms of heart failure, Dipak Kotecha, MBChB, PhD, MSc, declared at the virtual annual congress of the European Society of Cardiology.

He presented the 12-month results of RATE-AF (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), in which 160 seniors (mean age, 76 years) with moderate or severe symptoms caused by permanent atrial fibrillation (AFib) as well as heart failure symptoms were randomized to low-dose digoxin or the beta-blocker bisoprolol for rate control.

The open-label trial was designed to address a centuries-old unmet need: “Although digoxin has been in use since 1785, we have no longer-term clinical trials of digoxin in patients with AFib or AFib with heart failure,” noted Dr. Kotecha, professor of cardiology at the University of Birmingham (England).

Not only is digoxin greatly understudied in AFib, but permanent AFib – the most common form of the arrhythmia – has received only a tiny fraction of the research attention that’s been devoted to paroxysmal or persistent AFib, he added.

In RATE-AF, digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to the mid-70s at 6 and 12 months. Notably, only a handful of study participants required an additional rate control drug during the 12-month study. Nor did the two drugs differ in terms of their impact on patient-reported quality of life at 6 months as reflected by their Short Form–36 physical component score, the primary study endpoint. And both drugs were well tolerated, with 96% of patients in the digoxin group still on the drug at a mean of 161 mcg/day at 6 months, and 89% still on their beta-blocker.

But that’s pretty much where the similarities in outcomes ended.

For example, at 12 months, the digoxin group scored significantly higher than the beta-blocker group on several domains of the Short Form–36 physical component score, including vitality, physical function, and global health. More than half of the digoxin group had a two-class improvement in modified European Heart Rhythm Association AFib-related symptoms at 6 months, compared with 10% of the beta-blocker group. At 12 months, nearly 70% of the digoxin group had a two-class improvement, as did 30% on bisoprolol.

Heart failure symptoms in the digoxin group improved from a mean baseline New York Heart Association class of 2.4 to 1.5 at both 6 and 12 months; the improvement was more modest in the beta-blocker group, going from NYHA 2.4 at baseline to 2.0 at both 6 and 12 months. And while N-terminal of the prohormone brain natriuretic peptide levels improved in the digoxin group from a baseline of 1,095 pg/mL to 1,058 at 6 months and 960 at 12 months, NT-proBNP actually went up in the beta-blocker group, from 1,041 to 1,209-1,250 pg/mL at 12 months.

Moreover, Dr. Kotecha continued, while RATE-AF was underpowered to assess clinical events, it’s nevertheless noteworthy that a total of 29 adverse events occurred in 12 months in the digoxin group, compared with 142 with beta-blocker therapy. There were 12 unplanned hospital admissions in the digoxin group and 28 in the beta-blocker group, and 22 primary care visits for either AFib or cardiovascular symptoms in patients on digoxin versus 64 in the beta-blocker group.

“Our results suggest a wider use of digoxin for stable patients with permanent AFib,” Dr. Kotecha concluded. However, in an interview, Jonathan Piccini, MD, had a different take on the study results.

“I don’t think this study should widely impact clinical practice in the U.S.,” according to Dr. Piccini, director of cardiac electrophysiology at Duke University, Durham, N.C.

His reservations included RATE-AF’s modest sample size as well as uncertainty as to the trial’s generalizability, given that bisoprolol isn’t much used in the United States. Also, these were elderly patients with shortness of breath, and it’s unclear how effective digoxin would be for rate control in patients with permanent AFib who are more active.

“The classic teaching is that digoxin is great for rate control at rest, but when people are active it’s not nearly as good as beta-blockers or calcium-channel blockers,” the cardiologist said.

“A beta-blocker is still going to be my first-line rate control agent. But the results of RATE-AF do open my mind that for an older sedentary patient I may very well think twice now about using digoxin, because in that situation it looks like it achieves similar goals as a beta-blocker,” Dr. Piccini added.

On the plus side for RATE-AF: “I am very pleased to see that we have a randomized controlled trial focused on rate control in permanent AFib. It also tickles me pink to see a randomized, controlled study of digoxin. And I’m really excited to see a clinical trial that focuses on quality of life. It should give some confidence to know that from a quality of life perspective clinicians can consider using either digoxin or a beta-blocker for rate control,” he said.

American College of Cardiology vice president Dipti Itchhaporia, MD, said she’d need to see a much larger randomized trial including a calcium-channel blocker as a third-rate control arm before she’d consider digoxin as first-line rate control therapy in patients with AFib with or without heart failure. Also, she has reservations about drawing definitive conclusions from an open, unblinded study in which patient-reported outcomes are the primary endpoint.

“I think these were surprising findings given what we all think about digoxin in this country. In general, digoxin fell out of favor for rate control, mainly because of observational studies showing increased mortality. So most of us choose a beta-blocker,” she observed in an interview.

But of course, a randomized trial, even a 160-patient randomized trial, constitutes a higher level of evidence.

“I don’t think I’m going to convert tomorrow and make digoxin my first-line rate control therapy without more data. But RATE-AF does makes me stop and think about using it more than I did before in some of my permanent AFib patients,” said Dr. Itchhaporia, director of disease management at Hoag Memorial Hospital in Newport Beach, Calif.

Dr. Kotecha reported having no financial conflicts regarding the study, which was funded by the U.K. National Institute for Health Research, the British Heart Foundation, and the European Union.

[email protected]

Digoxin now deserves to be considered first-line therapy for long-term heart rate control in older patients with permanent atrial fibrillation and symptoms of heart failure, Dipak Kotecha, MBChB, PhD, MSc, declared at the virtual annual congress of the European Society of Cardiology.

He presented the 12-month results of RATE-AF (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), in which 160 seniors (mean age, 76 years) with moderate or severe symptoms caused by permanent atrial fibrillation (AFib) as well as heart failure symptoms were randomized to low-dose digoxin or the beta-blocker bisoprolol for rate control.

The open-label trial was designed to address a centuries-old unmet need: “Although digoxin has been in use since 1785, we have no longer-term clinical trials of digoxin in patients with AFib or AFib with heart failure,” noted Dr. Kotecha, professor of cardiology at the University of Birmingham (England).

Not only is digoxin greatly understudied in AFib, but permanent AFib – the most common form of the arrhythmia – has received only a tiny fraction of the research attention that’s been devoted to paroxysmal or persistent AFib, he added.

In RATE-AF, digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to the mid-70s at 6 and 12 months. Notably, only a handful of study participants required an additional rate control drug during the 12-month study. Nor did the two drugs differ in terms of their impact on patient-reported quality of life at 6 months as reflected by their Short Form–36 physical component score, the primary study endpoint. And both drugs were well tolerated, with 96% of patients in the digoxin group still on the drug at a mean of 161 mcg/day at 6 months, and 89% still on their beta-blocker.

But that’s pretty much where the similarities in outcomes ended.

For example, at 12 months, the digoxin group scored significantly higher than the beta-blocker group on several domains of the Short Form–36 physical component score, including vitality, physical function, and global health. More than half of the digoxin group had a two-class improvement in modified European Heart Rhythm Association AFib-related symptoms at 6 months, compared with 10% of the beta-blocker group. At 12 months, nearly 70% of the digoxin group had a two-class improvement, as did 30% on bisoprolol.

Heart failure symptoms in the digoxin group improved from a mean baseline New York Heart Association class of 2.4 to 1.5 at both 6 and 12 months; the improvement was more modest in the beta-blocker group, going from NYHA 2.4 at baseline to 2.0 at both 6 and 12 months. And while N-terminal of the prohormone brain natriuretic peptide levels improved in the digoxin group from a baseline of 1,095 pg/mL to 1,058 at 6 months and 960 at 12 months, NT-proBNP actually went up in the beta-blocker group, from 1,041 to 1,209-1,250 pg/mL at 12 months.

Moreover, Dr. Kotecha continued, while RATE-AF was underpowered to assess clinical events, it’s nevertheless noteworthy that a total of 29 adverse events occurred in 12 months in the digoxin group, compared with 142 with beta-blocker therapy. There were 12 unplanned hospital admissions in the digoxin group and 28 in the beta-blocker group, and 22 primary care visits for either AFib or cardiovascular symptoms in patients on digoxin versus 64 in the beta-blocker group.

“Our results suggest a wider use of digoxin for stable patients with permanent AFib,” Dr. Kotecha concluded. However, in an interview, Jonathan Piccini, MD, had a different take on the study results.

“I don’t think this study should widely impact clinical practice in the U.S.,” according to Dr. Piccini, director of cardiac electrophysiology at Duke University, Durham, N.C.

His reservations included RATE-AF’s modest sample size as well as uncertainty as to the trial’s generalizability, given that bisoprolol isn’t much used in the United States. Also, these were elderly patients with shortness of breath, and it’s unclear how effective digoxin would be for rate control in patients with permanent AFib who are more active.

“The classic teaching is that digoxin is great for rate control at rest, but when people are active it’s not nearly as good as beta-blockers or calcium-channel blockers,” the cardiologist said.

“A beta-blocker is still going to be my first-line rate control agent. But the results of RATE-AF do open my mind that for an older sedentary patient I may very well think twice now about using digoxin, because in that situation it looks like it achieves similar goals as a beta-blocker,” Dr. Piccini added.

On the plus side for RATE-AF: “I am very pleased to see that we have a randomized controlled trial focused on rate control in permanent AFib. It also tickles me pink to see a randomized, controlled study of digoxin. And I’m really excited to see a clinical trial that focuses on quality of life. It should give some confidence to know that from a quality of life perspective clinicians can consider using either digoxin or a beta-blocker for rate control,” he said.

American College of Cardiology vice president Dipti Itchhaporia, MD, said she’d need to see a much larger randomized trial including a calcium-channel blocker as a third-rate control arm before she’d consider digoxin as first-line rate control therapy in patients with AFib with or without heart failure. Also, she has reservations about drawing definitive conclusions from an open, unblinded study in which patient-reported outcomes are the primary endpoint.

“I think these were surprising findings given what we all think about digoxin in this country. In general, digoxin fell out of favor for rate control, mainly because of observational studies showing increased mortality. So most of us choose a beta-blocker,” she observed in an interview.

But of course, a randomized trial, even a 160-patient randomized trial, constitutes a higher level of evidence.

“I don’t think I’m going to convert tomorrow and make digoxin my first-line rate control therapy without more data. But RATE-AF does makes me stop and think about using it more than I did before in some of my permanent AFib patients,” said Dr. Itchhaporia, director of disease management at Hoag Memorial Hospital in Newport Beach, Calif.

Dr. Kotecha reported having no financial conflicts regarding the study, which was funded by the U.K. National Institute for Health Research, the British Heart Foundation, and the European Union.

[email protected]

Digoxin now deserves to be considered first-line therapy for long-term heart rate control in older patients with permanent atrial fibrillation and symptoms of heart failure, Dipak Kotecha, MBChB, PhD, MSc, declared at the virtual annual congress of the European Society of Cardiology.

He presented the 12-month results of RATE-AF (Rate Control Therapy Evaluation in Permanent Atrial Fibrillation), in which 160 seniors (mean age, 76 years) with moderate or severe symptoms caused by permanent atrial fibrillation (AFib) as well as heart failure symptoms were randomized to low-dose digoxin or the beta-blocker bisoprolol for rate control.

The open-label trial was designed to address a centuries-old unmet need: “Although digoxin has been in use since 1785, we have no longer-term clinical trials of digoxin in patients with AFib or AFib with heart failure,” noted Dr. Kotecha, professor of cardiology at the University of Birmingham (England).

Not only is digoxin greatly understudied in AFib, but permanent AFib – the most common form of the arrhythmia – has received only a tiny fraction of the research attention that’s been devoted to paroxysmal or persistent AFib, he added.

In RATE-AF, digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to the mid-70s at 6 and 12 months. Notably, only a handful of study participants required an additional rate control drug during the 12-month study. Nor did the two drugs differ in terms of their impact on patient-reported quality of life at 6 months as reflected by their Short Form–36 physical component score, the primary study endpoint. And both drugs were well tolerated, with 96% of patients in the digoxin group still on the drug at a mean of 161 mcg/day at 6 months, and 89% still on their beta-blocker.

But that’s pretty much where the similarities in outcomes ended.

For example, at 12 months, the digoxin group scored significantly higher than the beta-blocker group on several domains of the Short Form–36 physical component score, including vitality, physical function, and global health. More than half of the digoxin group had a two-class improvement in modified European Heart Rhythm Association AFib-related symptoms at 6 months, compared with 10% of the beta-blocker group. At 12 months, nearly 70% of the digoxin group had a two-class improvement, as did 30% on bisoprolol.

Heart failure symptoms in the digoxin group improved from a mean baseline New York Heart Association class of 2.4 to 1.5 at both 6 and 12 months; the improvement was more modest in the beta-blocker group, going from NYHA 2.4 at baseline to 2.0 at both 6 and 12 months. And while N-terminal of the prohormone brain natriuretic peptide levels improved in the digoxin group from a baseline of 1,095 pg/mL to 1,058 at 6 months and 960 at 12 months, NT-proBNP actually went up in the beta-blocker group, from 1,041 to 1,209-1,250 pg/mL at 12 months.

Moreover, Dr. Kotecha continued, while RATE-AF was underpowered to assess clinical events, it’s nevertheless noteworthy that a total of 29 adverse events occurred in 12 months in the digoxin group, compared with 142 with beta-blocker therapy. There were 12 unplanned hospital admissions in the digoxin group and 28 in the beta-blocker group, and 22 primary care visits for either AFib or cardiovascular symptoms in patients on digoxin versus 64 in the beta-blocker group.

“Our results suggest a wider use of digoxin for stable patients with permanent AFib,” Dr. Kotecha concluded. However, in an interview, Jonathan Piccini, MD, had a different take on the study results.

“I don’t think this study should widely impact clinical practice in the U.S.,” according to Dr. Piccini, director of cardiac electrophysiology at Duke University, Durham, N.C.

His reservations included RATE-AF’s modest sample size as well as uncertainty as to the trial’s generalizability, given that bisoprolol isn’t much used in the United States. Also, these were elderly patients with shortness of breath, and it’s unclear how effective digoxin would be for rate control in patients with permanent AFib who are more active.

“The classic teaching is that digoxin is great for rate control at rest, but when people are active it’s not nearly as good as beta-blockers or calcium-channel blockers,” the cardiologist said.

“A beta-blocker is still going to be my first-line rate control agent. But the results of RATE-AF do open my mind that for an older sedentary patient I may very well think twice now about using digoxin, because in that situation it looks like it achieves similar goals as a beta-blocker,” Dr. Piccini added.

On the plus side for RATE-AF: “I am very pleased to see that we have a randomized controlled trial focused on rate control in permanent AFib. It also tickles me pink to see a randomized, controlled study of digoxin. And I’m really excited to see a clinical trial that focuses on quality of life. It should give some confidence to know that from a quality of life perspective clinicians can consider using either digoxin or a beta-blocker for rate control,” he said.

American College of Cardiology vice president Dipti Itchhaporia, MD, said she’d need to see a much larger randomized trial including a calcium-channel blocker as a third-rate control arm before she’d consider digoxin as first-line rate control therapy in patients with AFib with or without heart failure. Also, she has reservations about drawing definitive conclusions from an open, unblinded study in which patient-reported outcomes are the primary endpoint.

“I think these were surprising findings given what we all think about digoxin in this country. In general, digoxin fell out of favor for rate control, mainly because of observational studies showing increased mortality. So most of us choose a beta-blocker,” she observed in an interview.

But of course, a randomized trial, even a 160-patient randomized trial, constitutes a higher level of evidence.

“I don’t think I’m going to convert tomorrow and make digoxin my first-line rate control therapy without more data. But RATE-AF does makes me stop and think about using it more than I did before in some of my permanent AFib patients,” said Dr. Itchhaporia, director of disease management at Hoag Memorial Hospital in Newport Beach, Calif.

Dr. Kotecha reported having no financial conflicts regarding the study, which was funded by the U.K. National Institute for Health Research, the British Heart Foundation, and the European Union.

[email protected]