Cardiology News

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Saxenda, Novo Nordisk) was safe and effective for treating weight regain after Roux-en-Y gastric bypass (RYGB), in a randomized controlled trial.

That is, 132 patients who had lost at least 25% of their initial weight after RYGB and then gained at least 10% back were randomized 2:1 to receive liraglutide plus frequent lifestyle advice from a registered dietitian or lifestyle advice alone.

After a year, 69%, 48%, and 24% of patients who had received liraglutide lost at least 5%, 10%, and 15% of their study entry weight, respectively. In contrast, only 5% of patients in the control group lost at least 5% of their weight and none lost at least 10% of their weight.

“Liraglutide 3.0 mg/day, with lifestyle modification, was significantly more effective than placebo in treating weight regain after RYGB without increased risk of serious adverse events,” Holly F. Lofton, MD, summarized this week in an oral session at ObesityWeek®, the annual meeting of The Obesity Society.

Dr. Lofton, a clinical associate professor of surgery and medicine, and director, weight management program, NYU, Langone Health, explained to this news organization that she initiated the study after attending a “packed” session about post bariatric surgery weight regain at a prior American Society of Metabolic and Bariatric Surgery conference.

“The lecturers recommended conservative measures (such as reiterating the diet recommendations, exercise, [and] counseling), and revisional surgeries,” she said in an email, but at the time “there was no literature that provided direction on which pharmacotherapies are best for this population.”

It was known that decreases in endogenous GLP-1 levels coincide with weight regain, and liraglutide (Saxenda) was the only GLP-1 agonist approved for chronic weight management at the time, so she devised the current study protocol.

The findings are especially helpful for patients who are not candidates for bariatric surgery revisions, she noted. Further research is needed to investigate the effect of newer GLP-1 agonists, such as semaglutide (Wegovy), on weight regain following different types of bariatric surgery.

Asked to comment, Wendy C. King, PhD, who was not involved with this research, said that more than two-thirds of patients treated with 3 mg/day subcutaneous liraglutide injections in the current study lost at least 5% of their initial weight a year later, and 20% of them attained a weight as low as, or lower than, their lowest weight after bariatric surgery (nadir weight).

“The fact that both groups received lifestyle counseling from registered dietitians for just over a year, but only patients in the liraglutide group lost weight, on average, speaks to the difficulty of losing weight following weight regain post–bariatric surgery,” added Dr. King, an associate professor of epidemiology at the University of Pittsburgh, Pennsylvania.

This study “provides data that may help clinicians and patients understand the potential effect of adding liraglutide 3.0 mg/day to their weight loss efforts,” she told this news organization in an email.

However, “given that 42% of those on liraglutide reported gastrointestinal-related side effects, patients should also be counseled on this potential outcome and given suggestions for how to minimize such side effects,” Dr. King suggested.
 

Weight regain common, repeat surgery entails risk

Weight regain is common even years after bariatric surgery. Repeat surgery entails some risk, and lifestyle approaches alone are rarely successful in reversing weight regain, Dr. Lofton told the audience.

The researchers enrolled 132 adults who had a mean weight of 134 kg (295 pounds) when they underwent RYGB, and who lost at least 25% of their initial weight (mean weight loss of 38%) after the surgery, but who also regained at least 10% of their initial weight.

At enrollment of the current study (baseline), the patients had had RYGB 18 months to 10 years earlier (mean 5.7 years earlier) and now had a mean weight of 99 kg (218 pounds) and a mean BMI of 35.6 kg/m². None of the patients had diabetes.  

The patients were randomized to receive liraglutide (n = 89, 84% women) or placebo (n = 43, 88% women) for 56 weeks.

They were a mean age of 48 years, and about 59% were White and 25% were Black.

All patients had clinic visits every 3 months where they received lifestyle counseling from a registered dietitian.

At 12 months, patients in the liraglutide group had lost a mean of 8.8% of their baseline weight, whereas those in the placebo group had gained a mean of 1.48% of their baseline weight.

There were no significant between-group differences in cardiometabolic variables.

None of the patients in the control group attained a weight that was as low as their nadir weight after RYGB.

The rates of nausea (25%), constipation (16%), and abdominal pain (10%) in the liraglutide group were higher than in the placebo group (7%, 14%, and 5%, respectively) but similar to rates of gastrointestinal side effects in other trials of this agent.

Dr. Lofton has disclosed receiving consulting fees and being on a speaker bureau for Novo Nordisk and receiving research funds from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Dr. King has reported no relevant financial relationships.

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

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

The use of statins by patients with rheumatoid arthritis appears to provide an overall net benefit on cardiovascular disease outcomes that outweighs the risk of type 2 diabetes mellitus (T2DM) seen with the drugs in the general population, according to evidence from a cohort study of more than 16,000 people in the United Kingdom that was presented at the virtual annual meeting of the American College of Rheumatology.

“Our study emphasizes that RA patients should be assessed for statin initiation to improve CVD risk,” lead study author Gulsen Ozen, MD, a third-year resident at the University of Nebraska, Omaha, said in an interview. Because the risk of T2DM with statin use is no worse in patients with RA than in the general population, statin initiation “is actually a great opportunity to address the risk factors for T2DM such as activity and exercise, obesity and weight loss, and [use of glucocorticoids], which have other important health effects,” she said.

“Also, importantly, even if [patients] develop T2DM, statins still work on CVD and mortality outcomes as in patients without diabetes,” Dr. Ozen added. “Given all, the benefits of statins way outweigh the hazards.”

Dr. Ozen said this was the first large cohort study to evaluate CVD mortality and T2DM risks with statins in patients with RA, a claim with which rheumatologist Elena Myasoedova, MD, PhD, of the Mayo Clinic in Rochester, Minn., concurred.

Dr. Myasoedova, professor of rheumatology and epidemiology at Mayo, said in an interview that the study was “methodologically rigorous” using time-conditional propensity score (TCPS) matching and a prevalent new-user design, “thus addressing the immortal time bias” found in the design of studies in which patients enter a cohort but do not start a treatment before developing the outcome of interest and are assigned to the untreated group or when the period of delay from when patients enter the cohort to when they are treated is excluded from the analysis. An earlier study from the same authors did not use TCPS matching, she said.

“The study findings suggest that patients with RA can benefit from statin use in terms of CVD outcomes and mortality but physicians should use vigilance regarding increased T2DM risk and discuss this possibility with patients,” Dr. Myasoedova said. “Identifying patients who are at higher risk of developing T2DM after statin initiation would be important to personalize the approach to statin therapy.”
 

Study details

The study accessed records from the U.K. Clinical Practice Research Datalink and linked Hospital Episode Statistics and Office of National Statistics databases. It analyzed adult patients with RA who were diagnosed during 1989-2018 in two cohorts: One for CVD and all-cause mortality, consisting of 1,768 statin initiators and 3,528 TCPS-matched nonusers; and a T2DM cohort with 3,608 statin initiators and 7,208 TCPS-matched nonusers.

In the entire cohort, statin use was associated with a 32% reduction in CV events (composite endpoint of the nonfatal or fatal MI, stroke, hospitalized heart failure, or CVD mortality), a 54% reduction in all-cause mortality, and a 33% increase in risk for T2DM, Dr. Ozen said. Results were similar in both sexes, although CV event reduction with statins in men did not reach statistical significance, likely because of a smaller sample size, she said.

Patients with and without a history of CVD had a similar reduction in CV events and all-cause mortality, and risk for T2DM increased with statins, but the latter reached statistical significance only in patients without a history of CVD, Dr. Ozen said.

Patients with RA who are at risk for T2DM and who are taking statins require blood glucose monitoring, which is typically done in patients with RA on disease-modifying antirheumatic drugs, and hemoglobin A1c testing when glucose levels are impaired, she said. “Any concerns for T2DM would be also communicated by the primary care providers of the patients to initiate further assessment and management,” she said.

But Dr. Ozen noted that confusion exists among primary care physicians and rheumatologists about who’s responsible for prescribing statins in these patients. “I would like to remind you that instead of assigning this role to a certain specialty, just good communication could improve this care gap of statin underutilization in RA,” she said. “Also, for rheumatologists, given that all-cause mortality reduction with statins was as high as CV event reduction, statins may be reducing other causes of mortality through improving disease activity.”

Bristol-Myers Squibb provided funding for the study. Dr. Ozen and Dr. Myasoedova have no relevant disclosures.

Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.

In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.

MASTER DAPT main results published

The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.

In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.

Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).

When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.

Recent MI vs. no MI

In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.

In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).

For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.

“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
 

No difference in NACE components

In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.

There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).

As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).

In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.

According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.

“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.

Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.

Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.

In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.

MASTER DAPT main results published

The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.

In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.

Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).

When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.

Recent MI vs. no MI

In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.

In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).

For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.

“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
 

No difference in NACE components

In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.

There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).

As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).

In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.

According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.

“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.

Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.

Just months after the MASTER DAPT trial showed that abbreviated dual-antiplatelet therapy (DAPT) lowers the risk of bleeding after stent placement in patients at high bleeding risk, a new analysis showed the favorable benefit-to-risk ratio was about the same in the subgroup who also had an acute or recent myocardial infarction.

In the new prespecified MASTER DAPT analysis, the data show that the subgroup with both an increased bleeding risk and an increased risk of ischemic events benefited much like the entire study population from a shorter DAPT duration, reported Pieter C. Smits, MD, PhD, at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

“There was no signal towards increased ischemic risk in the abbreviated DAPT population presenting with recent acute MI,” said Dr. Smits, emphasizing the consistency of results in this “bi-risk” subgroup with objective criteria for increased risks of bleeding and ischemic events.

MASTER DAPT main results published

The main results of the MASTER DAPT trial were presented at the 2021 annual meeting of the European Society of Cardiology and published recently in the New England Journal of Medicine. The trial randomized 4,434 patients who met one or more criteria for high bleeding risk. These included age of at least 75 years, documented anemia, a clinical indication for oral anticoagulants, and previous bleeding episodes requiring hospitalization.

In the trial, all patients were maintained on DAPT for 1 month after implantation of a biodegradable-polymer, sirolimus-eluting coronary stent (Ultimaster, Terumo). At the end of the month, those randomized to abbreviated DAPT started immediately on single-agent antiplatelet therapy, while those in the standard DAPT group remained on DAPT for at least 2 additional months.

Over 1 year of follow-up, the bleeding event rate was lower in the abbreviated DAPT group (6.5% vs. 9.4%; P < .0001 for superiority). The slight increase in major ischemic events among those in the abbreviated DAPT group (6.1% vs. 5.9%) was not significantly different (P = .001 for noninferiority).

When compared on the basis of net adverse clinical events (NACE), which comprised all-case death, MI, stroke, or Bleeding Academic Research Consortium (BARC) level 3 or 5 bleeding, there was a slight advantage for abbreviated DAPT (7.5% vs. 7.7%). This did not reach significance, but it was similar (P < .001 for noninferiority), favoring the abbreviated course of DAPT because of the bleeding advantage.

Recent MI vs. no MI

In the new analysis, patients in both the abbreviated and standard DAPT group were stratified into those with no major cardiovascular event within the past 12 months and those with an acute MI or acute coronary syndrome within this time. There were somewhat more patients without a history of MI within the previous 12 months in both the abbreviated DAPT (1,381 vs. 914 patients) and standard DAPT (1,418 vs. 866) groups.

In those without a recent MI, NACE rates were nearly identical over 1-year follow-up for those who received abbreviated versus standard DAPT. In both, slightly more than 6% had a NACE event, producing a hazard ratio of 1.03 for abbreviated versus standard DAPT (P = 0.85).

For those with a recent MI, event rates began to separate within 30 days. By 1 year, NACE rates exceeded 10% in those on standard DAPT, but remained below 9% for those on abbreviated DAPT. The lower hazard ratio in the abbreviated DAPT group (HR, 0.83; P = .22) did not reach statistical significance, but it did echo the larger MASTER DAPT conclusion.

“An abbreviated DAPT strategy significantly reduced clinically relevant bleeding risk in these bi-risk patients without increasing risk of ischemic events,” reported Dr. Smits, director of interventional cardiology at Maasstad Hospital, Rotterdam, the Netherlands.
 

No difference in NACE components

In fact, when the components of NACE were evaluated individually in the subgroup of patients with prior MI, both stroke (HR, 0.47; P = .16) and all-cause death (HR, 0.78; P = .28), although not significant, numerically favored abbreviated DAPT.

There was no difference between abbreviated and standard DAPT for risk of MI at 1 year (HR, 1.03; P = .92).

As in the overall MASTER DAPT results, bleeding risk (BARC 2, 3, or 5 bleeding) was significantly reduced in the substudy among those with a recent prior MI (P = .013) or those with no MI in the prior 12 months (P = .01).

In MASTER DAPT, which was an open-label study that randomized participants in 30 countries, all patients received one type of drug-eluting stent. While Dr. Smits conceded that it is not clear whether the conclusions about abbreviated DAPT can be extrapolated to other stents, he noted that recent long-term outcomes for modern drug-eluting coronary stents have been similar, suggesting these results might be more broadly applicable.

According to Dr. Smit, the consistency of this subgroup analysis with the previously published MASTER DAPT study is mutually reinforcing for a role of abbreviated DAPT in patients at high bleeding risk. Other experts agreed.

“One of the concerns that people have had is exactly what has been addressed here in this subgroup analysis. These are the patients that are not only bleeding-risk high but ischemic-risk high. The question was whether the benefit of reducing bleeding risk is offset by increasing stent thrombosis or other ischemic event outcomes, and the answer from the analysis is really clearly no,” said Philippe Gabriel Steg, MD, chief, department of cardiology, Hôpital Bichat, Paris, at the meeting, sponsored by the Cardiovascular Research Foundation.

Dr. Smits reports financial relationships with Abiomed, Abbott Vascular, Daiichi-Sankyo, Microport, Opsense, and Terumo Medical. Dr. Steg reports financial relationships with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Idorsia, Merck, Novartis, Regeneron, and Sanofi-Aventis.

“When considering the challenges of obesity, ask yourself: ‘If it were diabetes, cancer, HIV, or Alzheimer’s, how would you discuss it, approach it, assess it, treat it?’” Lee M. Kaplan, MD, PhD, asked the audience of health care professionals during ObesityWeek®, the annual meeting of The Obesity Society.

“And then do it for obesity, using the full spectrum of tools at our disposal,” he advised.

This was the takeaway that Dr. Kaplan, director of the Obesity, Metabolism, and Nutrition Institute at Massachusetts General Hospital and associate professor, Harvard Medical School, Boston, left the audience with at the end of his lecture entitled, “What does the future of obesity care look like?”

Invited to summarize his main points, Dr. Kaplan told this news organization in an interview that practitioners caring for patients with obesity need to first “recognize that obesity is a disease” caused by dysfunction of the metabolic system that regulates body fat – in the same way immune dysregulation can lead to asthma.

Second, “we are finally developing noninvasive therapies that are more effective,” he noted, referring to the recently approved semaglutide, and even more potent weight-loss therapies that could be on the market within 3 years, so that weight-loss outcomes with pharmacotherapy are approaching those with bariatric surgery.

Third, it is important that patients with obesity get “broad and equitable access” to treatment, and health care practitioners need to be on the same page and have a “shared understanding” of which treatments are appropriate for individual patients, “just as we do for other diseases.”  
 

Need for a shared understanding

“Dr. Kaplan really brought home the idea that we all need a shared understanding of what obesity is – and what it is not,” agreed symposium moderator Donna H. Ryan, MD, in an email.

“He underscored the biologic basis of obesity,” noted Dr. Ryan, professor emerita at Pennington Biomedical Research Center in Baton Rouge, Louisiana, and associate editor-in-chief of Obesity, the official journal of The Obesity Society.

“It is a dysregulation of the body’s weight (especially adipose tissue) regulatory system,” she continued. “The body responds to powerful environmental pressures that produce excess energy balance, and we store that as fat and defend our highest fat mass. This makes obesity a disease, a chronic disease that requires a medical approach to reverse. It’s not a cosmetic problem, it’s a medical problem,” she emphasized.

There is so much misinformation out there about obesity, according to Dr. Ryan.

“People think it’s a lack of willpower, and even patients blame themselves for not being able to lose weight and keep it off. It’s not their fault! It’s biology.”

Although the supplement industry and fad diets falsely promise fast results, there is no magic diet, she continued.

“But we have made progress based on understanding the biologic basis of obesity and have new medications that offer real hope for patients.” 

“With 42% of U.S. adults having a BMI that qualifies as obesity, we need a concerted and broad effort to address this problem, and that starts with everybody on the same page as to what obesity is ... a shared understanding of the biologic basis of obesity. It’s time to take obesity seriously,” she summarized, echoing Dr. Kaplan.
 

A question of biology

“Obesity results from inappropriate pathophysiological regulation of body fat mass,” when the body defends adiposity, Dr. Kaplan explained at the start of his lecture.

The treatment strategy for obesity has always been a stepwise approach starting with lifestyle changes, then pharmacotherapy, then possibly bariatric surgery – each step with a potentially greater chance of weight loss. But now, he explained, medicine is on the verge of having an armamentarium of more potent weight-loss medications.

Compared with phentermine/topiramate, orlistat, naltrexone/bupropion, and liraglutide – which roughly might provide 5% to 10% weight loss, the glucagon-like peptide-1 (GLP-1) agonist semaglutide 2.4 mg/week (Wegovy, Novo Nordisk), approved by the U.S. Food and Drug Association in June, provides almost double this potential weight loss.

And two new agents that could provide “never seen before weight loss” of 25% could potentially enter the marketplace by 2025: the amylin agonist cagrilintide (Novo Nordisk) and the twincretin tirzepatide (Eli Lilly) (a combined glucose-dependent insulinotropic polypeptide [GIP] and GLP-1 receptor agonist).

In addition, when liraglutide comes off patent, a generic version could potentially be introduced, and combined generic liraglutide plus generic phentermine/topiramate could be a less expensive weight-loss treatment option in the future, he noted.
 

One size does not fit all

Importantly, weight loss varies widely among individual patients.

A graph of potential weight loss with different treatments (for example, bariatric surgery or liraglutide) versus the percentage of patients that attain the weight losses is roughly bell-shaped, Dr. Kaplan explained. For example, in the STEP1 trial of semaglutide, roughly 7.1% of patients lost less than 5% of their initial weight, 25% of patients lost 20% to 30%, and 10.8% of patients lost 30% or more; that is, patients at the higher end had weight loss comparable to that seen with bariatric surgery

Adding pharmacotherapy after bariatric surgery could be synergistic. For example, in the GRAVITAS study of patients with type 2 diabetes who had gastric bypass surgery, those who received liraglutide after surgery had augmented weight loss compared with those who received placebo.

People at a cocktail party might come up to him and say, “I’d like to lose 5 pounds, 10 pounds,” Dr. Kaplan related in the Q&A session.

“That’s not obesity,” he emphasized. Obesity is excess body fat that poses a risk to health. A person with obesity may have 50 or more excess pounds, and the body is trying to defend this weight.

“If we want to treat obesity more effectively, we have to fully understand why it is a disease and how that disease differs from the cultural desire for thinness,” he reiterated.

“We have to keep the needs and goals of all people living with obesity foremost in our minds, even if many of them have been previously misled by the bias, stigma, blame, and discrimination that surrounds them.”

“We need to re-evaluate what we think we know about obesity and open our minds to new ideas,” he added.

Dr. Kaplan has reported financial ties to Eli Lilly, Gelesis, GI Dynamics, IntelliHealth, Johnson & Johnson, Novo Nordisk, Pfizer, and Rhythm Pharmaceuticals. Dr. Ryan has ties to numerous Novo Nordisk, Pfizer, and several other pharmaceutical companies, including having an ownership interest in Gila Therapeutics, Xeno Biosciences, Epitomee, Calibrate, Roman, and Scientific Intake.

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

“When considering the challenges of obesity, ask yourself: ‘If it were diabetes, cancer, HIV, or Alzheimer’s, how would you discuss it, approach it, assess it, treat it?’” Lee M. Kaplan, MD, PhD, asked the audience of health care professionals during ObesityWeek®, the annual meeting of The Obesity Society.

“And then do it for obesity, using the full spectrum of tools at our disposal,” he advised.

This was the takeaway that Dr. Kaplan, director of the Obesity, Metabolism, and Nutrition Institute at Massachusetts General Hospital and associate professor, Harvard Medical School, Boston, left the audience with at the end of his lecture entitled, “What does the future of obesity care look like?”

Invited to summarize his main points, Dr. Kaplan told this news organization in an interview that practitioners caring for patients with obesity need to first “recognize that obesity is a disease” caused by dysfunction of the metabolic system that regulates body fat – in the same way immune dysregulation can lead to asthma.

Second, “we are finally developing noninvasive therapies that are more effective,” he noted, referring to the recently approved semaglutide, and even more potent weight-loss therapies that could be on the market within 3 years, so that weight-loss outcomes with pharmacotherapy are approaching those with bariatric surgery.

Third, it is important that patients with obesity get “broad and equitable access” to treatment, and health care practitioners need to be on the same page and have a “shared understanding” of which treatments are appropriate for individual patients, “just as we do for other diseases.”  
 

Need for a shared understanding

“Dr. Kaplan really brought home the idea that we all need a shared understanding of what obesity is – and what it is not,” agreed symposium moderator Donna H. Ryan, MD, in an email.

“He underscored the biologic basis of obesity,” noted Dr. Ryan, professor emerita at Pennington Biomedical Research Center in Baton Rouge, Louisiana, and associate editor-in-chief of Obesity, the official journal of The Obesity Society.

“It is a dysregulation of the body’s weight (especially adipose tissue) regulatory system,” she continued. “The body responds to powerful environmental pressures that produce excess energy balance, and we store that as fat and defend our highest fat mass. This makes obesity a disease, a chronic disease that requires a medical approach to reverse. It’s not a cosmetic problem, it’s a medical problem,” she emphasized.

There is so much misinformation out there about obesity, according to Dr. Ryan.

“People think it’s a lack of willpower, and even patients blame themselves for not being able to lose weight and keep it off. It’s not their fault! It’s biology.”

Although the supplement industry and fad diets falsely promise fast results, there is no magic diet, she continued.

“But we have made progress based on understanding the biologic basis of obesity and have new medications that offer real hope for patients.” 

“With 42% of U.S. adults having a BMI that qualifies as obesity, we need a concerted and broad effort to address this problem, and that starts with everybody on the same page as to what obesity is ... a shared understanding of the biologic basis of obesity. It’s time to take obesity seriously,” she summarized, echoing Dr. Kaplan.
 

A question of biology

“Obesity results from inappropriate pathophysiological regulation of body fat mass,” when the body defends adiposity, Dr. Kaplan explained at the start of his lecture.

The treatment strategy for obesity has always been a stepwise approach starting with lifestyle changes, then pharmacotherapy, then possibly bariatric surgery – each step with a potentially greater chance of weight loss. But now, he explained, medicine is on the verge of having an armamentarium of more potent weight-loss medications.

Compared with phentermine/topiramate, orlistat, naltrexone/bupropion, and liraglutide – which roughly might provide 5% to 10% weight loss, the glucagon-like peptide-1 (GLP-1) agonist semaglutide 2.4 mg/week (Wegovy, Novo Nordisk), approved by the U.S. Food and Drug Association in June, provides almost double this potential weight loss.

And two new agents that could provide “never seen before weight loss” of 25% could potentially enter the marketplace by 2025: the amylin agonist cagrilintide (Novo Nordisk) and the twincretin tirzepatide (Eli Lilly) (a combined glucose-dependent insulinotropic polypeptide [GIP] and GLP-1 receptor agonist).

In addition, when liraglutide comes off patent, a generic version could potentially be introduced, and combined generic liraglutide plus generic phentermine/topiramate could be a less expensive weight-loss treatment option in the future, he noted.
 

One size does not fit all

Importantly, weight loss varies widely among individual patients.

A graph of potential weight loss with different treatments (for example, bariatric surgery or liraglutide) versus the percentage of patients that attain the weight losses is roughly bell-shaped, Dr. Kaplan explained. For example, in the STEP1 trial of semaglutide, roughly 7.1% of patients lost less than 5% of their initial weight, 25% of patients lost 20% to 30%, and 10.8% of patients lost 30% or more; that is, patients at the higher end had weight loss comparable to that seen with bariatric surgery

Adding pharmacotherapy after bariatric surgery could be synergistic. For example, in the GRAVITAS study of patients with type 2 diabetes who had gastric bypass surgery, those who received liraglutide after surgery had augmented weight loss compared with those who received placebo.

People at a cocktail party might come up to him and say, “I’d like to lose 5 pounds, 10 pounds,” Dr. Kaplan related in the Q&A session.

“That’s not obesity,” he emphasized. Obesity is excess body fat that poses a risk to health. A person with obesity may have 50 or more excess pounds, and the body is trying to defend this weight.

“If we want to treat obesity more effectively, we have to fully understand why it is a disease and how that disease differs from the cultural desire for thinness,” he reiterated.

“We have to keep the needs and goals of all people living with obesity foremost in our minds, even if many of them have been previously misled by the bias, stigma, blame, and discrimination that surrounds them.”

“We need to re-evaluate what we think we know about obesity and open our minds to new ideas,” he added.

Dr. Kaplan has reported financial ties to Eli Lilly, Gelesis, GI Dynamics, IntelliHealth, Johnson & Johnson, Novo Nordisk, Pfizer, and Rhythm Pharmaceuticals. Dr. Ryan has ties to numerous Novo Nordisk, Pfizer, and several other pharmaceutical companies, including having an ownership interest in Gila Therapeutics, Xeno Biosciences, Epitomee, Calibrate, Roman, and Scientific Intake.

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

“When considering the challenges of obesity, ask yourself: ‘If it were diabetes, cancer, HIV, or Alzheimer’s, how would you discuss it, approach it, assess it, treat it?’” Lee M. Kaplan, MD, PhD, asked the audience of health care professionals during ObesityWeek®, the annual meeting of The Obesity Society.

“And then do it for obesity, using the full spectrum of tools at our disposal,” he advised.

This was the takeaway that Dr. Kaplan, director of the Obesity, Metabolism, and Nutrition Institute at Massachusetts General Hospital and associate professor, Harvard Medical School, Boston, left the audience with at the end of his lecture entitled, “What does the future of obesity care look like?”

Invited to summarize his main points, Dr. Kaplan told this news organization in an interview that practitioners caring for patients with obesity need to first “recognize that obesity is a disease” caused by dysfunction of the metabolic system that regulates body fat – in the same way immune dysregulation can lead to asthma.

Second, “we are finally developing noninvasive therapies that are more effective,” he noted, referring to the recently approved semaglutide, and even more potent weight-loss therapies that could be on the market within 3 years, so that weight-loss outcomes with pharmacotherapy are approaching those with bariatric surgery.

Third, it is important that patients with obesity get “broad and equitable access” to treatment, and health care practitioners need to be on the same page and have a “shared understanding” of which treatments are appropriate for individual patients, “just as we do for other diseases.”  
 

Need for a shared understanding

“Dr. Kaplan really brought home the idea that we all need a shared understanding of what obesity is – and what it is not,” agreed symposium moderator Donna H. Ryan, MD, in an email.

“He underscored the biologic basis of obesity,” noted Dr. Ryan, professor emerita at Pennington Biomedical Research Center in Baton Rouge, Louisiana, and associate editor-in-chief of Obesity, the official journal of The Obesity Society.

“It is a dysregulation of the body’s weight (especially adipose tissue) regulatory system,” she continued. “The body responds to powerful environmental pressures that produce excess energy balance, and we store that as fat and defend our highest fat mass. This makes obesity a disease, a chronic disease that requires a medical approach to reverse. It’s not a cosmetic problem, it’s a medical problem,” she emphasized.

There is so much misinformation out there about obesity, according to Dr. Ryan.

“People think it’s a lack of willpower, and even patients blame themselves for not being able to lose weight and keep it off. It’s not their fault! It’s biology.”

Although the supplement industry and fad diets falsely promise fast results, there is no magic diet, she continued.

“But we have made progress based on understanding the biologic basis of obesity and have new medications that offer real hope for patients.” 

“With 42% of U.S. adults having a BMI that qualifies as obesity, we need a concerted and broad effort to address this problem, and that starts with everybody on the same page as to what obesity is ... a shared understanding of the biologic basis of obesity. It’s time to take obesity seriously,” she summarized, echoing Dr. Kaplan.
 

A question of biology

“Obesity results from inappropriate pathophysiological regulation of body fat mass,” when the body defends adiposity, Dr. Kaplan explained at the start of his lecture.

The treatment strategy for obesity has always been a stepwise approach starting with lifestyle changes, then pharmacotherapy, then possibly bariatric surgery – each step with a potentially greater chance of weight loss. But now, he explained, medicine is on the verge of having an armamentarium of more potent weight-loss medications.

Compared with phentermine/topiramate, orlistat, naltrexone/bupropion, and liraglutide – which roughly might provide 5% to 10% weight loss, the glucagon-like peptide-1 (GLP-1) agonist semaglutide 2.4 mg/week (Wegovy, Novo Nordisk), approved by the U.S. Food and Drug Association in June, provides almost double this potential weight loss.

And two new agents that could provide “never seen before weight loss” of 25% could potentially enter the marketplace by 2025: the amylin agonist cagrilintide (Novo Nordisk) and the twincretin tirzepatide (Eli Lilly) (a combined glucose-dependent insulinotropic polypeptide [GIP] and GLP-1 receptor agonist).

In addition, when liraglutide comes off patent, a generic version could potentially be introduced, and combined generic liraglutide plus generic phentermine/topiramate could be a less expensive weight-loss treatment option in the future, he noted.
 

One size does not fit all

Importantly, weight loss varies widely among individual patients.

A graph of potential weight loss with different treatments (for example, bariatric surgery or liraglutide) versus the percentage of patients that attain the weight losses is roughly bell-shaped, Dr. Kaplan explained. For example, in the STEP1 trial of semaglutide, roughly 7.1% of patients lost less than 5% of their initial weight, 25% of patients lost 20% to 30%, and 10.8% of patients lost 30% or more; that is, patients at the higher end had weight loss comparable to that seen with bariatric surgery

Adding pharmacotherapy after bariatric surgery could be synergistic. For example, in the GRAVITAS study of patients with type 2 diabetes who had gastric bypass surgery, those who received liraglutide after surgery had augmented weight loss compared with those who received placebo.

People at a cocktail party might come up to him and say, “I’d like to lose 5 pounds, 10 pounds,” Dr. Kaplan related in the Q&A session.

“That’s not obesity,” he emphasized. Obesity is excess body fat that poses a risk to health. A person with obesity may have 50 or more excess pounds, and the body is trying to defend this weight.

“If we want to treat obesity more effectively, we have to fully understand why it is a disease and how that disease differs from the cultural desire for thinness,” he reiterated.

“We have to keep the needs and goals of all people living with obesity foremost in our minds, even if many of them have been previously misled by the bias, stigma, blame, and discrimination that surrounds them.”

“We need to re-evaluate what we think we know about obesity and open our minds to new ideas,” he added.

Dr. Kaplan has reported financial ties to Eli Lilly, Gelesis, GI Dynamics, IntelliHealth, Johnson & Johnson, Novo Nordisk, Pfizer, and Rhythm Pharmaceuticals. Dr. Ryan has ties to numerous Novo Nordisk, Pfizer, and several other pharmaceutical companies, including having an ownership interest in Gila Therapeutics, Xeno Biosciences, Epitomee, Calibrate, Roman, and Scientific Intake.

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

Percutaneous coronary intervention (PCI) guided by quantitative flow ratio (QFR) lesion assessment provided better clinical outcomes than visual assessment of the angiogram in the sham-controlled FAVOR III China study.

PCI success rates were about 95% with both strategies; however, QFR guidance was associated with fewer major adverse cardiac events (MACE) at 1 year, use of fewer stents, less contrast medium exposure, and fewer procedural complications.

“The simplicity and safety of QFR compared with wire-based physiologic measurements should facilitate the adoption of physiologic lesion assessment into routine clinical practice,” co–primary investigator Bo Xu, MBBS, Fuwai Hospital, Beijing, said.

The results were presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held online and in Orlando, and published simultaneously in The Lancet.

Although pressure wire–based physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR) more accurately identify flow-limiting lesions than standard angiography and have been shown to improve outcomes after PCI, the authors note that it’s underused in practice because of prolonged procedural time, potential pressure wire complications, and side effects from hyperemic agents.

QFR, however, is derived from 3-dimensional coronary artery reconstruction and computational fluid dynamics from the angiogram, so FFR can be estimated without the need for a pressure wire or hyperemic drugs.

FAVOR III China was designed statistically for superiority and enrolled 3,847 patients with stable or unstable angina or a myocardial infarction (MI) at least 72 hours before screening if they had at least one coronary lesion with a diameter stenosis of 50% to 90% and a reference vessel diameter of at least 2.5 mm. The intention-to-treat population included 3,825 patients (mean age, 62.7 years; 29.4% female).

In the QFR group, QFR was measured in all coronary arteries with a lesion but PCI performed only in lesions with a QFR of at least 0.80 or diameter stenosis greater than 90%. Two angiographic imaging runs were taken and the data transmitted to the AngioPlus system (Pulse Medical Imaging Technology) by a local network of sites for QFR calculation.

PCI in the angiography-guided group was performed on the basis of visual angiographic assessment only. A 10-minute delay was used in both groups to preserve masking.

The primary endpoint of 1-year MACE, a composite of all-cause death, MI, or ischemia-driven revascularization, occurred in 5.8% of the QFR-guided group and 8.8% of the angiography-guided group (hazard ratio, 0.65; 95% CI, 0.51-0.83; P = .0004).

The curves separated within 48 hours, driven largely by fewer MIs (3.4% vs. 5.7%; P = .0008) and ischemia-driven revascularizations (2.0% vs. 3.1%; P = .0078) in the QFR-guided group, Mr. Xu said.

The major secondary endpoint of MACE excluding periprocedural MI occurred in 3.1% of QFR-guided patients and 4.8% of angiography-guided patients (HR, 0.64; 95% CI, 0.46-0.89; P = .0073).

The prerandomization revascularization plan was changed in 23.3% of patients with QFR and only 6.2% in the angiography group (P < .0001), mainly due to deferral of treatment of at least one vessel originally planned for PCI (19.6% vs. 5.2%; P < .0001).

“I think in the next guideline they will change the recommendation, not just to include FFR and IFR, but also to include QFR,” Giuseppe Tarantini, MD, PhD, University of Padua, Italy, said during a press briefing on the study.

“This is a milestone in our community, not only because it is easier to use compared to the other lesion-specific indexes like FFR, IFR, but also for the need to expand the use of physiology in the setting of interventional cardiology,” he added.

In an accompanying commentary, Robert A. Byrne, MBBCh, PhD, and Laurna McGovern, MBBCh, both from the Cardiovascular Research Institute Dublin, say the results are “relevant for cardiovascular disease researchers and clinicians and an important step forward for the field of angiography-derived flow measurements for guidance of PCI.”

They point out, however, that the control group did not receive pressure wire–guided PCI, which is the standard of care in contemporary practice and out of step with clinical practice guidelines, thus limiting external validity.

They also note that experiences to date suggest that up to 20% of patients may be unsuitable for the algorithm analysis because of coronary anatomy, presence of overlapping vessels, and insufficient image quality.

Commenting for this news organization, David E. Kandzari, MD, chief of the Piedmont Heart Institute, Atlanta, said “the technology isn’t readily available in catheterization labs today. Could it be assimilated into the cath labs at one point in the near term? I think absolutely, and that would be a welcome addition to expedite the procedure itself.”

Nevertheless, he said the results “need to be externally validated too, with what is the gold standard today of FFR in a larger experience.”

Session moderator Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said FAVOR III China has “advanced our knowledge” but pointed out that the ongoing randomized FAVOR III Europe Japan study is directly comparing QFR with invasive pressure-wire assessed FFR. The estimated primary completion date for that study is Dec. 31.

The study was supported by grants from the Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital. Dr. Byrne reported institutional research or educational funding from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific. Ms. McGovern has disclosed no relevant financial relationships. Dr. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support.

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

Percutaneous coronary intervention (PCI) guided by quantitative flow ratio (QFR) lesion assessment provided better clinical outcomes than visual assessment of the angiogram in the sham-controlled FAVOR III China study.

PCI success rates were about 95% with both strategies; however, QFR guidance was associated with fewer major adverse cardiac events (MACE) at 1 year, use of fewer stents, less contrast medium exposure, and fewer procedural complications.

“The simplicity and safety of QFR compared with wire-based physiologic measurements should facilitate the adoption of physiologic lesion assessment into routine clinical practice,” co–primary investigator Bo Xu, MBBS, Fuwai Hospital, Beijing, said.

The results were presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held online and in Orlando, and published simultaneously in The Lancet.

Although pressure wire–based physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR) more accurately identify flow-limiting lesions than standard angiography and have been shown to improve outcomes after PCI, the authors note that it’s underused in practice because of prolonged procedural time, potential pressure wire complications, and side effects from hyperemic agents.

QFR, however, is derived from 3-dimensional coronary artery reconstruction and computational fluid dynamics from the angiogram, so FFR can be estimated without the need for a pressure wire or hyperemic drugs.

FAVOR III China was designed statistically for superiority and enrolled 3,847 patients with stable or unstable angina or a myocardial infarction (MI) at least 72 hours before screening if they had at least one coronary lesion with a diameter stenosis of 50% to 90% and a reference vessel diameter of at least 2.5 mm. The intention-to-treat population included 3,825 patients (mean age, 62.7 years; 29.4% female).

In the QFR group, QFR was measured in all coronary arteries with a lesion but PCI performed only in lesions with a QFR of at least 0.80 or diameter stenosis greater than 90%. Two angiographic imaging runs were taken and the data transmitted to the AngioPlus system (Pulse Medical Imaging Technology) by a local network of sites for QFR calculation.

PCI in the angiography-guided group was performed on the basis of visual angiographic assessment only. A 10-minute delay was used in both groups to preserve masking.

The primary endpoint of 1-year MACE, a composite of all-cause death, MI, or ischemia-driven revascularization, occurred in 5.8% of the QFR-guided group and 8.8% of the angiography-guided group (hazard ratio, 0.65; 95% CI, 0.51-0.83; P = .0004).

The curves separated within 48 hours, driven largely by fewer MIs (3.4% vs. 5.7%; P = .0008) and ischemia-driven revascularizations (2.0% vs. 3.1%; P = .0078) in the QFR-guided group, Mr. Xu said.

The major secondary endpoint of MACE excluding periprocedural MI occurred in 3.1% of QFR-guided patients and 4.8% of angiography-guided patients (HR, 0.64; 95% CI, 0.46-0.89; P = .0073).

The prerandomization revascularization plan was changed in 23.3% of patients with QFR and only 6.2% in the angiography group (P < .0001), mainly due to deferral of treatment of at least one vessel originally planned for PCI (19.6% vs. 5.2%; P < .0001).

“I think in the next guideline they will change the recommendation, not just to include FFR and IFR, but also to include QFR,” Giuseppe Tarantini, MD, PhD, University of Padua, Italy, said during a press briefing on the study.

“This is a milestone in our community, not only because it is easier to use compared to the other lesion-specific indexes like FFR, IFR, but also for the need to expand the use of physiology in the setting of interventional cardiology,” he added.

In an accompanying commentary, Robert A. Byrne, MBBCh, PhD, and Laurna McGovern, MBBCh, both from the Cardiovascular Research Institute Dublin, say the results are “relevant for cardiovascular disease researchers and clinicians and an important step forward for the field of angiography-derived flow measurements for guidance of PCI.”

They point out, however, that the control group did not receive pressure wire–guided PCI, which is the standard of care in contemporary practice and out of step with clinical practice guidelines, thus limiting external validity.

They also note that experiences to date suggest that up to 20% of patients may be unsuitable for the algorithm analysis because of coronary anatomy, presence of overlapping vessels, and insufficient image quality.

Commenting for this news organization, David E. Kandzari, MD, chief of the Piedmont Heart Institute, Atlanta, said “the technology isn’t readily available in catheterization labs today. Could it be assimilated into the cath labs at one point in the near term? I think absolutely, and that would be a welcome addition to expedite the procedure itself.”

Nevertheless, he said the results “need to be externally validated too, with what is the gold standard today of FFR in a larger experience.”

Session moderator Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said FAVOR III China has “advanced our knowledge” but pointed out that the ongoing randomized FAVOR III Europe Japan study is directly comparing QFR with invasive pressure-wire assessed FFR. The estimated primary completion date for that study is Dec. 31.

The study was supported by grants from the Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital. Dr. Byrne reported institutional research or educational funding from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific. Ms. McGovern has disclosed no relevant financial relationships. Dr. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support.

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

Percutaneous coronary intervention (PCI) guided by quantitative flow ratio (QFR) lesion assessment provided better clinical outcomes than visual assessment of the angiogram in the sham-controlled FAVOR III China study.

PCI success rates were about 95% with both strategies; however, QFR guidance was associated with fewer major adverse cardiac events (MACE) at 1 year, use of fewer stents, less contrast medium exposure, and fewer procedural complications.

“The simplicity and safety of QFR compared with wire-based physiologic measurements should facilitate the adoption of physiologic lesion assessment into routine clinical practice,” co–primary investigator Bo Xu, MBBS, Fuwai Hospital, Beijing, said.

The results were presented at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held online and in Orlando, and published simultaneously in The Lancet.

Although pressure wire–based physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR) more accurately identify flow-limiting lesions than standard angiography and have been shown to improve outcomes after PCI, the authors note that it’s underused in practice because of prolonged procedural time, potential pressure wire complications, and side effects from hyperemic agents.

QFR, however, is derived from 3-dimensional coronary artery reconstruction and computational fluid dynamics from the angiogram, so FFR can be estimated without the need for a pressure wire or hyperemic drugs.

FAVOR III China was designed statistically for superiority and enrolled 3,847 patients with stable or unstable angina or a myocardial infarction (MI) at least 72 hours before screening if they had at least one coronary lesion with a diameter stenosis of 50% to 90% and a reference vessel diameter of at least 2.5 mm. The intention-to-treat population included 3,825 patients (mean age, 62.7 years; 29.4% female).

In the QFR group, QFR was measured in all coronary arteries with a lesion but PCI performed only in lesions with a QFR of at least 0.80 or diameter stenosis greater than 90%. Two angiographic imaging runs were taken and the data transmitted to the AngioPlus system (Pulse Medical Imaging Technology) by a local network of sites for QFR calculation.

PCI in the angiography-guided group was performed on the basis of visual angiographic assessment only. A 10-minute delay was used in both groups to preserve masking.

The primary endpoint of 1-year MACE, a composite of all-cause death, MI, or ischemia-driven revascularization, occurred in 5.8% of the QFR-guided group and 8.8% of the angiography-guided group (hazard ratio, 0.65; 95% CI, 0.51-0.83; P = .0004).

The curves separated within 48 hours, driven largely by fewer MIs (3.4% vs. 5.7%; P = .0008) and ischemia-driven revascularizations (2.0% vs. 3.1%; P = .0078) in the QFR-guided group, Mr. Xu said.

The major secondary endpoint of MACE excluding periprocedural MI occurred in 3.1% of QFR-guided patients and 4.8% of angiography-guided patients (HR, 0.64; 95% CI, 0.46-0.89; P = .0073).

The prerandomization revascularization plan was changed in 23.3% of patients with QFR and only 6.2% in the angiography group (P < .0001), mainly due to deferral of treatment of at least one vessel originally planned for PCI (19.6% vs. 5.2%; P < .0001).

“I think in the next guideline they will change the recommendation, not just to include FFR and IFR, but also to include QFR,” Giuseppe Tarantini, MD, PhD, University of Padua, Italy, said during a press briefing on the study.

“This is a milestone in our community, not only because it is easier to use compared to the other lesion-specific indexes like FFR, IFR, but also for the need to expand the use of physiology in the setting of interventional cardiology,” he added.

In an accompanying commentary, Robert A. Byrne, MBBCh, PhD, and Laurna McGovern, MBBCh, both from the Cardiovascular Research Institute Dublin, say the results are “relevant for cardiovascular disease researchers and clinicians and an important step forward for the field of angiography-derived flow measurements for guidance of PCI.”

They point out, however, that the control group did not receive pressure wire–guided PCI, which is the standard of care in contemporary practice and out of step with clinical practice guidelines, thus limiting external validity.

They also note that experiences to date suggest that up to 20% of patients may be unsuitable for the algorithm analysis because of coronary anatomy, presence of overlapping vessels, and insufficient image quality.

Commenting for this news organization, David E. Kandzari, MD, chief of the Piedmont Heart Institute, Atlanta, said “the technology isn’t readily available in catheterization labs today. Could it be assimilated into the cath labs at one point in the near term? I think absolutely, and that would be a welcome addition to expedite the procedure itself.”

Nevertheless, he said the results “need to be externally validated too, with what is the gold standard today of FFR in a larger experience.”

Session moderator Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said FAVOR III China has “advanced our knowledge” but pointed out that the ongoing randomized FAVOR III Europe Japan study is directly comparing QFR with invasive pressure-wire assessed FFR. The estimated primary completion date for that study is Dec. 31.

The study was supported by grants from the Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital. Dr. Byrne reported institutional research or educational funding from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific. Ms. McGovern has disclosed no relevant financial relationships. Dr. Kandzari reported minor consulting honoraria from the interventional device industry and institutional research grant support.

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

More than half of people living with HIV and suppressed viral loads nonetheless had imaging-confirmed coronary artery disease – and despite longtime use of HIV drugs that have been associated with cardiovascular trouble, none of those drugs were implicated in disease risk in this study.

“Traditional risk factors and duration of HIV infection were associated with severe coronary artery disease,” said Andreas Knudsen, MD, PhD, an infectious disease provider at Copenhagen University Hospital, Hvidovre, Denmark, during his presentation at the 18th European AIDS Conference. “When we adjusted for time since diagnosis of HIV, none of the drugs remained associated with the severity of coronary artery disease.”

Notably, that included abacavir, which was found in another EACS presentation and in past research to be associated with increased rates of heart attacks. Abacavir is sold individually as a generic as well as a component of Epzicom (abacavir/lamivudine) and the single-drug regimen Triumeq (dolutegravir/abacavir/lamivudine).

The Copenhagen Comorbidity in HIV Infection (COCOMO) study enrolled 1,099 people living with HIV in the Danish capital beginning in 2015, and 705 of them had angiographies via CT available to include in the results. The participants were almost all male (89%), at a healthy weight (BMI of 25), and 96% had undetectable viral loads.

Large minorities of participants also had traditional risk factors for coronary artery disease. More than one in four smoked, one in five had high cholesterol, and 42% had high blood pressure. In addition, many had used drugs that have been associated with cardiovascular trouble, including abacavir, which 26% of participants had used; indinavir, used by 17% of participants; zidovudine/AZT, used by 47%; and didanosine, which 14% used. (While abacavir is still in use, the other three drugs are considered legacy drugs and are not in current use.)

In addition, nearly one in three (29%) were currently using a protease inhibitor, which has been associated with heart failure.

When the investigators looked at participants’ CTs, they found that, by the Coronary Artery Disease-Reporting and Data Systems (CAD-RAMS) scoring system, close to half (46%) had clear arteries with no signs of coronary artery disease. But that also meant that 54% had some blockage or stiffening of the arteries. The good news is that 27% of those people had minimal or mild coronary artery disease.

But a full 17% had confirmed obstructive coronary artery disease, and another 1 in 10 participants had the highest level of blockages. When they broke the data down by traditional and HIV medication–related risk factors for coronary artery disease, they found something interesting. Although obesity was associated with the presence of atherosclerosis, it wasn’t associated with severe disease. But diabetes was the reverse of that: It wasn’t associated with the presence of the disease, but it was associated with more severe disease.

And when they looked at abacavir, they found no relationship between the drug and atherosclerosis. “Abacavir was not associated with the presence of atherosclerosis and was also not associated with severity of disease,” said Dr. Knudsen.

Although past use of AZT, indinavir, and didanosine were associated with severity of atherosclerosis, that association went away when Dr. Knudsen and team adjusted the findings for time since diagnosis. What was associated atherosclerosis was length of time living with HIV itself. For every 5 years a person lived with HIV, the study found the risk of having any atherosclerosis increased 20% and severity increased 23%. In addition, being a man was associated with a nearly 2.5-times increased risk of having any atherosclerosis and a 96% increased chance of having more severe atherosclerosis. Having diabetes was associated with a nearly threefold increased risk of atherosclerosis, as was every additional decade of life for a person who was living with HIV.

The findings confirm the baseline data of the REPRIEVE trial, which recently released data showing similarly high rates of atherosclerotic plaque in people living with HIV who didn’t register as “at risk” for cardiovascular disease using traditional scoring methods.

“It’s important in that it’s a huge study that’s confirmatory [of] what we know, which is that there are high levels of subclinical coronary artery disease in people living with HIV,” said Steven Grinspoon, MD, professor at Harvard Medical School in Boston, Massachusetts, and principal investigator of REPRIEVE.

As for the lack of association between abacavir and cardiovascular risk, he said he’s taking the findings with a grain of salt.

“It’s hard to make a lot out of that,” he said. “It’s hard to know in a cross-sectional study. People put people on different things.”

In Spain, where Jose Ignacio Bernardino, MD, treats people living with HIV at La Paz University Hospital in Madrid, abacavir is mostly a moot point, as clinicians have long since moved away from maintaining people living with HIV on any abacavir-containing regimens. What’s more important in the study, he told this news organization, is that “worrisome” high level of risk. REPRIEVE will test whether statins can reduce heart disease events in people living with HIV. But in the meantime, he said the take-away for clinicians from the study is the primary importance of traditional cardiovascular risk factors.

“We have to acknowledge that the major cardiovascular risk factor is age,” he said. “When patients are approaching their 50s, I usually try to stress a lot about cardiovascular risk factors in general. I stress healthy lifestyle – get physical exercise, hypertension, glucose, lipids – in every single patient.”

Dr. Knudsen and Dr. Bernardino have disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

More than half of people living with HIV and suppressed viral loads nonetheless had imaging-confirmed coronary artery disease – and despite longtime use of HIV drugs that have been associated with cardiovascular trouble, none of those drugs were implicated in disease risk in this study.

“Traditional risk factors and duration of HIV infection were associated with severe coronary artery disease,” said Andreas Knudsen, MD, PhD, an infectious disease provider at Copenhagen University Hospital, Hvidovre, Denmark, during his presentation at the 18th European AIDS Conference. “When we adjusted for time since diagnosis of HIV, none of the drugs remained associated with the severity of coronary artery disease.”

Notably, that included abacavir, which was found in another EACS presentation and in past research to be associated with increased rates of heart attacks. Abacavir is sold individually as a generic as well as a component of Epzicom (abacavir/lamivudine) and the single-drug regimen Triumeq (dolutegravir/abacavir/lamivudine).

The Copenhagen Comorbidity in HIV Infection (COCOMO) study enrolled 1,099 people living with HIV in the Danish capital beginning in 2015, and 705 of them had angiographies via CT available to include in the results. The participants were almost all male (89%), at a healthy weight (BMI of 25), and 96% had undetectable viral loads.

Large minorities of participants also had traditional risk factors for coronary artery disease. More than one in four smoked, one in five had high cholesterol, and 42% had high blood pressure. In addition, many had used drugs that have been associated with cardiovascular trouble, including abacavir, which 26% of participants had used; indinavir, used by 17% of participants; zidovudine/AZT, used by 47%; and didanosine, which 14% used. (While abacavir is still in use, the other three drugs are considered legacy drugs and are not in current use.)

In addition, nearly one in three (29%) were currently using a protease inhibitor, which has been associated with heart failure.

When the investigators looked at participants’ CTs, they found that, by the Coronary Artery Disease-Reporting and Data Systems (CAD-RAMS) scoring system, close to half (46%) had clear arteries with no signs of coronary artery disease. But that also meant that 54% had some blockage or stiffening of the arteries. The good news is that 27% of those people had minimal or mild coronary artery disease.

But a full 17% had confirmed obstructive coronary artery disease, and another 1 in 10 participants had the highest level of blockages. When they broke the data down by traditional and HIV medication–related risk factors for coronary artery disease, they found something interesting. Although obesity was associated with the presence of atherosclerosis, it wasn’t associated with severe disease. But diabetes was the reverse of that: It wasn’t associated with the presence of the disease, but it was associated with more severe disease.

And when they looked at abacavir, they found no relationship between the drug and atherosclerosis. “Abacavir was not associated with the presence of atherosclerosis and was also not associated with severity of disease,” said Dr. Knudsen.

Although past use of AZT, indinavir, and didanosine were associated with severity of atherosclerosis, that association went away when Dr. Knudsen and team adjusted the findings for time since diagnosis. What was associated atherosclerosis was length of time living with HIV itself. For every 5 years a person lived with HIV, the study found the risk of having any atherosclerosis increased 20% and severity increased 23%. In addition, being a man was associated with a nearly 2.5-times increased risk of having any atherosclerosis and a 96% increased chance of having more severe atherosclerosis. Having diabetes was associated with a nearly threefold increased risk of atherosclerosis, as was every additional decade of life for a person who was living with HIV.

The findings confirm the baseline data of the REPRIEVE trial, which recently released data showing similarly high rates of atherosclerotic plaque in people living with HIV who didn’t register as “at risk” for cardiovascular disease using traditional scoring methods.

“It’s important in that it’s a huge study that’s confirmatory [of] what we know, which is that there are high levels of subclinical coronary artery disease in people living with HIV,” said Steven Grinspoon, MD, professor at Harvard Medical School in Boston, Massachusetts, and principal investigator of REPRIEVE.

As for the lack of association between abacavir and cardiovascular risk, he said he’s taking the findings with a grain of salt.

“It’s hard to make a lot out of that,” he said. “It’s hard to know in a cross-sectional study. People put people on different things.”

In Spain, where Jose Ignacio Bernardino, MD, treats people living with HIV at La Paz University Hospital in Madrid, abacavir is mostly a moot point, as clinicians have long since moved away from maintaining people living with HIV on any abacavir-containing regimens. What’s more important in the study, he told this news organization, is that “worrisome” high level of risk. REPRIEVE will test whether statins can reduce heart disease events in people living with HIV. But in the meantime, he said the take-away for clinicians from the study is the primary importance of traditional cardiovascular risk factors.

“We have to acknowledge that the major cardiovascular risk factor is age,” he said. “When patients are approaching their 50s, I usually try to stress a lot about cardiovascular risk factors in general. I stress healthy lifestyle – get physical exercise, hypertension, glucose, lipids – in every single patient.”

Dr. Knudsen and Dr. Bernardino have disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

More than half of people living with HIV and suppressed viral loads nonetheless had imaging-confirmed coronary artery disease – and despite longtime use of HIV drugs that have been associated with cardiovascular trouble, none of those drugs were implicated in disease risk in this study.

“Traditional risk factors and duration of HIV infection were associated with severe coronary artery disease,” said Andreas Knudsen, MD, PhD, an infectious disease provider at Copenhagen University Hospital, Hvidovre, Denmark, during his presentation at the 18th European AIDS Conference. “When we adjusted for time since diagnosis of HIV, none of the drugs remained associated with the severity of coronary artery disease.”

Notably, that included abacavir, which was found in another EACS presentation and in past research to be associated with increased rates of heart attacks. Abacavir is sold individually as a generic as well as a component of Epzicom (abacavir/lamivudine) and the single-drug regimen Triumeq (dolutegravir/abacavir/lamivudine).

The Copenhagen Comorbidity in HIV Infection (COCOMO) study enrolled 1,099 people living with HIV in the Danish capital beginning in 2015, and 705 of them had angiographies via CT available to include in the results. The participants were almost all male (89%), at a healthy weight (BMI of 25), and 96% had undetectable viral loads.

Large minorities of participants also had traditional risk factors for coronary artery disease. More than one in four smoked, one in five had high cholesterol, and 42% had high blood pressure. In addition, many had used drugs that have been associated with cardiovascular trouble, including abacavir, which 26% of participants had used; indinavir, used by 17% of participants; zidovudine/AZT, used by 47%; and didanosine, which 14% used. (While abacavir is still in use, the other three drugs are considered legacy drugs and are not in current use.)

In addition, nearly one in three (29%) were currently using a protease inhibitor, which has been associated with heart failure.

When the investigators looked at participants’ CTs, they found that, by the Coronary Artery Disease-Reporting and Data Systems (CAD-RAMS) scoring system, close to half (46%) had clear arteries with no signs of coronary artery disease. But that also meant that 54% had some blockage or stiffening of the arteries. The good news is that 27% of those people had minimal or mild coronary artery disease.

But a full 17% had confirmed obstructive coronary artery disease, and another 1 in 10 participants had the highest level of blockages. When they broke the data down by traditional and HIV medication–related risk factors for coronary artery disease, they found something interesting. Although obesity was associated with the presence of atherosclerosis, it wasn’t associated with severe disease. But diabetes was the reverse of that: It wasn’t associated with the presence of the disease, but it was associated with more severe disease.

And when they looked at abacavir, they found no relationship between the drug and atherosclerosis. “Abacavir was not associated with the presence of atherosclerosis and was also not associated with severity of disease,” said Dr. Knudsen.

Although past use of AZT, indinavir, and didanosine were associated with severity of atherosclerosis, that association went away when Dr. Knudsen and team adjusted the findings for time since diagnosis. What was associated atherosclerosis was length of time living with HIV itself. For every 5 years a person lived with HIV, the study found the risk of having any atherosclerosis increased 20% and severity increased 23%. In addition, being a man was associated with a nearly 2.5-times increased risk of having any atherosclerosis and a 96% increased chance of having more severe atherosclerosis. Having diabetes was associated with a nearly threefold increased risk of atherosclerosis, as was every additional decade of life for a person who was living with HIV.

The findings confirm the baseline data of the REPRIEVE trial, which recently released data showing similarly high rates of atherosclerotic plaque in people living with HIV who didn’t register as “at risk” for cardiovascular disease using traditional scoring methods.

“It’s important in that it’s a huge study that’s confirmatory [of] what we know, which is that there are high levels of subclinical coronary artery disease in people living with HIV,” said Steven Grinspoon, MD, professor at Harvard Medical School in Boston, Massachusetts, and principal investigator of REPRIEVE.

As for the lack of association between abacavir and cardiovascular risk, he said he’s taking the findings with a grain of salt.

“It’s hard to make a lot out of that,” he said. “It’s hard to know in a cross-sectional study. People put people on different things.”

In Spain, where Jose Ignacio Bernardino, MD, treats people living with HIV at La Paz University Hospital in Madrid, abacavir is mostly a moot point, as clinicians have long since moved away from maintaining people living with HIV on any abacavir-containing regimens. What’s more important in the study, he told this news organization, is that “worrisome” high level of risk. REPRIEVE will test whether statins can reduce heart disease events in people living with HIV. But in the meantime, he said the take-away for clinicians from the study is the primary importance of traditional cardiovascular risk factors.

“We have to acknowledge that the major cardiovascular risk factor is age,” he said. “When patients are approaching their 50s, I usually try to stress a lot about cardiovascular risk factors in general. I stress healthy lifestyle – get physical exercise, hypertension, glucose, lipids – in every single patient.”

Dr. Knudsen and Dr. Bernardino have disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

The effectiveness of COVID-19 vaccines produced by Pfizer/BioNTech, Moderna, and Johnson & Johnson dropped dramatically as the Delta variant swept the United States, a study of almost 800,000 veterans found.

The study, published in the journal Science ., says the three vaccines offered about the same protection against the virus in March, when the Delta variant was first detected in the United States, but that changed 6 months later.

The Moderna two-dose vaccine went from being 89% effective in March to 58% effective in September, according to a story about the study in theLos Angeles Times.

Meanwhile, the Pfizer/BioNTech vaccine went from being 87% effective to 45% effective over the same time period.

The Johnson & Johnson vaccine showed the biggest drop -- from 86% effectiveness to 13% over those 6 months.

“In summary, although vaccination remains protective against SARS-CoV-2 infection, protection waned as the Delta variant emerged in the U.S., and this decline did not differ by age,” the study said.

The three vaccines also lost effectiveness in the ability to protect against death in veterans 65 and over after only 3 months, the Los Angeles Times reported.

Compared to unvaccinated veterans in that age group, veterans who got the Moderna vaccine and had a breakthrough case were 76% less likely to die of COVID-19 by July.

The protection was 70% for Pfizer/BioNTech vaccine recipients and 52% for J&J vaccine recipients for the same age group, compared to unvaccinated veterans, according to the newspaper.

For veterans under 65, the protectiveness against a fatal case of COVID was 84% for Pfizer/BioNTech recipients, 82% for Moderna recipients, and 73% for J&J recipients, compared to unvaccinated veterans in that age group.

The study confirms the need for booster vaccines and protective measures such as vaccine passports, vaccine mandates, masking, hand-washing, and social distancing, the researchers said.

Of the veterans studied, about 500,000 were vaccinated and 300,000 were not. Researchers noted that the study population had 6 times as many men as women. About 48% of the study group was 65 or older, 29% was 50-64, while 24% was under 50.

Researchers from the Public Health Institute in Oakland, the Veterans Affairs Medical Center in San Francisco, and the University of Texas Health Science Center conducted the study.

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

The effectiveness of COVID-19 vaccines produced by Pfizer/BioNTech, Moderna, and Johnson & Johnson dropped dramatically as the Delta variant swept the United States, a study of almost 800,000 veterans found.

The study, published in the journal Science ., says the three vaccines offered about the same protection against the virus in March, when the Delta variant was first detected in the United States, but that changed 6 months later.

The Moderna two-dose vaccine went from being 89% effective in March to 58% effective in September, according to a story about the study in theLos Angeles Times.

Meanwhile, the Pfizer/BioNTech vaccine went from being 87% effective to 45% effective over the same time period.

The Johnson & Johnson vaccine showed the biggest drop -- from 86% effectiveness to 13% over those 6 months.

“In summary, although vaccination remains protective against SARS-CoV-2 infection, protection waned as the Delta variant emerged in the U.S., and this decline did not differ by age,” the study said.

The three vaccines also lost effectiveness in the ability to protect against death in veterans 65 and over after only 3 months, the Los Angeles Times reported.

Compared to unvaccinated veterans in that age group, veterans who got the Moderna vaccine and had a breakthrough case were 76% less likely to die of COVID-19 by July.

The protection was 70% for Pfizer/BioNTech vaccine recipients and 52% for J&J vaccine recipients for the same age group, compared to unvaccinated veterans, according to the newspaper.

For veterans under 65, the protectiveness against a fatal case of COVID was 84% for Pfizer/BioNTech recipients, 82% for Moderna recipients, and 73% for J&J recipients, compared to unvaccinated veterans in that age group.

The study confirms the need for booster vaccines and protective measures such as vaccine passports, vaccine mandates, masking, hand-washing, and social distancing, the researchers said.

Of the veterans studied, about 500,000 were vaccinated and 300,000 were not. Researchers noted that the study population had 6 times as many men as women. About 48% of the study group was 65 or older, 29% was 50-64, while 24% was under 50.

Researchers from the Public Health Institute in Oakland, the Veterans Affairs Medical Center in San Francisco, and the University of Texas Health Science Center conducted the study.

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

The effectiveness of COVID-19 vaccines produced by Pfizer/BioNTech, Moderna, and Johnson & Johnson dropped dramatically as the Delta variant swept the United States, a study of almost 800,000 veterans found.

The study, published in the journal Science ., says the three vaccines offered about the same protection against the virus in March, when the Delta variant was first detected in the United States, but that changed 6 months later.

The Moderna two-dose vaccine went from being 89% effective in March to 58% effective in September, according to a story about the study in theLos Angeles Times.

Meanwhile, the Pfizer/BioNTech vaccine went from being 87% effective to 45% effective over the same time period.

The Johnson & Johnson vaccine showed the biggest drop -- from 86% effectiveness to 13% over those 6 months.

“In summary, although vaccination remains protective against SARS-CoV-2 infection, protection waned as the Delta variant emerged in the U.S., and this decline did not differ by age,” the study said.

The three vaccines also lost effectiveness in the ability to protect against death in veterans 65 and over after only 3 months, the Los Angeles Times reported.

Compared to unvaccinated veterans in that age group, veterans who got the Moderna vaccine and had a breakthrough case were 76% less likely to die of COVID-19 by July.

The protection was 70% for Pfizer/BioNTech vaccine recipients and 52% for J&J vaccine recipients for the same age group, compared to unvaccinated veterans, according to the newspaper.

For veterans under 65, the protectiveness against a fatal case of COVID was 84% for Pfizer/BioNTech recipients, 82% for Moderna recipients, and 73% for J&J recipients, compared to unvaccinated veterans in that age group.

The study confirms the need for booster vaccines and protective measures such as vaccine passports, vaccine mandates, masking, hand-washing, and social distancing, the researchers said.

Of the veterans studied, about 500,000 were vaccinated and 300,000 were not. Researchers noted that the study population had 6 times as many men as women. About 48% of the study group was 65 or older, 29% was 50-64, while 24% was under 50.

Researchers from the Public Health Institute in Oakland, the Veterans Affairs Medical Center in San Francisco, and the University of Texas Health Science Center conducted the study.

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

Certain antihypertensive medications, particularly diuretics, are linked to lower Alzheimer’s disease neuropathology and other brain disease processes, new research shows.

Investigators found that use of any antihypertensive was associated with an 18% decrease in Alzheimer’s disease neuropathology, a 22% decrease in Lewy bodies, and a 40% decrease in TAR DNA-binding protein 43 (TDP-43), a protein relevant to several neurodegenerative diseases. Diuretics in particular appear to be driving the association.

Although diuretics might be a better option for preventing brain neuropathology, it’s too early to make firm recommendations solely on the basis of these results as to what blood pressure–lowering agent to prescribe a particular patient, said study investigator Ahmad Sajjadi, MD, assistant professor of neurology, University of California, Irvine.

“This is early stages and preliminary results,” said Dr. Sajjadi, “but it’s food for thought.”

The findings were presented at the 2021 annual meeting of the American Neurological Association.
 

Autopsy data

The study included 3,315 individuals who had donated their brains to research. The National Alzheimer’s Coordinating Center maintains a database that includes data from 32 Alzheimer’s disease research centers in the United States. Participants in the study must have visited one of these centers within 4 years of death. Each person whose brain was included in the study underwent two or more BP measurements on at least 50% of visits.

The mean age at death was 81.7 years, and the mean time between last visit and death was 13.1 months. About 44.4% of participants were women, 57.0% had at least a college degree, and 84.7% had cognitive impairment.

Researchers defined hypertension as systolic BP of at least 130 mm Hg, diastolic BP of at least 80 mm Hg, mean arterial pressure of at least 100 mm Hg, and pulse pressure of at least 60 mm Hg.

Antihypertensive medications that were evaluated included antiadrenergic agents, ACE inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, diuretics, vasodilators, and combination therapies.

The investigators assessed the number of neuropathologies. In addition to Alzheimer’s disease neuropathology, which included amyloid-beta, tau, Lewy bodies, and TDP-43, they also assessed for atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, frontotemporal lobar degeneration, and hippocampal sclerosis.

Results showed that use of any antihypertensive was associated with a lower likelihood of Alzheimer’s disease neuropathology (odds ratio, 0.822), Lewy bodies (OR, 0.786), and TDP 43 (OR, 0.597). Use of antihypertensives was also associated with increased odds of atherosclerosis (OR, 1.217) (all P < .5.)

The study showed that hypertensive systolic BP was associated with higher odds of Alzheimer’s disease neuropathology (OR, 1.28; P < .5).

Differences by drug type

Results differed in accordance with antihypertensive class. Angiotensin II receptor blockers decreased the odds of Alzheimer’s disease neuropathology by 40% (OR, 0.60; P < .5). Diuretics decreased the odds of Alzheimer’s disease by 36% (OR, 0.64; P < .001) and of hippocampal sclerosis by 32% (OR, 0.68; P < .5).

“We see diuretics are a main driver, especially for lower odds of Alzheimer’s disease and lower odds of hippocampal sclerosis,” said lead author Hanna L. Nguyen, a first-year medical student at the University of California, Irvine.

The results indicate that it is the medications, not BP levels, that account for these associations, she added.

One potential mechanism linking antihypertensives to brain pathology is that with these agents, BP is maintained in the target zone. Blood pressure that’s too high can damage blood vessels, whereas BP that’s too low may result in less than adequate perfusion, said Ms. Nguyen.

These medications may also alter pathways leading to degeneration and could, for example, affect the apo E mechanism of Alzheimer’s disease, she added.

The researchers plan to conduct subset analyses using apo E genetic status and age of death.

Although this is a “massive database,” it has limitations. For example, said Dr. Sajjadi, it does not reveal when patients started taking BP medication, how long they had been taking it, or why.

“We don’t know the exact the reason they were taking these medications. Was it just hypertension, or did they also have heart disease, stroke, a kidney problem, or was there another explanation,” he said.

Following the study presentation, session comoderator Krish Sathian, MBBS, PhD, professor of neurology, neural, and behavioral sciences, and psychology and director of the Neuroscience Institute, Penn State University, Hershey, called this work “fascinating. It provides a lot of data that really touches on everyday practice,” inasmuch as clinicians often prescribe antihypertensive medications and see patients with these kinds of brain disorders.

The investigators and Dr. Sathian reported no relevant financial relationships.

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

Certain antihypertensive medications, particularly diuretics, are linked to lower Alzheimer’s disease neuropathology and other brain disease processes, new research shows.

Investigators found that use of any antihypertensive was associated with an 18% decrease in Alzheimer’s disease neuropathology, a 22% decrease in Lewy bodies, and a 40% decrease in TAR DNA-binding protein 43 (TDP-43), a protein relevant to several neurodegenerative diseases. Diuretics in particular appear to be driving the association.

Although diuretics might be a better option for preventing brain neuropathology, it’s too early to make firm recommendations solely on the basis of these results as to what blood pressure–lowering agent to prescribe a particular patient, said study investigator Ahmad Sajjadi, MD, assistant professor of neurology, University of California, Irvine.

“This is early stages and preliminary results,” said Dr. Sajjadi, “but it’s food for thought.”

The findings were presented at the 2021 annual meeting of the American Neurological Association.
 

Autopsy data

The study included 3,315 individuals who had donated their brains to research. The National Alzheimer’s Coordinating Center maintains a database that includes data from 32 Alzheimer’s disease research centers in the United States. Participants in the study must have visited one of these centers within 4 years of death. Each person whose brain was included in the study underwent two or more BP measurements on at least 50% of visits.

The mean age at death was 81.7 years, and the mean time between last visit and death was 13.1 months. About 44.4% of participants were women, 57.0% had at least a college degree, and 84.7% had cognitive impairment.

Researchers defined hypertension as systolic BP of at least 130 mm Hg, diastolic BP of at least 80 mm Hg, mean arterial pressure of at least 100 mm Hg, and pulse pressure of at least 60 mm Hg.

Antihypertensive medications that were evaluated included antiadrenergic agents, ACE inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, diuretics, vasodilators, and combination therapies.

The investigators assessed the number of neuropathologies. In addition to Alzheimer’s disease neuropathology, which included amyloid-beta, tau, Lewy bodies, and TDP-43, they also assessed for atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, frontotemporal lobar degeneration, and hippocampal sclerosis.

Results showed that use of any antihypertensive was associated with a lower likelihood of Alzheimer’s disease neuropathology (odds ratio, 0.822), Lewy bodies (OR, 0.786), and TDP 43 (OR, 0.597). Use of antihypertensives was also associated with increased odds of atherosclerosis (OR, 1.217) (all P < .5.)

The study showed that hypertensive systolic BP was associated with higher odds of Alzheimer’s disease neuropathology (OR, 1.28; P < .5).

Differences by drug type

Results differed in accordance with antihypertensive class. Angiotensin II receptor blockers decreased the odds of Alzheimer’s disease neuropathology by 40% (OR, 0.60; P < .5). Diuretics decreased the odds of Alzheimer’s disease by 36% (OR, 0.64; P < .001) and of hippocampal sclerosis by 32% (OR, 0.68; P < .5).

“We see diuretics are a main driver, especially for lower odds of Alzheimer’s disease and lower odds of hippocampal sclerosis,” said lead author Hanna L. Nguyen, a first-year medical student at the University of California, Irvine.

The results indicate that it is the medications, not BP levels, that account for these associations, she added.

One potential mechanism linking antihypertensives to brain pathology is that with these agents, BP is maintained in the target zone. Blood pressure that’s too high can damage blood vessels, whereas BP that’s too low may result in less than adequate perfusion, said Ms. Nguyen.

These medications may also alter pathways leading to degeneration and could, for example, affect the apo E mechanism of Alzheimer’s disease, she added.

The researchers plan to conduct subset analyses using apo E genetic status and age of death.

Although this is a “massive database,” it has limitations. For example, said Dr. Sajjadi, it does not reveal when patients started taking BP medication, how long they had been taking it, or why.

“We don’t know the exact the reason they were taking these medications. Was it just hypertension, or did they also have heart disease, stroke, a kidney problem, or was there another explanation,” he said.

Following the study presentation, session comoderator Krish Sathian, MBBS, PhD, professor of neurology, neural, and behavioral sciences, and psychology and director of the Neuroscience Institute, Penn State University, Hershey, called this work “fascinating. It provides a lot of data that really touches on everyday practice,” inasmuch as clinicians often prescribe antihypertensive medications and see patients with these kinds of brain disorders.

The investigators and Dr. Sathian reported no relevant financial relationships.

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

Certain antihypertensive medications, particularly diuretics, are linked to lower Alzheimer’s disease neuropathology and other brain disease processes, new research shows.

Investigators found that use of any antihypertensive was associated with an 18% decrease in Alzheimer’s disease neuropathology, a 22% decrease in Lewy bodies, and a 40% decrease in TAR DNA-binding protein 43 (TDP-43), a protein relevant to several neurodegenerative diseases. Diuretics in particular appear to be driving the association.

Although diuretics might be a better option for preventing brain neuropathology, it’s too early to make firm recommendations solely on the basis of these results as to what blood pressure–lowering agent to prescribe a particular patient, said study investigator Ahmad Sajjadi, MD, assistant professor of neurology, University of California, Irvine.

“This is early stages and preliminary results,” said Dr. Sajjadi, “but it’s food for thought.”

The findings were presented at the 2021 annual meeting of the American Neurological Association.
 

Autopsy data

The study included 3,315 individuals who had donated their brains to research. The National Alzheimer’s Coordinating Center maintains a database that includes data from 32 Alzheimer’s disease research centers in the United States. Participants in the study must have visited one of these centers within 4 years of death. Each person whose brain was included in the study underwent two or more BP measurements on at least 50% of visits.

The mean age at death was 81.7 years, and the mean time between last visit and death was 13.1 months. About 44.4% of participants were women, 57.0% had at least a college degree, and 84.7% had cognitive impairment.

Researchers defined hypertension as systolic BP of at least 130 mm Hg, diastolic BP of at least 80 mm Hg, mean arterial pressure of at least 100 mm Hg, and pulse pressure of at least 60 mm Hg.

Antihypertensive medications that were evaluated included antiadrenergic agents, ACE inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, diuretics, vasodilators, and combination therapies.

The investigators assessed the number of neuropathologies. In addition to Alzheimer’s disease neuropathology, which included amyloid-beta, tau, Lewy bodies, and TDP-43, they also assessed for atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, frontotemporal lobar degeneration, and hippocampal sclerosis.

Results showed that use of any antihypertensive was associated with a lower likelihood of Alzheimer’s disease neuropathology (odds ratio, 0.822), Lewy bodies (OR, 0.786), and TDP 43 (OR, 0.597). Use of antihypertensives was also associated with increased odds of atherosclerosis (OR, 1.217) (all P < .5.)

The study showed that hypertensive systolic BP was associated with higher odds of Alzheimer’s disease neuropathology (OR, 1.28; P < .5).

Differences by drug type

Results differed in accordance with antihypertensive class. Angiotensin II receptor blockers decreased the odds of Alzheimer’s disease neuropathology by 40% (OR, 0.60; P < .5). Diuretics decreased the odds of Alzheimer’s disease by 36% (OR, 0.64; P < .001) and of hippocampal sclerosis by 32% (OR, 0.68; P < .5).

“We see diuretics are a main driver, especially for lower odds of Alzheimer’s disease and lower odds of hippocampal sclerosis,” said lead author Hanna L. Nguyen, a first-year medical student at the University of California, Irvine.

The results indicate that it is the medications, not BP levels, that account for these associations, she added.

One potential mechanism linking antihypertensives to brain pathology is that with these agents, BP is maintained in the target zone. Blood pressure that’s too high can damage blood vessels, whereas BP that’s too low may result in less than adequate perfusion, said Ms. Nguyen.

These medications may also alter pathways leading to degeneration and could, for example, affect the apo E mechanism of Alzheimer’s disease, she added.

The researchers plan to conduct subset analyses using apo E genetic status and age of death.

Although this is a “massive database,” it has limitations. For example, said Dr. Sajjadi, it does not reveal when patients started taking BP medication, how long they had been taking it, or why.

“We don’t know the exact the reason they were taking these medications. Was it just hypertension, or did they also have heart disease, stroke, a kidney problem, or was there another explanation,” he said.

Following the study presentation, session comoderator Krish Sathian, MBBS, PhD, professor of neurology, neural, and behavioral sciences, and psychology and director of the Neuroscience Institute, Penn State University, Hershey, called this work “fascinating. It provides a lot of data that really touches on everyday practice,” inasmuch as clinicians often prescribe antihypertensive medications and see patients with these kinds of brain disorders.

The investigators and Dr. Sathian reported no relevant financial relationships.

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

An experimental antiviral pill appears to work very well at keeping people who are at high risk of severe COVID-19 from being admitted to the hospital and dying, according to the drug’s maker, Pfizer.

The drug -- called Paxlovid -- was 89% effective, compared to a placebo, at preventing hospitalization or death in patients with COVID-19 who were at high risk of severe complications. The company says it plans to ask the FDA to authorize the drug for emergency use.

The medication appears to work so well that Pfizer has stopped enrollment in the trial of the drug, which works by blocking an enzyme called a protease that the new coronavirus needs to make more copies of itself.

Stopping a clinical trial is a rare action that’s typically taken when a therapy appears to be very effective or clearly dangerous. In both those cases, it’s considered unethical to continue a clinical trial where people are randomly assigned either an active drug or a placebo, when safer or more effective options are available to them.

In this case, the company said in a news release that the move was recommended by an independent panel of advisers who are overseeing the trial, called a data safety monitoring committee, and done in consultation with the FDA.

“Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, PhD, Pfizer chairman and chief executive officer. “These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations.”

In a randomized clinical trial that included more than 1,900 patients who tested positive for COVID-19 and were at risk for having severe complications for their infections, those who received Paxlovid within 3 days of the start of their symptoms were 89% less likely to be hospitalized than those who got a placebo pill -- three patients out of 389 who got the drug were hospitalized, compared with 27 out of 385 who got the placebo. Among patients who got the drug within 5 days of the start of their symptoms, six out of 607 were hospitalized within 28 days, compared to 41 out of 612 who got the placebo.

There were no deaths over the course of a month in patients who took Paxlovid, but 10 deaths in the group that got the placebo.

The news comes on the heels of an announcement in October by the drug company Merck that its experimental antiviral pill, molnupiravir, reduced the risk of hospitalization or death by 50% in patients with mild to moderate COVID, compared to a placebo.

The United Kingdom became the first country to authorize the use of molnupiravir, which is brand-named Lagevrio.

Stephen Griffin, PhD, an associate professor of medicine at the University of Leeds, hailed the success of both new antiviral pills.

“They both demonstrate that, with appropriate investment, the development of bespoke direct-acting antiviral drugs targeting SARS-CoV2 was eminently feasible and has ultimately proven far more successful than repurposing other drugs with questionable antiviral effects,” said Dr. Griffin, who was not involved in the development of either drug.

“The success of these antivirals potentially marks a new era in our ability to prevent the severe consequences of SARS-CoV2 infection, and is also a vital element for the care of clinically vulnerable people who may be unable to either receive or respond to vaccines,” he said.

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

An experimental antiviral pill appears to work very well at keeping people who are at high risk of severe COVID-19 from being admitted to the hospital and dying, according to the drug’s maker, Pfizer.

The drug -- called Paxlovid -- was 89% effective, compared to a placebo, at preventing hospitalization or death in patients with COVID-19 who were at high risk of severe complications. The company says it plans to ask the FDA to authorize the drug for emergency use.

The medication appears to work so well that Pfizer has stopped enrollment in the trial of the drug, which works by blocking an enzyme called a protease that the new coronavirus needs to make more copies of itself.

Stopping a clinical trial is a rare action that’s typically taken when a therapy appears to be very effective or clearly dangerous. In both those cases, it’s considered unethical to continue a clinical trial where people are randomly assigned either an active drug or a placebo, when safer or more effective options are available to them.

In this case, the company said in a news release that the move was recommended by an independent panel of advisers who are overseeing the trial, called a data safety monitoring committee, and done in consultation with the FDA.

“Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, PhD, Pfizer chairman and chief executive officer. “These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations.”

In a randomized clinical trial that included more than 1,900 patients who tested positive for COVID-19 and were at risk for having severe complications for their infections, those who received Paxlovid within 3 days of the start of their symptoms were 89% less likely to be hospitalized than those who got a placebo pill -- three patients out of 389 who got the drug were hospitalized, compared with 27 out of 385 who got the placebo. Among patients who got the drug within 5 days of the start of their symptoms, six out of 607 were hospitalized within 28 days, compared to 41 out of 612 who got the placebo.

There were no deaths over the course of a month in patients who took Paxlovid, but 10 deaths in the group that got the placebo.

The news comes on the heels of an announcement in October by the drug company Merck that its experimental antiviral pill, molnupiravir, reduced the risk of hospitalization or death by 50% in patients with mild to moderate COVID, compared to a placebo.

The United Kingdom became the first country to authorize the use of molnupiravir, which is brand-named Lagevrio.

Stephen Griffin, PhD, an associate professor of medicine at the University of Leeds, hailed the success of both new antiviral pills.

“They both demonstrate that, with appropriate investment, the development of bespoke direct-acting antiviral drugs targeting SARS-CoV2 was eminently feasible and has ultimately proven far more successful than repurposing other drugs with questionable antiviral effects,” said Dr. Griffin, who was not involved in the development of either drug.

“The success of these antivirals potentially marks a new era in our ability to prevent the severe consequences of SARS-CoV2 infection, and is also a vital element for the care of clinically vulnerable people who may be unable to either receive or respond to vaccines,” he said.

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

An experimental antiviral pill appears to work very well at keeping people who are at high risk of severe COVID-19 from being admitted to the hospital and dying, according to the drug’s maker, Pfizer.

The drug -- called Paxlovid -- was 89% effective, compared to a placebo, at preventing hospitalization or death in patients with COVID-19 who were at high risk of severe complications. The company says it plans to ask the FDA to authorize the drug for emergency use.

The medication appears to work so well that Pfizer has stopped enrollment in the trial of the drug, which works by blocking an enzyme called a protease that the new coronavirus needs to make more copies of itself.

Stopping a clinical trial is a rare action that’s typically taken when a therapy appears to be very effective or clearly dangerous. In both those cases, it’s considered unethical to continue a clinical trial where people are randomly assigned either an active drug or a placebo, when safer or more effective options are available to them.

In this case, the company said in a news release that the move was recommended by an independent panel of advisers who are overseeing the trial, called a data safety monitoring committee, and done in consultation with the FDA.

“Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, PhD, Pfizer chairman and chief executive officer. “These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations.”

In a randomized clinical trial that included more than 1,900 patients who tested positive for COVID-19 and were at risk for having severe complications for their infections, those who received Paxlovid within 3 days of the start of their symptoms were 89% less likely to be hospitalized than those who got a placebo pill -- three patients out of 389 who got the drug were hospitalized, compared with 27 out of 385 who got the placebo. Among patients who got the drug within 5 days of the start of their symptoms, six out of 607 were hospitalized within 28 days, compared to 41 out of 612 who got the placebo.

There were no deaths over the course of a month in patients who took Paxlovid, but 10 deaths in the group that got the placebo.

The news comes on the heels of an announcement in October by the drug company Merck that its experimental antiviral pill, molnupiravir, reduced the risk of hospitalization or death by 50% in patients with mild to moderate COVID, compared to a placebo.

The United Kingdom became the first country to authorize the use of molnupiravir, which is brand-named Lagevrio.

Stephen Griffin, PhD, an associate professor of medicine at the University of Leeds, hailed the success of both new antiviral pills.

“They both demonstrate that, with appropriate investment, the development of bespoke direct-acting antiviral drugs targeting SARS-CoV2 was eminently feasible and has ultimately proven far more successful than repurposing other drugs with questionable antiviral effects,” said Dr. Griffin, who was not involved in the development of either drug.

“The success of these antivirals potentially marks a new era in our ability to prevent the severe consequences of SARS-CoV2 infection, and is also a vital element for the care of clinically vulnerable people who may be unable to either receive or respond to vaccines,” he said.

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

The applicability of the results of the ISCHEMIA trial to real-world clinical practice in the United States has been called into question by a new study showing that less than a third of U.S. patients with stable ischemic heart disease (IHD) who currently undergo intervention would meet the trial’s inclusion criteria.

The ISCHEMIA trial, first reported in 2019, showed that, for stable patients with moderate to severe ischemia, an invasive approach using percutaneous coronary intervention (PCI) did not significantly reduce major cardiovascular events after a median 3.2 years of follow-up, compared with a conservative medical strategy.

For the current study, a group of interventionalists analyzed contemporary U.S. data on patients undergoing PCI and found that a large proportion of patients receiving PCI for stable ischemic heart disease in the United States would not have met criteria of the ISCHEMIA trial population.

The study was published online Nov. 1 in JACC: Cardiovascular Interventions).  

“While ISCHEMIA was a very well-conducted trial, our results show that it only applies to about one-third of stable IHD patients undergoing intervention in U.S. clinical practice in the real world. In this group, while ISCHEMIA did not show a reduction in event rate in the intervention group, there was a reduction in symptoms,” lead author Saurav Chatterjee, MD, Long Island Jewish Medical Center, New York, told this news organization.

“But ISCHEMIA did not really answer the question for 67% of stable IHD in current U.S. practice. We may be abIe to defer PCI in these patients, but we don’t know that from the ISCHEMIA trial, as these patients were not included in the trial,” Chatterjee said.  

“There is some concern that people will accept the ISCHEMIA results as being universal, but we cannot apply these results to all stable IHD patients who currently undergo intervention,” he added. “We believe that patients who do not fall into the ISCHEMIA population need a nuanced individual approach, taking into account symptom burden and patient preferences.”

In the new report, Dr. Chatterjee and associates note that the applicability of the ISCHEMIA findings to contemporary practice has been questioned by some, because of the exclusion of a significant proportion of patients that are routinely considered for revascularization, both within and outside of the United States.

They point out that the ISCHEMIA trial recruited 16.5% of its participants from the United States, and the proportion of patients in contemporary U.S. practice that would have qualified for the trial is not clear.

They therefore examined the proportion of stable IHD patients meeting inclusion criteria for the ISCHEMIA trial in a U.S. nationwide PCI registry.

The researchers used data from the National Cardiovascular Data Registry (NCDR) CathPCI Registry, which includes patients undergoing PCI at 1,662 institutions and accounts for more than 90% of PCI-capable hospitals in the United States.

All PCI procedures performed at institutions participating in the NCDR CathPCI Registry from October 2017 to June 2019 were identified. Patients presenting with acute coronary syndrome (ACS), cardiogenic shock, or cardiac arrest were excluded, as there is significant evidence in favor of revascularization in these groups, and they were not included in the ISCHEMIA trial.

Subsequently, all remaining stable IHD patients were classified into one of four groups.

• ISCHEMIA-like: These patients had intermediate- or high-risk findings on a stress test but no high-risk features that would have excluded enrollment into the ISCHEMIA trial
• High risk: This group comprised patients with stable IHD and left ventricular ejection fraction less than 35%, significant unprotected left main stenosis (>50%), preexisting dialysis, recent heart-failure exacerbation, or heart transplant. These patients would have met exclusion criteria for the ISCHEMIA trial
• Low risk: This group included patients with stable and negative or low-risk findings on stress test and would have met exclusion criteria for the ISCHEMIA trial
• Not classifiable: This group comprised patients with stable IHD not fitting any of the other cohorts, including no stress test or extent of ischemia not reported on stress testing. These patients would have not had enough information to clearly meet inclusion or exclusion criteria for the ISCHEMIA trial

Results showed that during the study period 927,011 patients underwent PCI as recorded in the NCDR CathPCI Registry. Of these, 58% had ACS, cardiogenic shock, or cardiac arrest and were excluded; the remaining 388,212 patients who underwent PCI for stable IHD comprised the study population.

Of these, 125,302 (32.28%) had a moderate- or high-risk stress test without high-risk anatomic or clinical features and met ISCHEMIA trial inclusion criteria.

Among stable IHD patients not meeting ISCHEMIA trial inclusion criteria, 71,852 (18.51%) had high-risk criteria that would have excluded them from the ISCHEMIA trial, a total of 67,159 (17.29%) patients had low-risk criteria that would have excluded them from the ISCHEMIA trial, and 123,899 (31.92%) were unclassifiable, either owing to lack of stress testing or the extent of ischemia not being reported on stress testing.

The authors suggest that the unclassifiable patients appear to represent a “higher-risk” population than those closely resembling the ISCHEMIA trial population, with more prior myocardial infarction and heart failure.
 

ISCHEMIA investigators respond

In an accompanying editorial, ISCHEMIA investigators David J. Maron, MD, Stanford (Calif.) University, and Sripal Bangalore, MD, and Judith S. Hochman, MD, New York University, argue that many of the patients highlighted by Dr. Chatterjee and associates were excluded from the ISCHEMIA trial for good reason.

They explain that ISCHEMIA was designed under the premise that prior stable IHD strategy trials such as COURAGE and BARI 2D included lower-risk patients, and the remaining gap was to evaluate the utility of invasive management in those at higher risk with moderate or severe stress-induced ischemia.

They point out that, among the NCDR patients with stable IHD in the current study by Dr. Chatterjee and associates who did not meet ISCHEMIA entry criteria, 18.5% had high-risk features, including 35.2% with left main coronary artery disease, 43.7% with left ventricular systolic dysfunction, and 16.8% with end-stage renal disease.

Although ISCHEMIA results do not apply to patients who were excluded from the trial, there is little controversy regarding the benefit of revascularization in patients with stable IHD with left main coronary artery disease or left ventricular ejection fraction <35%, which is why they were excluded from ISCHEMIA, the editorialists note.  

They also report that patients with end-stage renal disease, who were also designated as not meeting ISCHEMIA inclusion criteria, were included in the companion ISCHEMIA CKD trial.

They further point out that, at the other end of the risk spectrum, 17.3% of stable IHD patients in the current analysis had negative or low-risk functional testing, and these patients were excluded from ISCHEMIA because they were shown in COURAGE and BARI 2D to not benefit from revascularization, and they do not meet guideline recommendations for elective PCI in the absence of symptoms.

Of the 31.9% of stable IHD patients who had missing data on ischemic burden, the ISCHEMIA investigators say that some of these would have qualified for the trial, although it is not possible to say how many. They suggest a conservative estimate of 50%.

Taking these arguments into account, the editorialists recalculated the proportion of NCDR PCI patients with stable IHD who would have been included in ISCHEMIA as between 62.1% and 68.6% of patients.

They say the current NCDR analysis by Dr. Chatterjee and associates should be interpreted as indicating, at worst, that the ISCHEMIA trial results apply to only 32% of patients undergoing elective PCI in the United States, and at best “that the results apply to a far higher proportion, excluding only those at high risk (18.5%) or with unacceptable symptoms despite maximal medical therapy (percentage unknown), for whom PCI is clearly indicated.”

The editorialists conclude: “The purpose of the analysis by Chatterjee et al. is to inform the cardiovascular community of the proportion of patients with stable IHD in clinical practice who would have been excluded from ISCHEMIA without regard for the logic of each exclusion criterion. The purpose of this editorial is to provide context for the analysis, admittedly from the perspective of ISCHEMIA investigators, with the hope that this helps readers clearly see the relevance of the trial to patients under their care.”

They add: “For practical and ethical reasons, ISCHEMIA excluded stable patients with high-risk features, angina inadequately controlled by medication, and low-risk features who do not meet evidence-based guidelines for revascularization. That leaves a large percentage of patients for whom the ISCHEMIA trial is highly relevant; exactly what percentage on the basis of NCDR data is hard to say.”

The ISCHEMIA trial was supported by the National Heart, Lung, and Blood Institute.

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

The applicability of the results of the ISCHEMIA trial to real-world clinical practice in the United States has been called into question by a new study showing that less than a third of U.S. patients with stable ischemic heart disease (IHD) who currently undergo intervention would meet the trial’s inclusion criteria.

The ISCHEMIA trial, first reported in 2019, showed that, for stable patients with moderate to severe ischemia, an invasive approach using percutaneous coronary intervention (PCI) did not significantly reduce major cardiovascular events after a median 3.2 years of follow-up, compared with a conservative medical strategy.

For the current study, a group of interventionalists analyzed contemporary U.S. data on patients undergoing PCI and found that a large proportion of patients receiving PCI for stable ischemic heart disease in the United States would not have met criteria of the ISCHEMIA trial population.

The study was published online Nov. 1 in JACC: Cardiovascular Interventions).  

“While ISCHEMIA was a very well-conducted trial, our results show that it only applies to about one-third of stable IHD patients undergoing intervention in U.S. clinical practice in the real world. In this group, while ISCHEMIA did not show a reduction in event rate in the intervention group, there was a reduction in symptoms,” lead author Saurav Chatterjee, MD, Long Island Jewish Medical Center, New York, told this news organization.

“But ISCHEMIA did not really answer the question for 67% of stable IHD in current U.S. practice. We may be abIe to defer PCI in these patients, but we don’t know that from the ISCHEMIA trial, as these patients were not included in the trial,” Chatterjee said.  

“There is some concern that people will accept the ISCHEMIA results as being universal, but we cannot apply these results to all stable IHD patients who currently undergo intervention,” he added. “We believe that patients who do not fall into the ISCHEMIA population need a nuanced individual approach, taking into account symptom burden and patient preferences.”

In the new report, Dr. Chatterjee and associates note that the applicability of the ISCHEMIA findings to contemporary practice has been questioned by some, because of the exclusion of a significant proportion of patients that are routinely considered for revascularization, both within and outside of the United States.

They point out that the ISCHEMIA trial recruited 16.5% of its participants from the United States, and the proportion of patients in contemporary U.S. practice that would have qualified for the trial is not clear.

They therefore examined the proportion of stable IHD patients meeting inclusion criteria for the ISCHEMIA trial in a U.S. nationwide PCI registry.

The researchers used data from the National Cardiovascular Data Registry (NCDR) CathPCI Registry, which includes patients undergoing PCI at 1,662 institutions and accounts for more than 90% of PCI-capable hospitals in the United States.

All PCI procedures performed at institutions participating in the NCDR CathPCI Registry from October 2017 to June 2019 were identified. Patients presenting with acute coronary syndrome (ACS), cardiogenic shock, or cardiac arrest were excluded, as there is significant evidence in favor of revascularization in these groups, and they were not included in the ISCHEMIA trial.

Subsequently, all remaining stable IHD patients were classified into one of four groups.

• ISCHEMIA-like: These patients had intermediate- or high-risk findings on a stress test but no high-risk features that would have excluded enrollment into the ISCHEMIA trial
• High risk: This group comprised patients with stable IHD and left ventricular ejection fraction less than 35%, significant unprotected left main stenosis (>50%), preexisting dialysis, recent heart-failure exacerbation, or heart transplant. These patients would have met exclusion criteria for the ISCHEMIA trial
• Low risk: This group included patients with stable and negative or low-risk findings on stress test and would have met exclusion criteria for the ISCHEMIA trial
• Not classifiable: This group comprised patients with stable IHD not fitting any of the other cohorts, including no stress test or extent of ischemia not reported on stress testing. These patients would have not had enough information to clearly meet inclusion or exclusion criteria for the ISCHEMIA trial

Results showed that during the study period 927,011 patients underwent PCI as recorded in the NCDR CathPCI Registry. Of these, 58% had ACS, cardiogenic shock, or cardiac arrest and were excluded; the remaining 388,212 patients who underwent PCI for stable IHD comprised the study population.

Of these, 125,302 (32.28%) had a moderate- or high-risk stress test without high-risk anatomic or clinical features and met ISCHEMIA trial inclusion criteria.

Among stable IHD patients not meeting ISCHEMIA trial inclusion criteria, 71,852 (18.51%) had high-risk criteria that would have excluded them from the ISCHEMIA trial, a total of 67,159 (17.29%) patients had low-risk criteria that would have excluded them from the ISCHEMIA trial, and 123,899 (31.92%) were unclassifiable, either owing to lack of stress testing or the extent of ischemia not being reported on stress testing.

The authors suggest that the unclassifiable patients appear to represent a “higher-risk” population than those closely resembling the ISCHEMIA trial population, with more prior myocardial infarction and heart failure.
 

ISCHEMIA investigators respond

In an accompanying editorial, ISCHEMIA investigators David J. Maron, MD, Stanford (Calif.) University, and Sripal Bangalore, MD, and Judith S. Hochman, MD, New York University, argue that many of the patients highlighted by Dr. Chatterjee and associates were excluded from the ISCHEMIA trial for good reason.

They explain that ISCHEMIA was designed under the premise that prior stable IHD strategy trials such as COURAGE and BARI 2D included lower-risk patients, and the remaining gap was to evaluate the utility of invasive management in those at higher risk with moderate or severe stress-induced ischemia.

They point out that, among the NCDR patients with stable IHD in the current study by Dr. Chatterjee and associates who did not meet ISCHEMIA entry criteria, 18.5% had high-risk features, including 35.2% with left main coronary artery disease, 43.7% with left ventricular systolic dysfunction, and 16.8% with end-stage renal disease.

Although ISCHEMIA results do not apply to patients who were excluded from the trial, there is little controversy regarding the benefit of revascularization in patients with stable IHD with left main coronary artery disease or left ventricular ejection fraction <35%, which is why they were excluded from ISCHEMIA, the editorialists note.  

They also report that patients with end-stage renal disease, who were also designated as not meeting ISCHEMIA inclusion criteria, were included in the companion ISCHEMIA CKD trial.

They further point out that, at the other end of the risk spectrum, 17.3% of stable IHD patients in the current analysis had negative or low-risk functional testing, and these patients were excluded from ISCHEMIA because they were shown in COURAGE and BARI 2D to not benefit from revascularization, and they do not meet guideline recommendations for elective PCI in the absence of symptoms.

Of the 31.9% of stable IHD patients who had missing data on ischemic burden, the ISCHEMIA investigators say that some of these would have qualified for the trial, although it is not possible to say how many. They suggest a conservative estimate of 50%.

Taking these arguments into account, the editorialists recalculated the proportion of NCDR PCI patients with stable IHD who would have been included in ISCHEMIA as between 62.1% and 68.6% of patients.

They say the current NCDR analysis by Dr. Chatterjee and associates should be interpreted as indicating, at worst, that the ISCHEMIA trial results apply to only 32% of patients undergoing elective PCI in the United States, and at best “that the results apply to a far higher proportion, excluding only those at high risk (18.5%) or with unacceptable symptoms despite maximal medical therapy (percentage unknown), for whom PCI is clearly indicated.”

The editorialists conclude: “The purpose of the analysis by Chatterjee et al. is to inform the cardiovascular community of the proportion of patients with stable IHD in clinical practice who would have been excluded from ISCHEMIA without regard for the logic of each exclusion criterion. The purpose of this editorial is to provide context for the analysis, admittedly from the perspective of ISCHEMIA investigators, with the hope that this helps readers clearly see the relevance of the trial to patients under their care.”

They add: “For practical and ethical reasons, ISCHEMIA excluded stable patients with high-risk features, angina inadequately controlled by medication, and low-risk features who do not meet evidence-based guidelines for revascularization. That leaves a large percentage of patients for whom the ISCHEMIA trial is highly relevant; exactly what percentage on the basis of NCDR data is hard to say.”

The ISCHEMIA trial was supported by the National Heart, Lung, and Blood Institute.

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

The applicability of the results of the ISCHEMIA trial to real-world clinical practice in the United States has been called into question by a new study showing that less than a third of U.S. patients with stable ischemic heart disease (IHD) who currently undergo intervention would meet the trial’s inclusion criteria.

The ISCHEMIA trial, first reported in 2019, showed that, for stable patients with moderate to severe ischemia, an invasive approach using percutaneous coronary intervention (PCI) did not significantly reduce major cardiovascular events after a median 3.2 years of follow-up, compared with a conservative medical strategy.

For the current study, a group of interventionalists analyzed contemporary U.S. data on patients undergoing PCI and found that a large proportion of patients receiving PCI for stable ischemic heart disease in the United States would not have met criteria of the ISCHEMIA trial population.

The study was published online Nov. 1 in JACC: Cardiovascular Interventions).  

“While ISCHEMIA was a very well-conducted trial, our results show that it only applies to about one-third of stable IHD patients undergoing intervention in U.S. clinical practice in the real world. In this group, while ISCHEMIA did not show a reduction in event rate in the intervention group, there was a reduction in symptoms,” lead author Saurav Chatterjee, MD, Long Island Jewish Medical Center, New York, told this news organization.

“But ISCHEMIA did not really answer the question for 67% of stable IHD in current U.S. practice. We may be abIe to defer PCI in these patients, but we don’t know that from the ISCHEMIA trial, as these patients were not included in the trial,” Chatterjee said.  

“There is some concern that people will accept the ISCHEMIA results as being universal, but we cannot apply these results to all stable IHD patients who currently undergo intervention,” he added. “We believe that patients who do not fall into the ISCHEMIA population need a nuanced individual approach, taking into account symptom burden and patient preferences.”

In the new report, Dr. Chatterjee and associates note that the applicability of the ISCHEMIA findings to contemporary practice has been questioned by some, because of the exclusion of a significant proportion of patients that are routinely considered for revascularization, both within and outside of the United States.

They point out that the ISCHEMIA trial recruited 16.5% of its participants from the United States, and the proportion of patients in contemporary U.S. practice that would have qualified for the trial is not clear.

They therefore examined the proportion of stable IHD patients meeting inclusion criteria for the ISCHEMIA trial in a U.S. nationwide PCI registry.

The researchers used data from the National Cardiovascular Data Registry (NCDR) CathPCI Registry, which includes patients undergoing PCI at 1,662 institutions and accounts for more than 90% of PCI-capable hospitals in the United States.

All PCI procedures performed at institutions participating in the NCDR CathPCI Registry from October 2017 to June 2019 were identified. Patients presenting with acute coronary syndrome (ACS), cardiogenic shock, or cardiac arrest were excluded, as there is significant evidence in favor of revascularization in these groups, and they were not included in the ISCHEMIA trial.

Subsequently, all remaining stable IHD patients were classified into one of four groups.

• ISCHEMIA-like: These patients had intermediate- or high-risk findings on a stress test but no high-risk features that would have excluded enrollment into the ISCHEMIA trial
• High risk: This group comprised patients with stable IHD and left ventricular ejection fraction less than 35%, significant unprotected left main stenosis (>50%), preexisting dialysis, recent heart-failure exacerbation, or heart transplant. These patients would have met exclusion criteria for the ISCHEMIA trial
• Low risk: This group included patients with stable and negative or low-risk findings on stress test and would have met exclusion criteria for the ISCHEMIA trial
• Not classifiable: This group comprised patients with stable IHD not fitting any of the other cohorts, including no stress test or extent of ischemia not reported on stress testing. These patients would have not had enough information to clearly meet inclusion or exclusion criteria for the ISCHEMIA trial

Results showed that during the study period 927,011 patients underwent PCI as recorded in the NCDR CathPCI Registry. Of these, 58% had ACS, cardiogenic shock, or cardiac arrest and were excluded; the remaining 388,212 patients who underwent PCI for stable IHD comprised the study population.

Of these, 125,302 (32.28%) had a moderate- or high-risk stress test without high-risk anatomic or clinical features and met ISCHEMIA trial inclusion criteria.

Among stable IHD patients not meeting ISCHEMIA trial inclusion criteria, 71,852 (18.51%) had high-risk criteria that would have excluded them from the ISCHEMIA trial, a total of 67,159 (17.29%) patients had low-risk criteria that would have excluded them from the ISCHEMIA trial, and 123,899 (31.92%) were unclassifiable, either owing to lack of stress testing or the extent of ischemia not being reported on stress testing.

The authors suggest that the unclassifiable patients appear to represent a “higher-risk” population than those closely resembling the ISCHEMIA trial population, with more prior myocardial infarction and heart failure.
 

ISCHEMIA investigators respond

In an accompanying editorial, ISCHEMIA investigators David J. Maron, MD, Stanford (Calif.) University, and Sripal Bangalore, MD, and Judith S. Hochman, MD, New York University, argue that many of the patients highlighted by Dr. Chatterjee and associates were excluded from the ISCHEMIA trial for good reason.

They explain that ISCHEMIA was designed under the premise that prior stable IHD strategy trials such as COURAGE and BARI 2D included lower-risk patients, and the remaining gap was to evaluate the utility of invasive management in those at higher risk with moderate or severe stress-induced ischemia.

They point out that, among the NCDR patients with stable IHD in the current study by Dr. Chatterjee and associates who did not meet ISCHEMIA entry criteria, 18.5% had high-risk features, including 35.2% with left main coronary artery disease, 43.7% with left ventricular systolic dysfunction, and 16.8% with end-stage renal disease.

Although ISCHEMIA results do not apply to patients who were excluded from the trial, there is little controversy regarding the benefit of revascularization in patients with stable IHD with left main coronary artery disease or left ventricular ejection fraction <35%, which is why they were excluded from ISCHEMIA, the editorialists note.  

They also report that patients with end-stage renal disease, who were also designated as not meeting ISCHEMIA inclusion criteria, were included in the companion ISCHEMIA CKD trial.

They further point out that, at the other end of the risk spectrum, 17.3% of stable IHD patients in the current analysis had negative or low-risk functional testing, and these patients were excluded from ISCHEMIA because they were shown in COURAGE and BARI 2D to not benefit from revascularization, and they do not meet guideline recommendations for elective PCI in the absence of symptoms.

Of the 31.9% of stable IHD patients who had missing data on ischemic burden, the ISCHEMIA investigators say that some of these would have qualified for the trial, although it is not possible to say how many. They suggest a conservative estimate of 50%.

Taking these arguments into account, the editorialists recalculated the proportion of NCDR PCI patients with stable IHD who would have been included in ISCHEMIA as between 62.1% and 68.6% of patients.

They say the current NCDR analysis by Dr. Chatterjee and associates should be interpreted as indicating, at worst, that the ISCHEMIA trial results apply to only 32% of patients undergoing elective PCI in the United States, and at best “that the results apply to a far higher proportion, excluding only those at high risk (18.5%) or with unacceptable symptoms despite maximal medical therapy (percentage unknown), for whom PCI is clearly indicated.”

The editorialists conclude: “The purpose of the analysis by Chatterjee et al. is to inform the cardiovascular community of the proportion of patients with stable IHD in clinical practice who would have been excluded from ISCHEMIA without regard for the logic of each exclusion criterion. The purpose of this editorial is to provide context for the analysis, admittedly from the perspective of ISCHEMIA investigators, with the hope that this helps readers clearly see the relevance of the trial to patients under their care.”

They add: “For practical and ethical reasons, ISCHEMIA excluded stable patients with high-risk features, angina inadequately controlled by medication, and low-risk features who do not meet evidence-based guidelines for revascularization. That leaves a large percentage of patients for whom the ISCHEMIA trial is highly relevant; exactly what percentage on the basis of NCDR data is hard to say.”

The ISCHEMIA trial was supported by the National Heart, Lung, and Blood Institute.

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