Heart Failure

While the investigation into cases of myocarditis possibly associated with COVID vaccines proceeds, the American Heart Association/American Stroke Association (ASA) continue to urge everyone who is eligible for the vaccine to get it without delay.

“We remain confident that the benefits of vaccination far exceed the very unusual risks,” the leadership of the AHA/ASA said in a statement issued June 12.

“The risks of COVID-19 infection include its potentially fatal consequences and the potential long-term health effects that are still revealing themselves, including lingering consequences affecting the heart, brain, vascular system, and other organs after infection,” they point out.

Late last week, the Centers for Disease Control and Prevention alerted health care providers that the COVID-19 Vaccine Safety Technical Work Group (VaST) of the Advisory Committee on Immunization Practices (ACIP) will meet June 18 to review cases of myocarditis reported in adolescents and young adults after they received a COVID-19 vaccine manufactured by Pfizer-BioNTech or Moderna.

The CDC is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

These cases may occur more often in males than females and more frequently after the second dose than the first dose of either mRNA vaccine. Symptoms typically occur in the 3 days after administration.

“The CDC’s ongoing investigation into cases of suspected myocarditis reflects a strong and steadfast commitment to transparency and the importance of scientific rigor on all fronts. We applaud the CDC’s unwavering efforts to lead our nation’s scientific and public health efforts, including ensuring the continued safety of the COVID-19 vaccines,” the AHA/ASA states.

They emphasize that vaccinations should continue, and say it’s important to consider the details of the suspected myocarditis cases being investigated by the CDC.

As of June 11, more than 306 million doses of COVID-19 vaccines have been administered in the United States (since Dec. 14, 2020) and nearly 43% of Americans – more than 142 million people – are now fully vaccinated.

According to the June 10 CDC VAERS report detailing adverse events through May 31:

• 789 cases of suspected myocarditis have been reported, with 475 involving people younger than 30 years; 79 cases reported were in patients 16 or 17 years old.
• The vast majority (81%) of the 270 patients younger than 30 years who were discharged from care after suspected myocarditis related to COVID-19 vaccination have recovered fully; the remaining 19% of patients report ongoing symptoms or complete data are missing.
• 196 cases of suspected myocarditis after a COVID-19 vaccine were reported in young adults 18 to 24 years of age, which is higher than expected for this age group.

As of May 31, only about 9% of the COVID-19 vaccine doses administered were to people 16 to 24 years of age, which is why this “higher-than-normal rate of possible myocarditis cases” warrants investigation, the AHA/ASA says.

They note that these suspected myocarditis cases were reported to VAERS because of their proximity to COVID-19 vaccine administration.

It remains to be determined which cases meet the clinical criteria for a diagnosis of myocarditis and whether they have any direct connection to the COVID-19 vaccine, the AHA/ASA says.

They urge all health care professionals to be aware of “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation.

They advise asking patients who present with symptoms related to these conditions about the timing of recent COVID vaccinations, as needed, to confirm the diagnosis and provide appropriate treatment quickly.

The AHA will be at the CDC’s June 18 meeting to review the latest evidence on cases of suspected myocarditis after the COVID-19 vaccine, the statement adds.

The statement notes that it reflects the views of the AHA/ASA and its scientific leadership, including current president Mitchel S.V. Elkind, MD, PhD; immediate past-president Robert A. Harrington, MD; president-elect Donald M. Lloyd-Jones, MD; AHA/ASA chief science and medical officer Mariell Jessup, MD; and chief medical officer for prevention Eduardo Sanchez, MD, MPH.

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

While the investigation into cases of myocarditis possibly associated with COVID vaccines proceeds, the American Heart Association/American Stroke Association (ASA) continue to urge everyone who is eligible for the vaccine to get it without delay.

“We remain confident that the benefits of vaccination far exceed the very unusual risks,” the leadership of the AHA/ASA said in a statement issued June 12.

“The risks of COVID-19 infection include its potentially fatal consequences and the potential long-term health effects that are still revealing themselves, including lingering consequences affecting the heart, brain, vascular system, and other organs after infection,” they point out.

Late last week, the Centers for Disease Control and Prevention alerted health care providers that the COVID-19 Vaccine Safety Technical Work Group (VaST) of the Advisory Committee on Immunization Practices (ACIP) will meet June 18 to review cases of myocarditis reported in adolescents and young adults after they received a COVID-19 vaccine manufactured by Pfizer-BioNTech or Moderna.

The CDC is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

These cases may occur more often in males than females and more frequently after the second dose than the first dose of either mRNA vaccine. Symptoms typically occur in the 3 days after administration.

“The CDC’s ongoing investigation into cases of suspected myocarditis reflects a strong and steadfast commitment to transparency and the importance of scientific rigor on all fronts. We applaud the CDC’s unwavering efforts to lead our nation’s scientific and public health efforts, including ensuring the continued safety of the COVID-19 vaccines,” the AHA/ASA states.

They emphasize that vaccinations should continue, and say it’s important to consider the details of the suspected myocarditis cases being investigated by the CDC.

As of June 11, more than 306 million doses of COVID-19 vaccines have been administered in the United States (since Dec. 14, 2020) and nearly 43% of Americans – more than 142 million people – are now fully vaccinated.

According to the June 10 CDC VAERS report detailing adverse events through May 31:

• 789 cases of suspected myocarditis have been reported, with 475 involving people younger than 30 years; 79 cases reported were in patients 16 or 17 years old.
• The vast majority (81%) of the 270 patients younger than 30 years who were discharged from care after suspected myocarditis related to COVID-19 vaccination have recovered fully; the remaining 19% of patients report ongoing symptoms or complete data are missing.
• 196 cases of suspected myocarditis after a COVID-19 vaccine were reported in young adults 18 to 24 years of age, which is higher than expected for this age group.

As of May 31, only about 9% of the COVID-19 vaccine doses administered were to people 16 to 24 years of age, which is why this “higher-than-normal rate of possible myocarditis cases” warrants investigation, the AHA/ASA says.

They note that these suspected myocarditis cases were reported to VAERS because of their proximity to COVID-19 vaccine administration.

It remains to be determined which cases meet the clinical criteria for a diagnosis of myocarditis and whether they have any direct connection to the COVID-19 vaccine, the AHA/ASA says.

They urge all health care professionals to be aware of “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation.

They advise asking patients who present with symptoms related to these conditions about the timing of recent COVID vaccinations, as needed, to confirm the diagnosis and provide appropriate treatment quickly.

The AHA will be at the CDC’s June 18 meeting to review the latest evidence on cases of suspected myocarditis after the COVID-19 vaccine, the statement adds.

The statement notes that it reflects the views of the AHA/ASA and its scientific leadership, including current president Mitchel S.V. Elkind, MD, PhD; immediate past-president Robert A. Harrington, MD; president-elect Donald M. Lloyd-Jones, MD; AHA/ASA chief science and medical officer Mariell Jessup, MD; and chief medical officer for prevention Eduardo Sanchez, MD, MPH.

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

While the investigation into cases of myocarditis possibly associated with COVID vaccines proceeds, the American Heart Association/American Stroke Association (ASA) continue to urge everyone who is eligible for the vaccine to get it without delay.

“We remain confident that the benefits of vaccination far exceed the very unusual risks,” the leadership of the AHA/ASA said in a statement issued June 12.

“The risks of COVID-19 infection include its potentially fatal consequences and the potential long-term health effects that are still revealing themselves, including lingering consequences affecting the heart, brain, vascular system, and other organs after infection,” they point out.

Late last week, the Centers for Disease Control and Prevention alerted health care providers that the COVID-19 Vaccine Safety Technical Work Group (VaST) of the Advisory Committee on Immunization Practices (ACIP) will meet June 18 to review cases of myocarditis reported in adolescents and young adults after they received a COVID-19 vaccine manufactured by Pfizer-BioNTech or Moderna.

The CDC is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

These cases may occur more often in males than females and more frequently after the second dose than the first dose of either mRNA vaccine. Symptoms typically occur in the 3 days after administration.

“The CDC’s ongoing investigation into cases of suspected myocarditis reflects a strong and steadfast commitment to transparency and the importance of scientific rigor on all fronts. We applaud the CDC’s unwavering efforts to lead our nation’s scientific and public health efforts, including ensuring the continued safety of the COVID-19 vaccines,” the AHA/ASA states.

They emphasize that vaccinations should continue, and say it’s important to consider the details of the suspected myocarditis cases being investigated by the CDC.

As of June 11, more than 306 million doses of COVID-19 vaccines have been administered in the United States (since Dec. 14, 2020) and nearly 43% of Americans – more than 142 million people – are now fully vaccinated.

According to the June 10 CDC VAERS report detailing adverse events through May 31:

• 789 cases of suspected myocarditis have been reported, with 475 involving people younger than 30 years; 79 cases reported were in patients 16 or 17 years old.
• The vast majority (81%) of the 270 patients younger than 30 years who were discharged from care after suspected myocarditis related to COVID-19 vaccination have recovered fully; the remaining 19% of patients report ongoing symptoms or complete data are missing.
• 196 cases of suspected myocarditis after a COVID-19 vaccine were reported in young adults 18 to 24 years of age, which is higher than expected for this age group.

As of May 31, only about 9% of the COVID-19 vaccine doses administered were to people 16 to 24 years of age, which is why this “higher-than-normal rate of possible myocarditis cases” warrants investigation, the AHA/ASA says.

They note that these suspected myocarditis cases were reported to VAERS because of their proximity to COVID-19 vaccine administration.

It remains to be determined which cases meet the clinical criteria for a diagnosis of myocarditis and whether they have any direct connection to the COVID-19 vaccine, the AHA/ASA says.

They urge all health care professionals to be aware of “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation.

They advise asking patients who present with symptoms related to these conditions about the timing of recent COVID vaccinations, as needed, to confirm the diagnosis and provide appropriate treatment quickly.

The AHA will be at the CDC’s June 18 meeting to review the latest evidence on cases of suspected myocarditis after the COVID-19 vaccine, the statement adds.

The statement notes that it reflects the views of the AHA/ASA and its scientific leadership, including current president Mitchel S.V. Elkind, MD, PhD; immediate past-president Robert A. Harrington, MD; president-elect Donald M. Lloyd-Jones, MD; AHA/ASA chief science and medical officer Mariell Jessup, MD; and chief medical officer for prevention Eduardo Sanchez, MD, MPH.

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

Patients with obesity who had bariatric surgery had a lower risk of having a major adverse cardiovascular event (MACE) or dying from all causes during a median 7-year follow-up, compared with similar patients who did not undergo surgery.

These findings, from a province-wide retrospective cohort study from Quebec, follow two recent, slightly shorter similar trials.

Now we need a large randomized clinical trial (RCT), experts say, to definitively establish cardiovascular and mortality benefits in people with obesity who have metabolic/bariatric surgery. And such a trial is just beginning.

Philippe Bouchard, MD, a general surgery resident from McGill University in Montreal presented the Quebec study in a top papers session at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings showed that, among obese patients with metabolic syndrome, bariatric/metabolic surgery is associated with a sustained decrease in the incidence of MACE and all-cause mortality of at least 5 years, Dr. Bouchard said.

“The results of this population-based observational study should be validated in randomized controlled trials,” he concluded.

In the meantime, “we believe our study adds to the body of evidence in mainly two ways,” Dr. Bouchard told this news organization in an email.

It has a longer follow-up than recent observational studies, “a median of 7 years, compared to 3.9 years in a study from the Cleveland Clinic, and 4.6 years in one from Ontario, he said.

“This allows us to [estimate] an absolute risk reduction of MACE of 5.11% at 10 years,” he added. This is a smaller risk reduction than the roughly 40% risk reduction seen in the other two studies, possibly because of selection bias, Dr. Bouchard speculated.

“Second, most of the larger cohorts are heavily weighted on Roux-en-Y gastric bypass,” he continued. In contrast, their study included diverse procedures, including sleeve gastrectomy, duodenal switch, and adjustable gastric banding.

“Given the rise in popularity of a derivative of the duodenal switch – the single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADi-S) – we believe this information is timely and relevant to clinicians,” Dr. Bouchard said.
 

RCT on the subject is coming

“I totally agree that we need a large randomized controlled trial of bariatric surgery versus optimal medical therapy to conclusively establish” the impact of bariatric surgery on cardiovascular outcomes, said the assigned discussant, Mehran Anvari, MD. And their research group is just about to begin one.

In the absence of RCT data, clinicians “may currently not refer [eligible] patients for bariatric surgery because of the high risk they pose,” said Dr. Anvari, professor and director of the Centre for Minimal Access Surgery of McMaster University, Hamilton, Ont., and senior author in the Ontario study.

Furthermore, an important point is that the current trial extended the follow-up to 7 years, he told this news organization in an email.

That study included patients with diabetes and hypertension, he added, whereas his group included patients with a history of cardiovascular disease and/or heart failure.

“We hope these studies encourage general practitioners and cardiologists to consider bariatric surgery as a viable treatment option to prevent and reduce the risk of MACE in the obese patients [body mass index >35 kg/m²] with significant cardiovascular disease,” he said.

“We have embarked on a pilot RCT among bariatric centers of excellence in Ontario,” Dr. Anvari added, which showed the feasibility and safety of such a study.

He estimates that the RCT will need to recruit 2,000 patients to demonstrate the safety and effectiveness of bariatric surgery in reducing MACE and cardiac and all-cause mortality among patients with existing cardiovascular disease.

This “will require international collaboration,” he added, “and our group is currently establishing collaboration with sites in North America, Europe, and Australia to conduct such a study.”
 

Patients matched for age, sex, number of comorbidities

Quebec has a single public health care system that covers the cost of bariatric surgery for eligible patients; that is, those with a BMI greater than 35 kg/m² and comorbidities or a BMI greater than 40 kg/m².

Using this provincial health care database, which covers over 97% of the population, the researchers identified 3,637 patients with diabetes and/or hypertension who had bariatric surgery during 2007-2012.

They matched the surgery patients with 5,420 control patients with obesity who lived in the same geographic region and had a similar age, sex, and number of Charlson Comorbidity Index comorbidities, but did not undergo bariatric surgery.

The patients had a mean age of 50 and 64% were women.

Half had zero to one comorbidities, a quarter had two comorbidities, and another quarter had at least three comorbidities.

Most patients in the surgery group had type 2 diabetes (70%) and 50% had hypertension, whereas in the control group, most patients had hypertension (82%) and 41% had diabetes.

The most common type of bariatric surgery was adjustable gastric banding (42% of patients), followed by duodenal switch (24%), sleeve gastrectomy (23%), and Roux-en-Y gastric bypass (11%).

The primary outcome was the incidence of MACE, defined as coronary artery events (including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft), stroke, heart failure, and all-cause mortality,

After a median follow-up of 7-11 years, fewer patients in the surgical group than in the control group had MACE (20% vs. 25%) or died from all causes (4.1% vs. 6.3%, both statistically significant at P < .01)

Similarly, significantly fewer patients in the surgical group than in the control group had a coronary artery event or heart failure (each P < .01).

However, there were no significant between-group difference in the rate of stroke, possibly because of the small number of strokes.

The risk of MACE was 17% lower in the group that had bariatric surgery than in the control group (adjusted hazard ratio, 0.83; 95% confidence interval, 0.78-0.89), after adjusting for age, sex, and number of comorbidities.

In subgroup analysis, patients who had adjustable gastric banding, Roux-en-Y gastric bypass, or duodenal switch had a significantly lower risk of MACE than control patients.

The risk of MACE was similar in patients who had sleeve gastrectomy and in control patients.

However, these subgroup results need to be interpreted with caution since the surgery and control patients in each surgery type subgroup were not matched for age, sex, and comorbidities, said Dr. Bouchard.

He acknowledged that study limitations include a lack of information about the patients’ BMI, weight, medications, and glycemic control (hemoglobin A1c).

Dr. Bouchard and Dr. Anvari have no relevant financial disclosures.

Patients with obesity who had bariatric surgery had a lower risk of having a major adverse cardiovascular event (MACE) or dying from all causes during a median 7-year follow-up, compared with similar patients who did not undergo surgery.

These findings, from a province-wide retrospective cohort study from Quebec, follow two recent, slightly shorter similar trials.

Now we need a large randomized clinical trial (RCT), experts say, to definitively establish cardiovascular and mortality benefits in people with obesity who have metabolic/bariatric surgery. And such a trial is just beginning.

Philippe Bouchard, MD, a general surgery resident from McGill University in Montreal presented the Quebec study in a top papers session at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings showed that, among obese patients with metabolic syndrome, bariatric/metabolic surgery is associated with a sustained decrease in the incidence of MACE and all-cause mortality of at least 5 years, Dr. Bouchard said.

“The results of this population-based observational study should be validated in randomized controlled trials,” he concluded.

In the meantime, “we believe our study adds to the body of evidence in mainly two ways,” Dr. Bouchard told this news organization in an email.

It has a longer follow-up than recent observational studies, “a median of 7 years, compared to 3.9 years in a study from the Cleveland Clinic, and 4.6 years in one from Ontario, he said.

“This allows us to [estimate] an absolute risk reduction of MACE of 5.11% at 10 years,” he added. This is a smaller risk reduction than the roughly 40% risk reduction seen in the other two studies, possibly because of selection bias, Dr. Bouchard speculated.

“Second, most of the larger cohorts are heavily weighted on Roux-en-Y gastric bypass,” he continued. In contrast, their study included diverse procedures, including sleeve gastrectomy, duodenal switch, and adjustable gastric banding.

“Given the rise in popularity of a derivative of the duodenal switch – the single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADi-S) – we believe this information is timely and relevant to clinicians,” Dr. Bouchard said.
 

RCT on the subject is coming

“I totally agree that we need a large randomized controlled trial of bariatric surgery versus optimal medical therapy to conclusively establish” the impact of bariatric surgery on cardiovascular outcomes, said the assigned discussant, Mehran Anvari, MD. And their research group is just about to begin one.

In the absence of RCT data, clinicians “may currently not refer [eligible] patients for bariatric surgery because of the high risk they pose,” said Dr. Anvari, professor and director of the Centre for Minimal Access Surgery of McMaster University, Hamilton, Ont., and senior author in the Ontario study.

Furthermore, an important point is that the current trial extended the follow-up to 7 years, he told this news organization in an email.

That study included patients with diabetes and hypertension, he added, whereas his group included patients with a history of cardiovascular disease and/or heart failure.

“We hope these studies encourage general practitioners and cardiologists to consider bariatric surgery as a viable treatment option to prevent and reduce the risk of MACE in the obese patients [body mass index >35 kg/m²] with significant cardiovascular disease,” he said.

“We have embarked on a pilot RCT among bariatric centers of excellence in Ontario,” Dr. Anvari added, which showed the feasibility and safety of such a study.

He estimates that the RCT will need to recruit 2,000 patients to demonstrate the safety and effectiveness of bariatric surgery in reducing MACE and cardiac and all-cause mortality among patients with existing cardiovascular disease.

This “will require international collaboration,” he added, “and our group is currently establishing collaboration with sites in North America, Europe, and Australia to conduct such a study.”
 

Patients matched for age, sex, number of comorbidities

Quebec has a single public health care system that covers the cost of bariatric surgery for eligible patients; that is, those with a BMI greater than 35 kg/m² and comorbidities or a BMI greater than 40 kg/m².

Using this provincial health care database, which covers over 97% of the population, the researchers identified 3,637 patients with diabetes and/or hypertension who had bariatric surgery during 2007-2012.

They matched the surgery patients with 5,420 control patients with obesity who lived in the same geographic region and had a similar age, sex, and number of Charlson Comorbidity Index comorbidities, but did not undergo bariatric surgery.

The patients had a mean age of 50 and 64% were women.

Half had zero to one comorbidities, a quarter had two comorbidities, and another quarter had at least three comorbidities.

Most patients in the surgery group had type 2 diabetes (70%) and 50% had hypertension, whereas in the control group, most patients had hypertension (82%) and 41% had diabetes.

The most common type of bariatric surgery was adjustable gastric banding (42% of patients), followed by duodenal switch (24%), sleeve gastrectomy (23%), and Roux-en-Y gastric bypass (11%).

The primary outcome was the incidence of MACE, defined as coronary artery events (including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft), stroke, heart failure, and all-cause mortality,

After a median follow-up of 7-11 years, fewer patients in the surgical group than in the control group had MACE (20% vs. 25%) or died from all causes (4.1% vs. 6.3%, both statistically significant at P < .01)

Similarly, significantly fewer patients in the surgical group than in the control group had a coronary artery event or heart failure (each P < .01).

However, there were no significant between-group difference in the rate of stroke, possibly because of the small number of strokes.

The risk of MACE was 17% lower in the group that had bariatric surgery than in the control group (adjusted hazard ratio, 0.83; 95% confidence interval, 0.78-0.89), after adjusting for age, sex, and number of comorbidities.

In subgroup analysis, patients who had adjustable gastric banding, Roux-en-Y gastric bypass, or duodenal switch had a significantly lower risk of MACE than control patients.

The risk of MACE was similar in patients who had sleeve gastrectomy and in control patients.

However, these subgroup results need to be interpreted with caution since the surgery and control patients in each surgery type subgroup were not matched for age, sex, and comorbidities, said Dr. Bouchard.

He acknowledged that study limitations include a lack of information about the patients’ BMI, weight, medications, and glycemic control (hemoglobin A1c).

Dr. Bouchard and Dr. Anvari have no relevant financial disclosures.

Patients with obesity who had bariatric surgery had a lower risk of having a major adverse cardiovascular event (MACE) or dying from all causes during a median 7-year follow-up, compared with similar patients who did not undergo surgery.

These findings, from a province-wide retrospective cohort study from Quebec, follow two recent, slightly shorter similar trials.

Now we need a large randomized clinical trial (RCT), experts say, to definitively establish cardiovascular and mortality benefits in people with obesity who have metabolic/bariatric surgery. And such a trial is just beginning.

Philippe Bouchard, MD, a general surgery resident from McGill University in Montreal presented the Quebec study in a top papers session at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

The findings showed that, among obese patients with metabolic syndrome, bariatric/metabolic surgery is associated with a sustained decrease in the incidence of MACE and all-cause mortality of at least 5 years, Dr. Bouchard said.

“The results of this population-based observational study should be validated in randomized controlled trials,” he concluded.

In the meantime, “we believe our study adds to the body of evidence in mainly two ways,” Dr. Bouchard told this news organization in an email.

It has a longer follow-up than recent observational studies, “a median of 7 years, compared to 3.9 years in a study from the Cleveland Clinic, and 4.6 years in one from Ontario, he said.

“This allows us to [estimate] an absolute risk reduction of MACE of 5.11% at 10 years,” he added. This is a smaller risk reduction than the roughly 40% risk reduction seen in the other two studies, possibly because of selection bias, Dr. Bouchard speculated.

“Second, most of the larger cohorts are heavily weighted on Roux-en-Y gastric bypass,” he continued. In contrast, their study included diverse procedures, including sleeve gastrectomy, duodenal switch, and adjustable gastric banding.

“Given the rise in popularity of a derivative of the duodenal switch – the single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADi-S) – we believe this information is timely and relevant to clinicians,” Dr. Bouchard said.
 

RCT on the subject is coming

“I totally agree that we need a large randomized controlled trial of bariatric surgery versus optimal medical therapy to conclusively establish” the impact of bariatric surgery on cardiovascular outcomes, said the assigned discussant, Mehran Anvari, MD. And their research group is just about to begin one.

In the absence of RCT data, clinicians “may currently not refer [eligible] patients for bariatric surgery because of the high risk they pose,” said Dr. Anvari, professor and director of the Centre for Minimal Access Surgery of McMaster University, Hamilton, Ont., and senior author in the Ontario study.

Furthermore, an important point is that the current trial extended the follow-up to 7 years, he told this news organization in an email.

That study included patients with diabetes and hypertension, he added, whereas his group included patients with a history of cardiovascular disease and/or heart failure.

“We hope these studies encourage general practitioners and cardiologists to consider bariatric surgery as a viable treatment option to prevent and reduce the risk of MACE in the obese patients [body mass index >35 kg/m²] with significant cardiovascular disease,” he said.

“We have embarked on a pilot RCT among bariatric centers of excellence in Ontario,” Dr. Anvari added, which showed the feasibility and safety of such a study.

He estimates that the RCT will need to recruit 2,000 patients to demonstrate the safety and effectiveness of bariatric surgery in reducing MACE and cardiac and all-cause mortality among patients with existing cardiovascular disease.

This “will require international collaboration,” he added, “and our group is currently establishing collaboration with sites in North America, Europe, and Australia to conduct such a study.”
 

Patients matched for age, sex, number of comorbidities

Quebec has a single public health care system that covers the cost of bariatric surgery for eligible patients; that is, those with a BMI greater than 35 kg/m² and comorbidities or a BMI greater than 40 kg/m².

Using this provincial health care database, which covers over 97% of the population, the researchers identified 3,637 patients with diabetes and/or hypertension who had bariatric surgery during 2007-2012.

They matched the surgery patients with 5,420 control patients with obesity who lived in the same geographic region and had a similar age, sex, and number of Charlson Comorbidity Index comorbidities, but did not undergo bariatric surgery.

The patients had a mean age of 50 and 64% were women.

Half had zero to one comorbidities, a quarter had two comorbidities, and another quarter had at least three comorbidities.

Most patients in the surgery group had type 2 diabetes (70%) and 50% had hypertension, whereas in the control group, most patients had hypertension (82%) and 41% had diabetes.

The most common type of bariatric surgery was adjustable gastric banding (42% of patients), followed by duodenal switch (24%), sleeve gastrectomy (23%), and Roux-en-Y gastric bypass (11%).

The primary outcome was the incidence of MACE, defined as coronary artery events (including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft), stroke, heart failure, and all-cause mortality,

After a median follow-up of 7-11 years, fewer patients in the surgical group than in the control group had MACE (20% vs. 25%) or died from all causes (4.1% vs. 6.3%, both statistically significant at P < .01)

Similarly, significantly fewer patients in the surgical group than in the control group had a coronary artery event or heart failure (each P < .01).

However, there were no significant between-group difference in the rate of stroke, possibly because of the small number of strokes.

The risk of MACE was 17% lower in the group that had bariatric surgery than in the control group (adjusted hazard ratio, 0.83; 95% confidence interval, 0.78-0.89), after adjusting for age, sex, and number of comorbidities.

In subgroup analysis, patients who had adjustable gastric banding, Roux-en-Y gastric bypass, or duodenal switch had a significantly lower risk of MACE than control patients.

The risk of MACE was similar in patients who had sleeve gastrectomy and in control patients.

However, these subgroup results need to be interpreted with caution since the surgery and control patients in each surgery type subgroup were not matched for age, sex, and comorbidities, said Dr. Bouchard.

He acknowledged that study limitations include a lack of information about the patients’ BMI, weight, medications, and glycemic control (hemoglobin A1c).

Dr. Bouchard and Dr. Anvari have no relevant financial disclosures.

People with “metabolically healthy obesity” are actually not healthy, since they are at increased risk for several adverse cardiometabolic outcomes, compared with people without obesity and or adverse metabolic profiles, new research suggests.

The latest data on this controversial subject come from an analysis of nearly 400,000 people in the U.K. Biobank. Although the data also showed that metabolically healthy obesity poses less risk than “metabolically unhealthy” obesity, the risk of progression from healthy to unhealthy within 3-5 years was high.

“People with metabolically healthy obesity are not ‘healthy’ as they are at higher risk of atherosclerotic cardiovascular disease [ASCVD], heart failure, and respiratory diseases, compared with nonobese people with a normal metabolic profile. As such, weight management could be beneficial to all people with obesity irrespective of metabolic profile,” Ziyi Zhou and colleagues wrote in their report, published June 10, 2021, in Diabetologia.

Moreover, they advised avoiding the term metabolically healthy obesity entirely in clinical medicine “as it is misleading, and different strategies for risk stratification should be explored.”

In interviews, two experts provided somewhat different takes on the study and the overall subject.
 

‘Lifestyle should be explored with every single patient regardless of their weight’

Yoni Freedhoff, MD, medical director of the Bariatric Medical Institute, Ottawa, said “clinicians and patients need to be aware that obesity increases a person’s risk of various medical problems, and in turn this might lead to more frequent screening. This increased screening might be analogous to that of a person with a strong familial history of cancer who of course we would never describe as being ‘unhealthy’ as a consequence of their increased risk.”

In addition to screening, “lifestyle should be explored with every single patient regardless of their weight, and if a person’s weight is not affecting their health or their quality of life, a clinician need only let the patient know that, were they to want to discuss weight management options in the future, that they’d be there for them,” said Dr. Freedhoff.
 

‘Metabolically healthy obesity’ has had many definitions

Matthias Schulze, DrPH, head of the molecular epidemiology at the German Institute of Human Nutrition, Potsdam, and professor at the University of Potsdam, pointed out that the way metabolically healthy obesity is defined and the outcomes assessed make a difference.

In the current study, the term is defined as having a body mass index of at least 30 kg/m² and at least four of six metabolically healthy criteria: blood pressure, C-reactive protein, triacylglycerols, LDL cholesterol, HDL cholesterol, and hemoglobin A1c.

In May 2021, Dr. Schulze and associates reported in JAMA Network Open on a different definition that they found to identify individuals who do not have an increased risk of cardiovascular disease death and total mortality. Interestingly, they also used the U.K. Biobank as their validation cohort.

“We derived a new definition of metabolic health ... that is different from those used in [the current] article. Importantly, we included a measure of body fat distribution, waist-to-hip ratio. On the other side, we investigated only mortality outcomes and we can therefore not exclude the possibility that other outcomes may still be related. [For example], a higher diabetes risk may still be present among those we have defined as having metabolically healthy obesity.”

Dr. Schulze also said that several previous studies and meta-analyses have suggested that “previous common definitions of metabolically healthy obesity do not identify a subgroup without risk, or being at risk comparable to normal-weight metabolically healthy. Thus, this study confirms this conclusion. [But] this doesn’t rule out that there are better ways of defining subgroups.”

Clinically, he said “given that we investigated only mortality, we cannot conclude that our ‘metabolically healthy obesity’ group doesn’t require intervention.”

Higher rates of diabetes, ASCVD, heart failure, death

The current population-based study included 381,363 U.K. Biobank participants who were followed up for a median 11.2 years. Overall, about 55% did not have obesity or metabolic abnormalities, 9% had metabolically healthy obesity, 20% were metabolically unhealthy but did not have obesity, and 16% had metabolically unhealthy obesity as defined by the investigators.

The investigators adjusted the data for several potential confounders, including age, sex, ethnicity, education, socioeconomic status, smoking status, physical activity, and dietary factors.

Compared with individuals without obesity or metabolic abnormalities, those with metabolically healthy obesity had significantly higher rates of incident diabetes (hazard ratio, 4.32), ASCVD (HR, 1.18), myocardial infarction (HR, 1.23), stroke (HR, 1.10), heart failure (HR, 1.76), respiratory diseases (HR, 1.28), and chronic obstructive pulmonary disease (HR, 1.19).

In general, rates of cardiovascular and respiratory outcomes were highest in metabolically unhealthy obesity, followed by those without obesity but with metabolic abnormalities and those with metabolically healthy obesity. However, for incident and fatal heart failure and incident respiratory diseases, those with metabolically healthy obesity had higher rates than did those without obesity but with metabolic abnormalities.

Compared with those without obesity or metabolic abnormalities, those with metabolically healthy obesity had significantly higher all-cause mortality rates (HR, 1.22). And, compared with those without obesity (regardless of metabolic status) at baseline, those with metabolically healthy obesity were significantly more likely to have diabetes (HR, 2.06), heart failure (HR, 1.6), and respiratory diseases (HR, 1.2), but not ASCVD. The association was also significant for all-cause and heart failure mortality (HR, 1.12 and 1.44, respectively), but not for other causes of death.
 

Progression from metabolically healthy to unhealthy is common

Among 8,512 participants for whom longitudinal data were available for a median of 4.4 years, half of those with metabolically healthy obesity remained in that category, 20% no longer had obesity, and more than a quarter transitioned to metabolically unhealthy obesity. Compared with those without obesity or metabolic abnormalities throughout, those who transitioned from metabolically healthy to metabolically unhealthy had significantly higher rates of incident ASCVD (HR, 2.46) and all-cause mortality (HR, 3.07).

But those who remained in the metabolically healthy obesity category throughout did not have significantly increased risks for the adverse outcomes measured.

Ms. Zhou and colleagues noted that the data demonstrate heterogeneity among people with obesity, which offers the potential to stratify risk based on prognosis. For example, “people with [metabolically unhealthy obesity] were at a higher risk of mortality and morbidity than everyone else, and thus they should be prioritized for intervention.”

However, they add, “Obesity is associated with a wide range of diseases, and using a single label or categorical risk algorithm is unlikely to be effective compared with prediction algorithms based on disease-specific and continuous risk markers.”

Ms. Zhou has no disclosures. One coauthor has relationships with numerous pharmaceutical companies; the rest have none. Dr. Freedhoff has served as a director, officer, partner, employee, adviser, consultant, or trustee for the Bariatric Medical Institute and Constant Health. He is a speaker or a member of a speakers bureau for Obesity Canada and Novo Nordisk, received research grant from Novo Nordisk, and received income of at least $250 from WebMD, CTV, and Random House. Dr/ Schulze has received grants from German Federal Ministry of Education and Research.

People with “metabolically healthy obesity” are actually not healthy, since they are at increased risk for several adverse cardiometabolic outcomes, compared with people without obesity and or adverse metabolic profiles, new research suggests.

The latest data on this controversial subject come from an analysis of nearly 400,000 people in the U.K. Biobank. Although the data also showed that metabolically healthy obesity poses less risk than “metabolically unhealthy” obesity, the risk of progression from healthy to unhealthy within 3-5 years was high.

“People with metabolically healthy obesity are not ‘healthy’ as they are at higher risk of atherosclerotic cardiovascular disease [ASCVD], heart failure, and respiratory diseases, compared with nonobese people with a normal metabolic profile. As such, weight management could be beneficial to all people with obesity irrespective of metabolic profile,” Ziyi Zhou and colleagues wrote in their report, published June 10, 2021, in Diabetologia.

Moreover, they advised avoiding the term metabolically healthy obesity entirely in clinical medicine “as it is misleading, and different strategies for risk stratification should be explored.”

In interviews, two experts provided somewhat different takes on the study and the overall subject.
 

‘Lifestyle should be explored with every single patient regardless of their weight’

Yoni Freedhoff, MD, medical director of the Bariatric Medical Institute, Ottawa, said “clinicians and patients need to be aware that obesity increases a person’s risk of various medical problems, and in turn this might lead to more frequent screening. This increased screening might be analogous to that of a person with a strong familial history of cancer who of course we would never describe as being ‘unhealthy’ as a consequence of their increased risk.”

In addition to screening, “lifestyle should be explored with every single patient regardless of their weight, and if a person’s weight is not affecting their health or their quality of life, a clinician need only let the patient know that, were they to want to discuss weight management options in the future, that they’d be there for them,” said Dr. Freedhoff.
 

‘Metabolically healthy obesity’ has had many definitions

Matthias Schulze, DrPH, head of the molecular epidemiology at the German Institute of Human Nutrition, Potsdam, and professor at the University of Potsdam, pointed out that the way metabolically healthy obesity is defined and the outcomes assessed make a difference.

In the current study, the term is defined as having a body mass index of at least 30 kg/m² and at least four of six metabolically healthy criteria: blood pressure, C-reactive protein, triacylglycerols, LDL cholesterol, HDL cholesterol, and hemoglobin A1c.

In May 2021, Dr. Schulze and associates reported in JAMA Network Open on a different definition that they found to identify individuals who do not have an increased risk of cardiovascular disease death and total mortality. Interestingly, they also used the U.K. Biobank as their validation cohort.

“We derived a new definition of metabolic health ... that is different from those used in [the current] article. Importantly, we included a measure of body fat distribution, waist-to-hip ratio. On the other side, we investigated only mortality outcomes and we can therefore not exclude the possibility that other outcomes may still be related. [For example], a higher diabetes risk may still be present among those we have defined as having metabolically healthy obesity.”

Dr. Schulze also said that several previous studies and meta-analyses have suggested that “previous common definitions of metabolically healthy obesity do not identify a subgroup without risk, or being at risk comparable to normal-weight metabolically healthy. Thus, this study confirms this conclusion. [But] this doesn’t rule out that there are better ways of defining subgroups.”

Clinically, he said “given that we investigated only mortality, we cannot conclude that our ‘metabolically healthy obesity’ group doesn’t require intervention.”

Higher rates of diabetes, ASCVD, heart failure, death

The current population-based study included 381,363 U.K. Biobank participants who were followed up for a median 11.2 years. Overall, about 55% did not have obesity or metabolic abnormalities, 9% had metabolically healthy obesity, 20% were metabolically unhealthy but did not have obesity, and 16% had metabolically unhealthy obesity as defined by the investigators.

The investigators adjusted the data for several potential confounders, including age, sex, ethnicity, education, socioeconomic status, smoking status, physical activity, and dietary factors.

Compared with individuals without obesity or metabolic abnormalities, those with metabolically healthy obesity had significantly higher rates of incident diabetes (hazard ratio, 4.32), ASCVD (HR, 1.18), myocardial infarction (HR, 1.23), stroke (HR, 1.10), heart failure (HR, 1.76), respiratory diseases (HR, 1.28), and chronic obstructive pulmonary disease (HR, 1.19).

In general, rates of cardiovascular and respiratory outcomes were highest in metabolically unhealthy obesity, followed by those without obesity but with metabolic abnormalities and those with metabolically healthy obesity. However, for incident and fatal heart failure and incident respiratory diseases, those with metabolically healthy obesity had higher rates than did those without obesity but with metabolic abnormalities.

Compared with those without obesity or metabolic abnormalities, those with metabolically healthy obesity had significantly higher all-cause mortality rates (HR, 1.22). And, compared with those without obesity (regardless of metabolic status) at baseline, those with metabolically healthy obesity were significantly more likely to have diabetes (HR, 2.06), heart failure (HR, 1.6), and respiratory diseases (HR, 1.2), but not ASCVD. The association was also significant for all-cause and heart failure mortality (HR, 1.12 and 1.44, respectively), but not for other causes of death.
 

Progression from metabolically healthy to unhealthy is common

Among 8,512 participants for whom longitudinal data were available for a median of 4.4 years, half of those with metabolically healthy obesity remained in that category, 20% no longer had obesity, and more than a quarter transitioned to metabolically unhealthy obesity. Compared with those without obesity or metabolic abnormalities throughout, those who transitioned from metabolically healthy to metabolically unhealthy had significantly higher rates of incident ASCVD (HR, 2.46) and all-cause mortality (HR, 3.07).

But those who remained in the metabolically healthy obesity category throughout did not have significantly increased risks for the adverse outcomes measured.

Ms. Zhou and colleagues noted that the data demonstrate heterogeneity among people with obesity, which offers the potential to stratify risk based on prognosis. For example, “people with [metabolically unhealthy obesity] were at a higher risk of mortality and morbidity than everyone else, and thus they should be prioritized for intervention.”

However, they add, “Obesity is associated with a wide range of diseases, and using a single label or categorical risk algorithm is unlikely to be effective compared with prediction algorithms based on disease-specific and continuous risk markers.”

Ms. Zhou has no disclosures. One coauthor has relationships with numerous pharmaceutical companies; the rest have none. Dr. Freedhoff has served as a director, officer, partner, employee, adviser, consultant, or trustee for the Bariatric Medical Institute and Constant Health. He is a speaker or a member of a speakers bureau for Obesity Canada and Novo Nordisk, received research grant from Novo Nordisk, and received income of at least $250 from WebMD, CTV, and Random House. Dr/ Schulze has received grants from German Federal Ministry of Education and Research.

People with “metabolically healthy obesity” are actually not healthy, since they are at increased risk for several adverse cardiometabolic outcomes, compared with people without obesity and or adverse metabolic profiles, new research suggests.

The latest data on this controversial subject come from an analysis of nearly 400,000 people in the U.K. Biobank. Although the data also showed that metabolically healthy obesity poses less risk than “metabolically unhealthy” obesity, the risk of progression from healthy to unhealthy within 3-5 years was high.

“People with metabolically healthy obesity are not ‘healthy’ as they are at higher risk of atherosclerotic cardiovascular disease [ASCVD], heart failure, and respiratory diseases, compared with nonobese people with a normal metabolic profile. As such, weight management could be beneficial to all people with obesity irrespective of metabolic profile,” Ziyi Zhou and colleagues wrote in their report, published June 10, 2021, in Diabetologia.

Moreover, they advised avoiding the term metabolically healthy obesity entirely in clinical medicine “as it is misleading, and different strategies for risk stratification should be explored.”

In interviews, two experts provided somewhat different takes on the study and the overall subject.
 

‘Lifestyle should be explored with every single patient regardless of their weight’

Yoni Freedhoff, MD, medical director of the Bariatric Medical Institute, Ottawa, said “clinicians and patients need to be aware that obesity increases a person’s risk of various medical problems, and in turn this might lead to more frequent screening. This increased screening might be analogous to that of a person with a strong familial history of cancer who of course we would never describe as being ‘unhealthy’ as a consequence of their increased risk.”

In addition to screening, “lifestyle should be explored with every single patient regardless of their weight, and if a person’s weight is not affecting their health or their quality of life, a clinician need only let the patient know that, were they to want to discuss weight management options in the future, that they’d be there for them,” said Dr. Freedhoff.
 

‘Metabolically healthy obesity’ has had many definitions

Matthias Schulze, DrPH, head of the molecular epidemiology at the German Institute of Human Nutrition, Potsdam, and professor at the University of Potsdam, pointed out that the way metabolically healthy obesity is defined and the outcomes assessed make a difference.

In the current study, the term is defined as having a body mass index of at least 30 kg/m² and at least four of six metabolically healthy criteria: blood pressure, C-reactive protein, triacylglycerols, LDL cholesterol, HDL cholesterol, and hemoglobin A1c.

In May 2021, Dr. Schulze and associates reported in JAMA Network Open on a different definition that they found to identify individuals who do not have an increased risk of cardiovascular disease death and total mortality. Interestingly, they also used the U.K. Biobank as their validation cohort.

“We derived a new definition of metabolic health ... that is different from those used in [the current] article. Importantly, we included a measure of body fat distribution, waist-to-hip ratio. On the other side, we investigated only mortality outcomes and we can therefore not exclude the possibility that other outcomes may still be related. [For example], a higher diabetes risk may still be present among those we have defined as having metabolically healthy obesity.”

Dr. Schulze also said that several previous studies and meta-analyses have suggested that “previous common definitions of metabolically healthy obesity do not identify a subgroup without risk, or being at risk comparable to normal-weight metabolically healthy. Thus, this study confirms this conclusion. [But] this doesn’t rule out that there are better ways of defining subgroups.”

Clinically, he said “given that we investigated only mortality, we cannot conclude that our ‘metabolically healthy obesity’ group doesn’t require intervention.”

Higher rates of diabetes, ASCVD, heart failure, death

The current population-based study included 381,363 U.K. Biobank participants who were followed up for a median 11.2 years. Overall, about 55% did not have obesity or metabolic abnormalities, 9% had metabolically healthy obesity, 20% were metabolically unhealthy but did not have obesity, and 16% had metabolically unhealthy obesity as defined by the investigators.

The investigators adjusted the data for several potential confounders, including age, sex, ethnicity, education, socioeconomic status, smoking status, physical activity, and dietary factors.

Compared with individuals without obesity or metabolic abnormalities, those with metabolically healthy obesity had significantly higher rates of incident diabetes (hazard ratio, 4.32), ASCVD (HR, 1.18), myocardial infarction (HR, 1.23), stroke (HR, 1.10), heart failure (HR, 1.76), respiratory diseases (HR, 1.28), and chronic obstructive pulmonary disease (HR, 1.19).

In general, rates of cardiovascular and respiratory outcomes were highest in metabolically unhealthy obesity, followed by those without obesity but with metabolic abnormalities and those with metabolically healthy obesity. However, for incident and fatal heart failure and incident respiratory diseases, those with metabolically healthy obesity had higher rates than did those without obesity but with metabolic abnormalities.

Compared with those without obesity or metabolic abnormalities, those with metabolically healthy obesity had significantly higher all-cause mortality rates (HR, 1.22). And, compared with those without obesity (regardless of metabolic status) at baseline, those with metabolically healthy obesity were significantly more likely to have diabetes (HR, 2.06), heart failure (HR, 1.6), and respiratory diseases (HR, 1.2), but not ASCVD. The association was also significant for all-cause and heart failure mortality (HR, 1.12 and 1.44, respectively), but not for other causes of death.
 

Progression from metabolically healthy to unhealthy is common

Among 8,512 participants for whom longitudinal data were available for a median of 4.4 years, half of those with metabolically healthy obesity remained in that category, 20% no longer had obesity, and more than a quarter transitioned to metabolically unhealthy obesity. Compared with those without obesity or metabolic abnormalities throughout, those who transitioned from metabolically healthy to metabolically unhealthy had significantly higher rates of incident ASCVD (HR, 2.46) and all-cause mortality (HR, 3.07).

But those who remained in the metabolically healthy obesity category throughout did not have significantly increased risks for the adverse outcomes measured.

Ms. Zhou and colleagues noted that the data demonstrate heterogeneity among people with obesity, which offers the potential to stratify risk based on prognosis. For example, “people with [metabolically unhealthy obesity] were at a higher risk of mortality and morbidity than everyone else, and thus they should be prioritized for intervention.”

However, they add, “Obesity is associated with a wide range of diseases, and using a single label or categorical risk algorithm is unlikely to be effective compared with prediction algorithms based on disease-specific and continuous risk markers.”

Ms. Zhou has no disclosures. One coauthor has relationships with numerous pharmaceutical companies; the rest have none. Dr. Freedhoff has served as a director, officer, partner, employee, adviser, consultant, or trustee for the Bariatric Medical Institute and Constant Health. He is a speaker or a member of a speakers bureau for Obesity Canada and Novo Nordisk, received research grant from Novo Nordisk, and received income of at least $250 from WebMD, CTV, and Random House. Dr/ Schulze has received grants from German Federal Ministry of Education and Research.

Patients who underwent metabolic and bariatric surgery had fewer than half the number of hospitalizations for both acute and chronic episodes of heart failure with preserved ejection fraction (HFpEF) in a retrospective analysis of more than 2 million Americans collected in a national database.

In a multivariate analysis that adjusted for several variables patients without a history of bariatric surgery had three- to fivefold more hospitalizations for acute events involving HFpEF, and more than double the rate of hospitalizations for chronic HFpEF events, David R. Funes, MD, said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

While this analysis has the limitations of being retrospective, observational, and entirely reliant on procedure codes to define medical histories and outcomes, it had the advantage of using a large database designed to represent the U.S. adult population, said Dr. Funes, a bariatric surgeon at the Cleveland Clinic in Weston, Fla.
 

HFpEF effects could ‘extend’ surgery’s use

The report “adds an important article to the literature where there is a true void in trying to discern the effect of bariatric surgery on HFpEF,” commented Tammy L. Kindel, MD, PhD, director of the bariatric surgery program at the Medical College of Wisconsin, Milwaukee, and designated discussant for the report. “Minimal studies [up to now] demonstrate that weight loss in any form can modify diastolic dysfunction in patients with HFpEF. Studies that investigate the impact of bariatric surgery on clinical outcomes in patients with HFpEF are probably the most important for extending use of metabolic surgery,” Dr. Kindel said.

She added that “one of the most difficult parts of studying HFpEF” is making a firm diagnosis that often involves excluding other potential causes. She also questioned Dr. Funes about his confidence that his analysis correctly identified patients only with HFpEF. Dr. Funes replied that the diagnostic codes his team used allowed for a clear distinction between patients identified with HFpEF and those with heart failure with reduced ejection fraction, but he also admitted that his study’s complete reliance on these codes introduced a limitation to the analysis.
 

Including patients with diastolic dysfunction as well as HFpEF

The study used data collected during 2010-2015 by the National Inpatient Sample, run by the U.S. Department of Health & Human Services in a case-control analysis that included 296,041 patients who had undergone some form of bariatric surgery and 2,004,804 people with no history of bariatric surgery selected as controls on the basis of their obesity.

The absolute numbers showed that, during the observation period, the incidence of acute HFpEF hospitalizations was 0.19% among those with prior bariatric surgery and 0.86% among those with no surgery, and the incidence of chronic heart failure hospitalizations was 0.01% among people with prior bariatric surgery and 0.05% among those without prior surgery. Dr. Funes said. He noted that, during the period studied patients, with HFpEF were usually identified as having diastolic heart failure, an older name for the same disease.

In multivariate analyses that adjusted for age, sex, race, hypertension, diabetes, smoking, and coronary artery disease, people without prior bariatric surgery and with hypertension had a 2.8-fold increased rate of acute hospitalizations for HFpEF, while those without hypertension or prior bariatric surgery had a 5.2-fold increased rate. In addition, control patients, regardless of hypertension status, had a 2.9-fold increased rate of hospitalizations for chronic HFpEF events. All these differences were statistically significant.

Dr. Funes also reported results from additional analyses that focused on a roughly 68,000-patient subgroup of those included in the study who had a history of coronary artery disease, including about 62,000 with no prior bariatric surgery and nearly 6,000 people with prior bariatric surgery. In a multivariate analysis of this subgroup, people without prior bariatric surgery had a 2.65-fold increased rate of hospitalization for a HFpEF event (either acute or chronic), compared with those who had undergone bariatric surgery.

Dr. Funes and associates and Dr. Kindel had no relevant disclosures.

mzoler@mdedge.com

Patients who underwent metabolic and bariatric surgery had fewer than half the number of hospitalizations for both acute and chronic episodes of heart failure with preserved ejection fraction (HFpEF) in a retrospective analysis of more than 2 million Americans collected in a national database.

In a multivariate analysis that adjusted for several variables patients without a history of bariatric surgery had three- to fivefold more hospitalizations for acute events involving HFpEF, and more than double the rate of hospitalizations for chronic HFpEF events, David R. Funes, MD, said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

While this analysis has the limitations of being retrospective, observational, and entirely reliant on procedure codes to define medical histories and outcomes, it had the advantage of using a large database designed to represent the U.S. adult population, said Dr. Funes, a bariatric surgeon at the Cleveland Clinic in Weston, Fla.
 

HFpEF effects could ‘extend’ surgery’s use

The report “adds an important article to the literature where there is a true void in trying to discern the effect of bariatric surgery on HFpEF,” commented Tammy L. Kindel, MD, PhD, director of the bariatric surgery program at the Medical College of Wisconsin, Milwaukee, and designated discussant for the report. “Minimal studies [up to now] demonstrate that weight loss in any form can modify diastolic dysfunction in patients with HFpEF. Studies that investigate the impact of bariatric surgery on clinical outcomes in patients with HFpEF are probably the most important for extending use of metabolic surgery,” Dr. Kindel said.

She added that “one of the most difficult parts of studying HFpEF” is making a firm diagnosis that often involves excluding other potential causes. She also questioned Dr. Funes about his confidence that his analysis correctly identified patients only with HFpEF. Dr. Funes replied that the diagnostic codes his team used allowed for a clear distinction between patients identified with HFpEF and those with heart failure with reduced ejection fraction, but he also admitted that his study’s complete reliance on these codes introduced a limitation to the analysis.
 

Including patients with diastolic dysfunction as well as HFpEF

The study used data collected during 2010-2015 by the National Inpatient Sample, run by the U.S. Department of Health & Human Services in a case-control analysis that included 296,041 patients who had undergone some form of bariatric surgery and 2,004,804 people with no history of bariatric surgery selected as controls on the basis of their obesity.

The absolute numbers showed that, during the observation period, the incidence of acute HFpEF hospitalizations was 0.19% among those with prior bariatric surgery and 0.86% among those with no surgery, and the incidence of chronic heart failure hospitalizations was 0.01% among people with prior bariatric surgery and 0.05% among those without prior surgery. Dr. Funes said. He noted that, during the period studied patients, with HFpEF were usually identified as having diastolic heart failure, an older name for the same disease.

In multivariate analyses that adjusted for age, sex, race, hypertension, diabetes, smoking, and coronary artery disease, people without prior bariatric surgery and with hypertension had a 2.8-fold increased rate of acute hospitalizations for HFpEF, while those without hypertension or prior bariatric surgery had a 5.2-fold increased rate. In addition, control patients, regardless of hypertension status, had a 2.9-fold increased rate of hospitalizations for chronic HFpEF events. All these differences were statistically significant.

Dr. Funes also reported results from additional analyses that focused on a roughly 68,000-patient subgroup of those included in the study who had a history of coronary artery disease, including about 62,000 with no prior bariatric surgery and nearly 6,000 people with prior bariatric surgery. In a multivariate analysis of this subgroup, people without prior bariatric surgery had a 2.65-fold increased rate of hospitalization for a HFpEF event (either acute or chronic), compared with those who had undergone bariatric surgery.

Dr. Funes and associates and Dr. Kindel had no relevant disclosures.

mzoler@mdedge.com

Patients who underwent metabolic and bariatric surgery had fewer than half the number of hospitalizations for both acute and chronic episodes of heart failure with preserved ejection fraction (HFpEF) in a retrospective analysis of more than 2 million Americans collected in a national database.

In a multivariate analysis that adjusted for several variables patients without a history of bariatric surgery had three- to fivefold more hospitalizations for acute events involving HFpEF, and more than double the rate of hospitalizations for chronic HFpEF events, David R. Funes, MD, said at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

While this analysis has the limitations of being retrospective, observational, and entirely reliant on procedure codes to define medical histories and outcomes, it had the advantage of using a large database designed to represent the U.S. adult population, said Dr. Funes, a bariatric surgeon at the Cleveland Clinic in Weston, Fla.
 

HFpEF effects could ‘extend’ surgery’s use

The report “adds an important article to the literature where there is a true void in trying to discern the effect of bariatric surgery on HFpEF,” commented Tammy L. Kindel, MD, PhD, director of the bariatric surgery program at the Medical College of Wisconsin, Milwaukee, and designated discussant for the report. “Minimal studies [up to now] demonstrate that weight loss in any form can modify diastolic dysfunction in patients with HFpEF. Studies that investigate the impact of bariatric surgery on clinical outcomes in patients with HFpEF are probably the most important for extending use of metabolic surgery,” Dr. Kindel said.

She added that “one of the most difficult parts of studying HFpEF” is making a firm diagnosis that often involves excluding other potential causes. She also questioned Dr. Funes about his confidence that his analysis correctly identified patients only with HFpEF. Dr. Funes replied that the diagnostic codes his team used allowed for a clear distinction between patients identified with HFpEF and those with heart failure with reduced ejection fraction, but he also admitted that his study’s complete reliance on these codes introduced a limitation to the analysis.
 

Including patients with diastolic dysfunction as well as HFpEF

The study used data collected during 2010-2015 by the National Inpatient Sample, run by the U.S. Department of Health & Human Services in a case-control analysis that included 296,041 patients who had undergone some form of bariatric surgery and 2,004,804 people with no history of bariatric surgery selected as controls on the basis of their obesity.

The absolute numbers showed that, during the observation period, the incidence of acute HFpEF hospitalizations was 0.19% among those with prior bariatric surgery and 0.86% among those with no surgery, and the incidence of chronic heart failure hospitalizations was 0.01% among people with prior bariatric surgery and 0.05% among those without prior surgery. Dr. Funes said. He noted that, during the period studied patients, with HFpEF were usually identified as having diastolic heart failure, an older name for the same disease.

In multivariate analyses that adjusted for age, sex, race, hypertension, diabetes, smoking, and coronary artery disease, people without prior bariatric surgery and with hypertension had a 2.8-fold increased rate of acute hospitalizations for HFpEF, while those without hypertension or prior bariatric surgery had a 5.2-fold increased rate. In addition, control patients, regardless of hypertension status, had a 2.9-fold increased rate of hospitalizations for chronic HFpEF events. All these differences were statistically significant.

Dr. Funes also reported results from additional analyses that focused on a roughly 68,000-patient subgroup of those included in the study who had a history of coronary artery disease, including about 62,000 with no prior bariatric surgery and nearly 6,000 people with prior bariatric surgery. In a multivariate analysis of this subgroup, people without prior bariatric surgery had a 2.65-fold increased rate of hospitalization for a HFpEF event (either acute or chronic), compared with those who had undergone bariatric surgery.

Dr. Funes and associates and Dr. Kindel had no relevant disclosures.

mzoler@mdedge.com

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

A new clinical score has been developed, and externally validated, to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR).

“Despite the TAVR iterations, we recognize that bleeding remains a very important and perhaps also neglected issue. Indeed, no specifically developed standard algorithm existed before this to assess bleeding risk post-TAVR,” lead author Eliano Pio Navarese, MD, PhD, said in an interview.

Although bleeding rates can be as high as 9% at 30 days and between 3% and 11% in the first year, only a few studies have applied existing scores to TAVR patients, he noted.

The PREDICT-TAVR score includes six common variables and can be calculated by hand using a simple nomogram or a web-based calculator, with a dedicated website in the works, said Dr. Navarese, Nicolaus Copernicus University and SIRO MEDICINE Network, Bydgoszcz, Poland, and the University of Alberta, Edmonton.

A strength of the score is that machine-learning methods were used and the choice of variables optimized through recursive feature elimination and cross validation to remove the weakest variables, he said. Artificial intelligence, including use of random forest, naïve Bayes, and logistic regression classifiers, was also applied to the algorithms and the results cross-checked with standard multivariate analysis.

“It was a tremendous effort in terms of the analytics conducted,” Dr. Navarese said. “This is not a simple score but the integration of the most sophisticated machine learning methods and algorithms.”

Details are published in the June 14 issue of JACC: Cardiovascular Interventions.

The six variables used to calculate 30-day bleeding risk after TAVR and the points assigned to each are:

• blood hemoglobin (0-10 points)
• serum iron concentration (0-5 points)
• common femoral artery diameter (0-3 points)
•  (0-3 points)
• dual antiplatelet therapy (DAPT; 0-2 points)
• oral anticoagulation therapy (0-2 points)

The six items were selected among 104 baseline variables from 5,185 consecutive patients undergoing transfemoral TAVR in the prospective RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea) registry between March 2012 and December 2019, then validated in 5,043 patients in the prospective POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) between January 2013 and December 2019.

In the derivation cohort, 216 patients (4.2%) experienced bleeding events at 1 year, with 169 events (78%) occurring during the first 30 days.

PREDICT-TAVR exhibited high discriminatory power for bleeding events at 30 days, as reflected by an area under the curve (AUC) of 0.80 (95% confidence interval, 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was consistent at 0.79 (95% CI, 0.75-0.83).

PREDICT-TAVR also outperformed scores not developed for TAVR, such as the PARIS score for patients undergoing percutaneous coronary intervention (AUC, 0.69) and the well-validated HAS-BLED for patients receiving anticoagulation (AUC, 0.58; P < .001 for both).

In the validation cohort, the AUC for bleeding complications at 30 days was 0.78 (95% CI, 0.72-0.82) versus an AUC of 0.68 for PARIS and 0.66 for HAS-BLED.

A HAS-BLED score of 4 predicted a higher rate of severe bleeding and mortality in the year after transfemoral TAVR in the 2018 Japanese OCEAN-TAVI study.
 

Bleeding events by risk categories

Risk score quartiles identified as low risk were 8 points or less, as moderate risk were 8 to less than 10 points, as high risk were 10 to less than 12 points, and as very-high-risk score were above 12 points.

In the derivation cohort, 30-day bleeding events across quartiles were 0.8%, 1.1%, 2.5%, and 8.5%, respectively (overall P < .001).

Compared with the lowest quartile, bleeding risk was numerically higher for the second quartile (odds ratio, 1.75) and significantly higher in the third (OR, 2.0) and fourth (OR, 2.49) quartiles (P < .001 for both).

A landmark cumulative-event analysis showed a significantly greater risk of bleeding for the two highest quartiles up to 30 days; however, these differences were no longer significant from 30 days to 1 year, likely because of a limited number of events, the authors suggest. Similar results were seen in the validation cohort.

The number of patients in the high- and very-high-risk groups isn’t trivial, and bleeding rates reached as high as 12.6% in the highest quartile, Dr. Navarese observed. Guidelines recommend DAPT for 3 to 6 months after TAVR; however, emerging data, including a recent meta-analysis, suggest monotherapy may be a very good option.

“So, if you had a high bleeding risk and are considering postprocedural DAPT or anticoagulation, I would think twice rather than administering dual antiplatelet therapy or anticoagulation for a long time, or at least, I would consider the impact of this score on this choice,” he said.

Subgroup analyses showed AUCs ranging from 0.77 to 0.81 for subgroups such as age older than 80 years, diabetes, obesity, female sex, previous PCI, and New York Heart Association class III or IV.

Serum iron showed the highest AUC in the primary PREDICT-TAVR model; however, should iron levels be unavailable, a simplified score modeled without iron levels retained predictive power, yielding AUCs for 30-day bleeding of 0.78 in the derivation cohort and 0.75 in the validation cohort.

“PREDICT-TAVR score can impact clinical practice, not only selecting the optimal thrombotic regimen in certain high bleeding-risk populations but also to treat pre-TAVR anemia and iron deficiencies, which may affect outcomes,” Dr. Navarese said. “Of course, future prospective biological and clinical investigations are needed to elucidate the score and the role of the score’s treatable risk traits in reducing post-TAVR bleeding complications.”

Commenting for this news organization, Sunil Rao, MD, Duke University, Durham, N.C., said anemia is a covariant in many risk models for bleeding and vascular complications in PCI and acute coronary syndrome, but hemoglobin and iron levels are collinear.

“The problem I think is when you throw hemoglobin and iron in the same model, just by play of chance, one variable can knock out the other one,” he said. “So I don’t know necessarily if we need to start measuring iron on everyone. We certainly should be measuring hemoglobin, which I think most people will have, and if a patient has pre-existing anemia, that should be a red flag for us.”

Age and Society of Thoracic Surgeons (STS) risk score did not reach statistical significance in the model – likely reflecting the high-/extremely-high-risk patient population with an average STS score of 7.7 and average age of 82 years – but may become more important as TAVR is applied more widely, Dr. Rao and Zachary Wegermann, MD, Duke Clinical Research Institute, write in an accompanying editorial.

They also point out that the study was limited by a low rate of bleeding events, and, importantly, the score can’t distinguish between minor or major bleeding.

“It’s worth trying to repeat the analyses in lower-risk patients because we may find other covariates that are important,” Dr. Rao said in an interview. “The other thing we need to get to is probably being a little bit more sophisticated. The variables included in these models are the ones that are measured; they’re also the ones that are clinically apparent.”

“But there’s a whole area of genomic medicine, proteomic medicine, metabolomic medicine that, as it starts developing and becomes more and more sophisticated, my suspicion is that we’re going to get even more precise and accurate about patients’ risk, and it’s going to become more individualized, rather than just measuring variables like age and lab values,” he said.

In the meantime, having variables documented in the electronic health record, with hard stops deployed if variables aren’t measured, is “a step in the right direction,” he added.

Dr. Navarese has received research grants from Abbott, Amgen, and Medtronic and received lecture fees and honoraria from Amgen, AstraZeneca, Bayer, Pfizer, and Sanofi-Regeneron, outside the submitted work. Dr. Rao and Dr. Wegermann report no relevant financial disclosures.

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

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

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

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

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

Further evidence that powerful magnets in some Apple iPhones can interfere with cardiac implantable electronic devices (CIEDs) comes from a small study that also suggests some devices are more susceptible than others.

The iPhone 12 Pro Max with MagSafe technology interfered with CIEDs implanted in three consecutive patients presenting to an electrophysiology lab and in 8 of 11 implantable cardioverter defibrillators (ICDs) and pacemakers (72.7%) still in their original packaging.

The results, published in the Journal of the American Heart Association, are consistent with a widely publicized single-patient report this February and evidence of electromagnetic interference with fitness wristbands and e-cigarettes.

The MagSafe technology supports wireless charging and is optimized by a ring-shaped array of magnets. Although magnet mode activation has been shown to occur in CIEDs with exposure to a magnetic field as low as 10 gauss, the field strength of the iPhone 12 Pro Max can be greater than 50 G when in direct contact, the researchers determined.

“If this becomes a standard in a lot of the new smartphones or companies start to use stronger magnets ... then we will see more and more of these consumer electronic and device interactions,” senior author Michael Wu, MD, Brown University, Providence, R.I., told this news organization.

In a May advisory on these device interactions, the U.S. Food and Drug Administration also cautioned that the number of consumer electronics with strong magnets is expected to increase over time.

That trend appears to be already underway, with Forbes reporting in February that the MagSafe batteries will be “getting stronger” as part of upgrades to the iPhone 13 and Bloomberg reporting in advance of Apple’s annual developers conference this week that an upgraded version of MagSafe is in the works to support wireless charging for its iPad. MagSafe has not been used previously in iPads.

Although Apple has acknowledged that the iPhone 12 contains more magnets than previous iPhone models, it says “they’re not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” The company maintains a page that specifically warns about the potential for interactions and advises that consumers keep the iPhone and MagSafe accessories more than 15 cm (6 inches) away from medical devices.

Older-generation iPhones have not shown this risk, with only one case of interference reported with the iPhone 6 and an Apple Watch in 1,352 tests among 148 patients with CIEDs and leads from four different manufacturers.

In the present study, magnet reversion mode was triggered in all three patients when the iPhone 12 Pro Max was placed on the skin over the device.

The phone inhibited tachycardia therapies in Medtronic’s Amplia MRI Quad CRT-D and Abbott’s 1231-40 Fortify VR device.

The Boston Scientific V273 Intua CRT-P device, however, “appeared to be less susceptible, as we were only able to elicit transient temporary asynchronous pacing but no sustained response by the iPhone 12 Pro Max magnet,” Dr. Wu and colleagues note.

Among the 11 ex vivo CIEDs tested, placing the iPhone 12 Pro Max directly over the packaged device inhibited tachytherapies in Medtronic’s Visia AF MRI ICD and Abbott’s Fortify Assura DR ICD and Ellipse DR ICD.

The phone also led to asynchronous pacing in Medtronic’s Azure, Advisa MRI, and Adapta pacemakers and in Abbott’s Assurity MRI pacemaker.

Boston Scientific devices again “appeared to be less susceptible, as no clear magnet interference” was noted in the Dynagen ICD, Emblem MRI S-ICD, or Accolade MRI pacemaker, Dr. Wu reported. There was temporary asynchronous pacing but no sustained response in the company’s U125 Valitude pacemaker.

Using the Medtronic Visia AF MRI ICD, the researchers found that the iPhone 12 Pro Max was able to trigger magnet reversion mode at a distance up to 1.5 cm (0.6 inch) from the anterior aspect of the device ex vivo.

The difference in magnet response to the iPhone 12 Pro Max among the different devices is likely due to different hall-sensor magnet sensitivity, as all of the devices were susceptible to a standard donut magnet, Dr. Wu noted. Boston Scientific’s Accolade MRI pacemaker, for example, requires a magnet stronger than 70 G to activate magnet mode, according to the product manual.

“Even so, sometimes with our test, we were able to trigger a brief response,” he said. “The response isn’t as lasting as some of the other companies, but with the small sample size, I can only speculate and suggest that maybe it’s possible. But we always want a formal study through the company or other agencies to really pinpoint which company has more susceptible devices.”

As to whether manufacturers should build CIEDs less susceptible to today’s stronger magnets, Dr. Wu said it’s worth exploring, but there are pros and cons.

Although magnets in consumer devices have the potential to inhibit lifesaving therapies, a magnet is also very useful in certain medical settings, such as a quick way to ensure pacing without worrying about electrocautery noise during surgery or to deactivate a defibrillator if there’s noise resulting in inappropriate shocks.

“It would require an overhaul of a lot of the devices going forward, and I think that’s something that’s worth exploring, especially now that a lot of devices are using wireless communication, Bluetooth, and other communication technology,” he said.

Even though the study is small, Dr. Wu said, it does represent many of the available devices and has clinical implications, given that people often put their smartphones in a breast pocket.

“This report highlights the importance of public awareness regarding an interaction between CIEDs and a recently released smartphone model with magnetic charging capability,” Dr. Wu and colleagues conclude.

Apple was contacted for comment but had not responded at press time.

The authors reported no study funding or relevant conflicts of interests.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

Of patients with symptomatic, obstructive hypertrophic cardiomyopathy treated with the investigational oral agent mavacamten, more than twice as many, compared with placebo, had a very large improvement from baseline in their summary quality of life score after 30 weeks of treatment in a pivotal trial with 194 patients evaluable for this endpoint.

The trial’s health-related quality of life assessment, the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed an average improvement of more than 9 points, compared with placebo, in summary KCCQ scores among 98 mavacamten-treated patients, and a nearly 15-point improvement from baseline that represents a “moderate to large” improvement in overall health-related quality of life, John A. Spertus, MD, said at the annual scientific sessions of the American College of Cardiology.
 

Largest drug benefit ever seen in KCCQ

The 9-point average incremental improvement on mavacamten, a selective cardiac myosin inhibitor, compared with placebo-treated patients, is “the largest drug-mediated benefit we’ve ever observed on the KCCQ,” said Dr. Spertus, who spearheaded development of the KCCQ. Concurrently with his report the results also appeared online in the Lancet.

“Given the strength of the data, I’d reach for this drug early” to treat patients with obstructive hypertrophic cardiomyopathy (HCM), added Dr. Spertus, a professor and cardiovascular outcomes researcher at the University of Missouri–Kansas City and clinical director of outcomes research at Saint Luke’s Mid America Heart Institute, also in Kansas City.

No available treatment for obstructive HCM has had “as vigorous an assessment of impact on health status,” and the study that supplied the data he and his associates analyzed, EXPLORER-HCM, is “the largest trial ever done” in patients with HCM, he added.

Management guidelines for HCM released last year by the ACC and American Heart Association named beta-blockers “first-line” medical therapy for the disorder, with the calcium channel blockers verapamil or diltiazem named as “reasonable alternatives” to beta-blockers. However, these commonly used agents have “limited” evidence supporting health-status benefits in patients with HCM, Dr. Spertus and coauthors wrote in their report.
 

Longer follow-up needed

“This is an important study,” commented Matthew W. Martinez, MD, director of sports cardiology and a HCM specialist at Morristown (N.J.) Medical Center. But “given the longevity of HCM we need follow-up that goes beyond 30 weeks,” he said as designated discussant for the report.

EXPLORER-HCM randomized 251 patients with symptomatic obstructive HCM at 68 centers in 13 countries during 2018-2019. The 30-week trial’s primary outcome was a composite to assess clinical response, compared with baseline, that included a 1.5-mL/kg per min or greater increase in peak oxygen consumption (pVO₂) and at least one New York Heart Association (NYHA) functional class reduction; or a 3.0 mL/kg per min or greater improvement in pVO₂ and no worsening of NYHA class.

Patients averaged about 59 years of age, about 60% were men, and their pVO2 at entry averaged about 20 mL/kg per min. About 73% were in NYHA functional class II, with the remainder in functional class III. Patients received mavacamten as a once-daily oral dose that gradually up-titrated during the trial to reach targeted reductions in each patient’s plasma levels of the drug and in their left ventricular outflow tract gradient.

The results showed that, after 30 weeks on treatment, the primary endpoint was reached by 37% of 123 patients on mavacamten and by 17% of 128 patients on placebo, a significant difference in an intention-to-treat analysis. About 70% of patients completed their KCCQ after 30 weeks, which meant that fewer patients were in the quality of life analyses, according to the report that was published in The Lancet .

Based on these results the drug is now under consideration for approval by the Food and Drug Administration, with a decision expected by early 2022.
 

Benefit fades quickly when mavacamten stops

More detailed analysis of quality of life findings in the new report also showed that, while average KCCQ scores (both overall summary score and clinical summary score) steadily improved with mavacamten treatment, compared with control patients, through 18 weeks on treatment, the scores then roughly plateaued out to 30 weeks. This was followed by a sharp reversal back down to baseline levels and similar to control patients 8 weeks after stopping mavacamten, suggesting that the drug’s benefit quickly fades off treatment and hence must be taken chronically.

The responder analysis showed that 9% of patients on mavacamten had a worsening in their KCCQ overall summary scores by more than 5 points after 30 weeks, compared with 23% of the control patients. In contrast, a very large improvement in KCCQ score, defined as a rise of at least 20 points from baseline after 30 weeks, occurred in 36% of those who received mavacamten and in 15% of the controls. The between-group difference indicates a number needed to treat with mavacamten of roughly five to produce one additional patient with a very large improvement in KCCQ overall summary score, Dr. Spertus noted.

By design, all patients enrolled in EXPLORER-HCM had a left ventricular ejection fraction of at least 55%. During treatment, seven of the mavacamten-treated patients and two in the control arm had a transient decrease in their left ventricular ejection fraction to below 50%, although this later normalized in all affected patients. “An initial criticism” of the trial was that a significant percentage of mavacamten patients “developed left ventricular dysfunction” noted Dr. Martinez, but Dr. Spertus highlighted the poor apparent correlation between this phenomenon and quality of life self-assessment. Six of the seven patients on mavacamten who had a transient drop in their left ventricular ejection fraction had very large improvements in their KCCQ summary scores, Dr. Spertus reported.

Hypertrophic cardiomyopathy is a myocardial disorder characterized by primary left ventricular hypertrophy. Although a complex disease, HCM is broadly defined by pathologically enhanced cardiac actin-myosin interactions that result in hypercontractility, diastolic abnormalities, and dynamic left ventricular outflow tract obstruction. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin ATPase developed to target the underlying pathophysiology of HCM by reducing actin-myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.

EXPLORER-HCM was sponsored by MyoKardia, the company developing mavacamten and a subsidiary of Bristol-Myers Squibb. Dr. Spertus has been a consultant to MyoKardia, as well as to Abbott, Amgen, Bayer, Janssen, Merck, and Novartis. He has received research support from Abbott Vascular, and he holds the copyright for the KCCQ. Dr. Martinez has been a consultant to and received honoraria from Bristol-Myers Squibb.

mzoler@mdedge.com

Of patients with symptomatic, obstructive hypertrophic cardiomyopathy treated with the investigational oral agent mavacamten, more than twice as many, compared with placebo, had a very large improvement from baseline in their summary quality of life score after 30 weeks of treatment in a pivotal trial with 194 patients evaluable for this endpoint.

The trial’s health-related quality of life assessment, the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed an average improvement of more than 9 points, compared with placebo, in summary KCCQ scores among 98 mavacamten-treated patients, and a nearly 15-point improvement from baseline that represents a “moderate to large” improvement in overall health-related quality of life, John A. Spertus, MD, said at the annual scientific sessions of the American College of Cardiology.
 

Largest drug benefit ever seen in KCCQ

The 9-point average incremental improvement on mavacamten, a selective cardiac myosin inhibitor, compared with placebo-treated patients, is “the largest drug-mediated benefit we’ve ever observed on the KCCQ,” said Dr. Spertus, who spearheaded development of the KCCQ. Concurrently with his report the results also appeared online in the Lancet.

“Given the strength of the data, I’d reach for this drug early” to treat patients with obstructive hypertrophic cardiomyopathy (HCM), added Dr. Spertus, a professor and cardiovascular outcomes researcher at the University of Missouri–Kansas City and clinical director of outcomes research at Saint Luke’s Mid America Heart Institute, also in Kansas City.

No available treatment for obstructive HCM has had “as vigorous an assessment of impact on health status,” and the study that supplied the data he and his associates analyzed, EXPLORER-HCM, is “the largest trial ever done” in patients with HCM, he added.

Management guidelines for HCM released last year by the ACC and American Heart Association named beta-blockers “first-line” medical therapy for the disorder, with the calcium channel blockers verapamil or diltiazem named as “reasonable alternatives” to beta-blockers. However, these commonly used agents have “limited” evidence supporting health-status benefits in patients with HCM, Dr. Spertus and coauthors wrote in their report.
 

Longer follow-up needed

“This is an important study,” commented Matthew W. Martinez, MD, director of sports cardiology and a HCM specialist at Morristown (N.J.) Medical Center. But “given the longevity of HCM we need follow-up that goes beyond 30 weeks,” he said as designated discussant for the report.

EXPLORER-HCM randomized 251 patients with symptomatic obstructive HCM at 68 centers in 13 countries during 2018-2019. The 30-week trial’s primary outcome was a composite to assess clinical response, compared with baseline, that included a 1.5-mL/kg per min or greater increase in peak oxygen consumption (pVO₂) and at least one New York Heart Association (NYHA) functional class reduction; or a 3.0 mL/kg per min or greater improvement in pVO₂ and no worsening of NYHA class.

Patients averaged about 59 years of age, about 60% were men, and their pVO2 at entry averaged about 20 mL/kg per min. About 73% were in NYHA functional class II, with the remainder in functional class III. Patients received mavacamten as a once-daily oral dose that gradually up-titrated during the trial to reach targeted reductions in each patient’s plasma levels of the drug and in their left ventricular outflow tract gradient.

The results showed that, after 30 weeks on treatment, the primary endpoint was reached by 37% of 123 patients on mavacamten and by 17% of 128 patients on placebo, a significant difference in an intention-to-treat analysis. About 70% of patients completed their KCCQ after 30 weeks, which meant that fewer patients were in the quality of life analyses, according to the report that was published in The Lancet .

Based on these results the drug is now under consideration for approval by the Food and Drug Administration, with a decision expected by early 2022.
 

Benefit fades quickly when mavacamten stops

More detailed analysis of quality of life findings in the new report also showed that, while average KCCQ scores (both overall summary score and clinical summary score) steadily improved with mavacamten treatment, compared with control patients, through 18 weeks on treatment, the scores then roughly plateaued out to 30 weeks. This was followed by a sharp reversal back down to baseline levels and similar to control patients 8 weeks after stopping mavacamten, suggesting that the drug’s benefit quickly fades off treatment and hence must be taken chronically.

The responder analysis showed that 9% of patients on mavacamten had a worsening in their KCCQ overall summary scores by more than 5 points after 30 weeks, compared with 23% of the control patients. In contrast, a very large improvement in KCCQ score, defined as a rise of at least 20 points from baseline after 30 weeks, occurred in 36% of those who received mavacamten and in 15% of the controls. The between-group difference indicates a number needed to treat with mavacamten of roughly five to produce one additional patient with a very large improvement in KCCQ overall summary score, Dr. Spertus noted.

By design, all patients enrolled in EXPLORER-HCM had a left ventricular ejection fraction of at least 55%. During treatment, seven of the mavacamten-treated patients and two in the control arm had a transient decrease in their left ventricular ejection fraction to below 50%, although this later normalized in all affected patients. “An initial criticism” of the trial was that a significant percentage of mavacamten patients “developed left ventricular dysfunction” noted Dr. Martinez, but Dr. Spertus highlighted the poor apparent correlation between this phenomenon and quality of life self-assessment. Six of the seven patients on mavacamten who had a transient drop in their left ventricular ejection fraction had very large improvements in their KCCQ summary scores, Dr. Spertus reported.

Hypertrophic cardiomyopathy is a myocardial disorder characterized by primary left ventricular hypertrophy. Although a complex disease, HCM is broadly defined by pathologically enhanced cardiac actin-myosin interactions that result in hypercontractility, diastolic abnormalities, and dynamic left ventricular outflow tract obstruction. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin ATPase developed to target the underlying pathophysiology of HCM by reducing actin-myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.

EXPLORER-HCM was sponsored by MyoKardia, the company developing mavacamten and a subsidiary of Bristol-Myers Squibb. Dr. Spertus has been a consultant to MyoKardia, as well as to Abbott, Amgen, Bayer, Janssen, Merck, and Novartis. He has received research support from Abbott Vascular, and he holds the copyright for the KCCQ. Dr. Martinez has been a consultant to and received honoraria from Bristol-Myers Squibb.

mzoler@mdedge.com

Of patients with symptomatic, obstructive hypertrophic cardiomyopathy treated with the investigational oral agent mavacamten, more than twice as many, compared with placebo, had a very large improvement from baseline in their summary quality of life score after 30 weeks of treatment in a pivotal trial with 194 patients evaluable for this endpoint.

The trial’s health-related quality of life assessment, the Kansas City Cardiomyopathy Questionnaire (KCCQ), also showed an average improvement of more than 9 points, compared with placebo, in summary KCCQ scores among 98 mavacamten-treated patients, and a nearly 15-point improvement from baseline that represents a “moderate to large” improvement in overall health-related quality of life, John A. Spertus, MD, said at the annual scientific sessions of the American College of Cardiology.
 

Largest drug benefit ever seen in KCCQ

The 9-point average incremental improvement on mavacamten, a selective cardiac myosin inhibitor, compared with placebo-treated patients, is “the largest drug-mediated benefit we’ve ever observed on the KCCQ,” said Dr. Spertus, who spearheaded development of the KCCQ. Concurrently with his report the results also appeared online in the Lancet.

“Given the strength of the data, I’d reach for this drug early” to treat patients with obstructive hypertrophic cardiomyopathy (HCM), added Dr. Spertus, a professor and cardiovascular outcomes researcher at the University of Missouri–Kansas City and clinical director of outcomes research at Saint Luke’s Mid America Heart Institute, also in Kansas City.

No available treatment for obstructive HCM has had “as vigorous an assessment of impact on health status,” and the study that supplied the data he and his associates analyzed, EXPLORER-HCM, is “the largest trial ever done” in patients with HCM, he added.

Management guidelines for HCM released last year by the ACC and American Heart Association named beta-blockers “first-line” medical therapy for the disorder, with the calcium channel blockers verapamil or diltiazem named as “reasonable alternatives” to beta-blockers. However, these commonly used agents have “limited” evidence supporting health-status benefits in patients with HCM, Dr. Spertus and coauthors wrote in their report.
 

Longer follow-up needed

“This is an important study,” commented Matthew W. Martinez, MD, director of sports cardiology and a HCM specialist at Morristown (N.J.) Medical Center. But “given the longevity of HCM we need follow-up that goes beyond 30 weeks,” he said as designated discussant for the report.

EXPLORER-HCM randomized 251 patients with symptomatic obstructive HCM at 68 centers in 13 countries during 2018-2019. The 30-week trial’s primary outcome was a composite to assess clinical response, compared with baseline, that included a 1.5-mL/kg per min or greater increase in peak oxygen consumption (pVO₂) and at least one New York Heart Association (NYHA) functional class reduction; or a 3.0 mL/kg per min or greater improvement in pVO₂ and no worsening of NYHA class.

Patients averaged about 59 years of age, about 60% were men, and their pVO2 at entry averaged about 20 mL/kg per min. About 73% were in NYHA functional class II, with the remainder in functional class III. Patients received mavacamten as a once-daily oral dose that gradually up-titrated during the trial to reach targeted reductions in each patient’s plasma levels of the drug and in their left ventricular outflow tract gradient.

The results showed that, after 30 weeks on treatment, the primary endpoint was reached by 37% of 123 patients on mavacamten and by 17% of 128 patients on placebo, a significant difference in an intention-to-treat analysis. About 70% of patients completed their KCCQ after 30 weeks, which meant that fewer patients were in the quality of life analyses, according to the report that was published in The Lancet .

Based on these results the drug is now under consideration for approval by the Food and Drug Administration, with a decision expected by early 2022.
 

Benefit fades quickly when mavacamten stops

More detailed analysis of quality of life findings in the new report also showed that, while average KCCQ scores (both overall summary score and clinical summary score) steadily improved with mavacamten treatment, compared with control patients, through 18 weeks on treatment, the scores then roughly plateaued out to 30 weeks. This was followed by a sharp reversal back down to baseline levels and similar to control patients 8 weeks after stopping mavacamten, suggesting that the drug’s benefit quickly fades off treatment and hence must be taken chronically.

The responder analysis showed that 9% of patients on mavacamten had a worsening in their KCCQ overall summary scores by more than 5 points after 30 weeks, compared with 23% of the control patients. In contrast, a very large improvement in KCCQ score, defined as a rise of at least 20 points from baseline after 30 weeks, occurred in 36% of those who received mavacamten and in 15% of the controls. The between-group difference indicates a number needed to treat with mavacamten of roughly five to produce one additional patient with a very large improvement in KCCQ overall summary score, Dr. Spertus noted.

By design, all patients enrolled in EXPLORER-HCM had a left ventricular ejection fraction of at least 55%. During treatment, seven of the mavacamten-treated patients and two in the control arm had a transient decrease in their left ventricular ejection fraction to below 50%, although this later normalized in all affected patients. “An initial criticism” of the trial was that a significant percentage of mavacamten patients “developed left ventricular dysfunction” noted Dr. Martinez, but Dr. Spertus highlighted the poor apparent correlation between this phenomenon and quality of life self-assessment. Six of the seven patients on mavacamten who had a transient drop in their left ventricular ejection fraction had very large improvements in their KCCQ summary scores, Dr. Spertus reported.

Hypertrophic cardiomyopathy is a myocardial disorder characterized by primary left ventricular hypertrophy. Although a complex disease, HCM is broadly defined by pathologically enhanced cardiac actin-myosin interactions that result in hypercontractility, diastolic abnormalities, and dynamic left ventricular outflow tract obstruction. Mavacamten is a first-in-class, small-molecule, selective allosteric inhibitor of cardiac myosin ATPase developed to target the underlying pathophysiology of HCM by reducing actin-myosin cross-bridge formation, thereby reducing contractility and improving myocardial energetics.

EXPLORER-HCM was sponsored by MyoKardia, the company developing mavacamten and a subsidiary of Bristol-Myers Squibb. Dr. Spertus has been a consultant to MyoKardia, as well as to Abbott, Amgen, Bayer, Janssen, Merck, and Novartis. He has received research support from Abbott Vascular, and he holds the copyright for the KCCQ. Dr. Martinez has been a consultant to and received honoraria from Bristol-Myers Squibb.

mzoler@mdedge.com

Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.

“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.

There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.

Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.

Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.

“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”

Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.

The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.

In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).

“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”

For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”

Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: atrs.mcsmedicalaffairs@medtronic.com.

Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.

Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.

Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.

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

Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.

“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.

There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.

Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.

Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.

“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”

Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.

The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.

In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).

“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”

For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”

Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: atrs.mcsmedicalaffairs@medtronic.com.

Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.

Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.

Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.

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

Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.

“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.

There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.

Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.

Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.

“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”

Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.

The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.

In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).

“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”

For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”

Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: atrs.mcsmedicalaffairs@medtronic.com.

Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.

Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.

Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.

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

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

mzoler@mdedge.com

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

mzoler@mdedge.com

Although recent trial results have established the sodium glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin as a key new part of the recommended multidrug treatment regimen for patients with heart failure with reduced ejection fraction, the current U.S. cost for dapagliflozin means it has merely “intermediate” value when it comes to cost-effectiveness.

adventtr/iStock/Getty Images Plus

A typical regimen with dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) costs about $474/month or roughly $5,700/year based on Medicare pricing. After factoring in the incremental clinical benefits producing by dapagliflozin seen in the DAPA-HF pivotal trial that helped establish its role, this price produces a cost per quality-adjusted life-year (QALY) gain of about $84,000, which puts dapagliflozin squarely in the intermediate range for value set in 2014 by a task force of the American College of Cardiology and the American Heart Association.

This cost-effectiveness value depends largely on the proven efficacy of dapagliflozin (Farxiga) for decreasing the incidence of cardiovascular death among treated patients with HFrEF, and puts the drug’s value roughly on par with another agent recently approved to treat such patients, sacubitril/valsartan (Entresto), which carries a cost-effectiveness value of about $45,000/QALY.

The U.S. cost per QALY for dapagliflozin treatment of patients with HFrEF dwarfed the value numbers calculated for several other countries that were generally one-tenth this size. This disparity stemmed from both the relatively high price for dapagliflozin in the U.S. compared with other countries – nearly tenfold higher – and relatively higher costs for all types of U.S. medical care, Justin T. Parizo, MD, and coauthors said in a recent report. But the cost, and hence the cost per QALY, of dapagliflozin may soon drop because certain patents on the drug expired in October 2020, added Dr. Parizo, a cardiologist at Stanford (Calif.) University, and associates. Despite the expired patents, as of June 2021 no generic form of dapagliflozin appeared available for U.S. sale.
 

Medicare patients pay about $1,630/year out-of-pocket

“A key caveat” to this finding for dapagliflozin is that being cost-effective “is not by itself a mandate for routine clinical use,” Derek S. Chew, MD, and Daniel B. Mark, MD, said in an editorial that accompanied the report.

A major stumbling block for widespread U.S. prescribing of dapagliflozin to patients with HFrEF is its overall price tag for U.S. patients, estimated at $12 billion/year, as well as an out-of-pocket annual cost for individual Medicare patients of roughly $1,630/year. Adding this out-of-pocket cost to the copay for sacubitril/valsartan and two other much less expensive drug classes that together form the current mainstay, quadruple-drug regimen for HFrEF treatment means a potential annual cost paid by each Medicare patient of about $3,000, wrote Dr. Chew, a cardiologist, and Dr. Mark, a cardiologist and professor, both at Duke University, Durham, N.C.

They cited the precedent of the “unexpectedly slow” and “anemic” uptake of sacubitril/valsartan since its U.S. approval in 2015, a cost-effective agent with “comparable clinical effectiveness” to dapagliflozin. “Even with full inclusion [of sacubitril/valsartan] on formularies and elimination of preapproval requirements, use remains very low, and patient-borne out-of-pocket costs may be a key factor,” wrote Dr. Chew and Dr. Mark. They cited a results from a study that showed abandonment of new prescriptions at retail U.S. pharmacies spiked to a 60% rate when out-of-pocket cost exceeded $500.
 

More than what patients ‘can afford or are willing to spend’

The estimated $3,000-plus total out-of-pocket cost currently borne by some Medicare beneficiaries with HFrEF who have to shell out for both sacubitril/valsartan and dapagliflozin “appears to substantially exceed what many patients with heart failure can afford or are willing to spend,” wrote Dr. Chew and Dr. Mark.

Dr. Parizo and coauthors developed their cost-effectiveness model for dapagliflozin in treating HFrEF using primarily data collected in the DAPA-HF trial, which proved the efficacy of the drug for reducing cardiovascular deaths or acute heart failure events that led to hospitalization or intravenous outpatient treatment in more than 4,700 randomized patients with HFrEF. The trial enrolled roughly similar numbers of patients with or without type 2 diabetes.

The model showed an overall incremental cost-effectiveness ratio of $83,650/QALY, which was about the same regardless of whether patients also had type 2 diabetes. On a more granular level, the cost-effectiveness value estimate was $78,483/QALY in patients with mild health-status impairment due to their heart failure, and $97,608/QALY in patients with moderate impairment, a finding that underscores the importance of starting dapagliflozin treatment early in the course of HFrEF when disease effects are less severe. The analysis could not address value in patients with more advanced heart failure and in New York Heart Association functional class IV because fewer than 1% of patients in DAPA-HF were in this category.

Drug cost was a major determinant of cost-effectiveness. A 50% drop in cost from the Medicare benchmark of $473.64/month resulted in an incremental cost-effectiveness ratio of about $45,000/QALY (putting it into the high-value category based on the 2014 ACC/AHA formula), while a 50% rise in price yielded a value of nearly $123,000/QALY (still in the intermediate range, which spans from $50,000/QALY to $150,000/QALY). No other cost parameters had a meaningful effect on the cost-effectiveness calculation. The analyses also showed that using the basic cost assumptions, treatment with dapagliflozin needs to persist and remain effective for at least 44 months to produce a cost per QALY that’s less than $150,000. The authors stressed that their analysis considered heart failure effects and did not account for added benefit from treatment with dapagliflozin on preservation of renal function.

While it’s indisputable that treatment with dapagliflozin decreases health care costs by, for example, reducing hospitalizations for heart failure, each hospitalization costs just over $12,000, according to the assumptions made by Dr. Parizo and coauthors. But given dapagliflozin’s impact on this outcome, this cost saving translates into about $500/patient during 18 months on treatment (the median duration of treatment in DAPA-HF), which means the savings barely counterbalances the current cost of dapagliflozin treatment for 1 month, noted Dr. Chew and Dr. Mark.

The DAPA-HF trial was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Parizo had no disclosures and none of his coauthors had a relationship with AstraZeneca. Dr. Chew had no disclosures. Dr. Mark has received research grants from HeartFlow, Mayo Clinic, and Merck.

mzoler@mdedge.com