Cardiology News

The proportion of hypertensive patients with blood pressure control fell substantially in the United States during the COVID-19 pandemic, if the data from 24 health systems is representative of national trends.

GlobalStock/Getty Images

The decline in blood pressure control corresponded with – and might be explained by – a parallel decline in follow-up visits for uncontrolled hypertension from the same data source, according to Alanna M. Chamberlain, PhD, associate professor of epidemiology in the division of quantitative health sciences, Mayo Clinic, Rochester, Minn.

If the data are representative, a wave of cardiovascular (CV) events might be coming.

The study, called BP Track, collated electronic medical data on almost 1.8 million patients with hypertension from 2017 through 2020. Up until the end of 2019 and prior to the pandemic, slightly less than 60% of these patients had blood pressure control, defined as less than 140/90 mm Hg.

While the pre-COVID control rates were already “suboptimal,” a decline began almost immediately when the full force of the COVID-19 pandemic began in March of 2020, said Dr. Chamberlain in reporting the BP Track results at the American Heart Association scientific sessions.

When graphed from the start of the pandemic until the end of 2020, the proportion under control fell 7.2% to a level just above 50%. For the more rigorous target of less than 130/80 mm Hg, the proportion fell 4.6% over the same period of time, leaving only about 25% at that level of control.

Repeat visits for BP control rebounded

The proportion of patients with a repeat office visit within 4 weeks of a diagnosis of uncontrolled hypertension fell even more steeply, reaching a nadir at about the middle of 2020, but it was followed by a partial recovery. The rate was 5% lower by the end of 2020, relative to the prepandemic rate (31.7% vs. 36.7%), but that was 5% higher than the nadir.

A similar phenomenon was observed with several other metrics. For example, there was a steep, immediate fall correlating with the onset of the pandemic in the proportion of patients who achieved at least a 10–mm Hg reduction or a BP under 140/90 mm Hg when treated for hypertension. Again, the nadir in this proportion was reached in about mid-2020 followed by a partial recovery. By the end of 2020, 5.9% fewer patients were achieving 10–mm Hg or better improvement in BP control when treated relative to the prepandemic level (23.8% vs. 29.7%), but this level was almost 10% higher than the nadir.

Data based on electronic medical records

The nearly 1.8 million patient records evaluated in the BP Track study were drawn from the 24 centers participating in the PCORnet Blood Pressure Control Laboratory Surveillance System. Nationally distributed, 18 of the 24 systems were academically affiliated.

When stratified by race, the proportion of Asians meeting the definition of BP control prior to the pandemic was about 5% higher than the overall average, and the proportion in Blacks was more than 5% lower. Whites had rates of blood pressure control very near the average. The relative declines in BP and the proportion of patients with uncontrolled blood pressure who had a repeat visit within 4 weeks during the pandemic were generally parallel across racial groups.

The implications of these data and the role of the COVID-19 pandemic on blood pressure control are “concerning,” according to Adam Bress, PharmD, department of population health sciences, University of Utah, Salt Lake City.

Citing a study published in 2020 that suggested blood pressure control rates in the United States were already declining before the COVID-19 pandemic, he said the COVID-19 epidemic appears to be exacerbating an existing problem. He expressed particular concern for populations who already have low rates of control, such as African Americans.

“The impact of COVID-19 is likely to be disproportionately greater for underserved and minoritized patients,” said Dr. Bress, who was the lead author of a recent article on this specific topic.

The implication of BP Track is that a wave of cardiovascular events will be coming if the data are nationally representative.

“A recent meta-analysis shows that each 5–mm Hg reduction in blood pressure is associated with age-related reductions in CV events,” Dr. Bress said. For those 55 years of age or older, he said the risk reduction is about 10%. Given that the inverse is almost certainly true, he expects diminishing blood pressure control, whether COVID-19-related or not, to translate into increased CV events.

However, there is no guarantee that the BP Track data are representative of the U.S. population, cautioned Eugene Yang, MD, professor in the division of cardiology, University of Washington, Seattle. Even though a large group of patients was included, they were largely drawn from academic centers.

Nevertheless, Dr. Yang, who chairs the Hypertension Working Group of the American College of Cardiology’s Prevention of Cardiovascular Disease Council, acknowledged that the implications are “scary.”

If the data are representative, “this type of reduction in blood pressure control would be expected to have a significant impact on morbidity and mortality, but we also have to think of all the variables that were not tracked and might add to risk,” he said. He named such risk factors as weight gain, diminished exercise, and increased alcohol consumption, which have been cited by others as being exacerbated by the pandemic.

If these lead to more cardiovascular events on a population basis, the timing of these events would be expected to be age dependent.

“If you look at the patients included in this study, about 50% were 65 years of age or older. In a population like this you would expect to see an increase in events sooner rather than later,” said Dr. Wang.

In other words, if the trial is representative, a wave of cardiovascular events might be seen in the most vulnerable patients “within the next few years,” Dr. Yang speculated.

Dr. Chamberlain reports a research grant from EpidStrategies. Dr. Bress and Dr. Yang report no potential financial conflicts of interest.

The proportion of hypertensive patients with blood pressure control fell substantially in the United States during the COVID-19 pandemic, if the data from 24 health systems is representative of national trends.

GlobalStock/Getty Images

The decline in blood pressure control corresponded with – and might be explained by – a parallel decline in follow-up visits for uncontrolled hypertension from the same data source, according to Alanna M. Chamberlain, PhD, associate professor of epidemiology in the division of quantitative health sciences, Mayo Clinic, Rochester, Minn.

If the data are representative, a wave of cardiovascular (CV) events might be coming.

The study, called BP Track, collated electronic medical data on almost 1.8 million patients with hypertension from 2017 through 2020. Up until the end of 2019 and prior to the pandemic, slightly less than 60% of these patients had blood pressure control, defined as less than 140/90 mm Hg.

While the pre-COVID control rates were already “suboptimal,” a decline began almost immediately when the full force of the COVID-19 pandemic began in March of 2020, said Dr. Chamberlain in reporting the BP Track results at the American Heart Association scientific sessions.

When graphed from the start of the pandemic until the end of 2020, the proportion under control fell 7.2% to a level just above 50%. For the more rigorous target of less than 130/80 mm Hg, the proportion fell 4.6% over the same period of time, leaving only about 25% at that level of control.

Repeat visits for BP control rebounded

The proportion of patients with a repeat office visit within 4 weeks of a diagnosis of uncontrolled hypertension fell even more steeply, reaching a nadir at about the middle of 2020, but it was followed by a partial recovery. The rate was 5% lower by the end of 2020, relative to the prepandemic rate (31.7% vs. 36.7%), but that was 5% higher than the nadir.

A similar phenomenon was observed with several other metrics. For example, there was a steep, immediate fall correlating with the onset of the pandemic in the proportion of patients who achieved at least a 10–mm Hg reduction or a BP under 140/90 mm Hg when treated for hypertension. Again, the nadir in this proportion was reached in about mid-2020 followed by a partial recovery. By the end of 2020, 5.9% fewer patients were achieving 10–mm Hg or better improvement in BP control when treated relative to the prepandemic level (23.8% vs. 29.7%), but this level was almost 10% higher than the nadir.

Data based on electronic medical records

The nearly 1.8 million patient records evaluated in the BP Track study were drawn from the 24 centers participating in the PCORnet Blood Pressure Control Laboratory Surveillance System. Nationally distributed, 18 of the 24 systems were academically affiliated.

When stratified by race, the proportion of Asians meeting the definition of BP control prior to the pandemic was about 5% higher than the overall average, and the proportion in Blacks was more than 5% lower. Whites had rates of blood pressure control very near the average. The relative declines in BP and the proportion of patients with uncontrolled blood pressure who had a repeat visit within 4 weeks during the pandemic were generally parallel across racial groups.

The implications of these data and the role of the COVID-19 pandemic on blood pressure control are “concerning,” according to Adam Bress, PharmD, department of population health sciences, University of Utah, Salt Lake City.

Citing a study published in 2020 that suggested blood pressure control rates in the United States were already declining before the COVID-19 pandemic, he said the COVID-19 epidemic appears to be exacerbating an existing problem. He expressed particular concern for populations who already have low rates of control, such as African Americans.

“The impact of COVID-19 is likely to be disproportionately greater for underserved and minoritized patients,” said Dr. Bress, who was the lead author of a recent article on this specific topic.

The implication of BP Track is that a wave of cardiovascular events will be coming if the data are nationally representative.

“A recent meta-analysis shows that each 5–mm Hg reduction in blood pressure is associated with age-related reductions in CV events,” Dr. Bress said. For those 55 years of age or older, he said the risk reduction is about 10%. Given that the inverse is almost certainly true, he expects diminishing blood pressure control, whether COVID-19-related or not, to translate into increased CV events.

However, there is no guarantee that the BP Track data are representative of the U.S. population, cautioned Eugene Yang, MD, professor in the division of cardiology, University of Washington, Seattle. Even though a large group of patients was included, they were largely drawn from academic centers.

Nevertheless, Dr. Yang, who chairs the Hypertension Working Group of the American College of Cardiology’s Prevention of Cardiovascular Disease Council, acknowledged that the implications are “scary.”

If the data are representative, “this type of reduction in blood pressure control would be expected to have a significant impact on morbidity and mortality, but we also have to think of all the variables that were not tracked and might add to risk,” he said. He named such risk factors as weight gain, diminished exercise, and increased alcohol consumption, which have been cited by others as being exacerbated by the pandemic.

If these lead to more cardiovascular events on a population basis, the timing of these events would be expected to be age dependent.

“If you look at the patients included in this study, about 50% were 65 years of age or older. In a population like this you would expect to see an increase in events sooner rather than later,” said Dr. Wang.

In other words, if the trial is representative, a wave of cardiovascular events might be seen in the most vulnerable patients “within the next few years,” Dr. Yang speculated.

Dr. Chamberlain reports a research grant from EpidStrategies. Dr. Bress and Dr. Yang report no potential financial conflicts of interest.

The proportion of hypertensive patients with blood pressure control fell substantially in the United States during the COVID-19 pandemic, if the data from 24 health systems is representative of national trends.

GlobalStock/Getty Images

The decline in blood pressure control corresponded with – and might be explained by – a parallel decline in follow-up visits for uncontrolled hypertension from the same data source, according to Alanna M. Chamberlain, PhD, associate professor of epidemiology in the division of quantitative health sciences, Mayo Clinic, Rochester, Minn.

If the data are representative, a wave of cardiovascular (CV) events might be coming.

The study, called BP Track, collated electronic medical data on almost 1.8 million patients with hypertension from 2017 through 2020. Up until the end of 2019 and prior to the pandemic, slightly less than 60% of these patients had blood pressure control, defined as less than 140/90 mm Hg.

While the pre-COVID control rates were already “suboptimal,” a decline began almost immediately when the full force of the COVID-19 pandemic began in March of 2020, said Dr. Chamberlain in reporting the BP Track results at the American Heart Association scientific sessions.

When graphed from the start of the pandemic until the end of 2020, the proportion under control fell 7.2% to a level just above 50%. For the more rigorous target of less than 130/80 mm Hg, the proportion fell 4.6% over the same period of time, leaving only about 25% at that level of control.

Repeat visits for BP control rebounded

The proportion of patients with a repeat office visit within 4 weeks of a diagnosis of uncontrolled hypertension fell even more steeply, reaching a nadir at about the middle of 2020, but it was followed by a partial recovery. The rate was 5% lower by the end of 2020, relative to the prepandemic rate (31.7% vs. 36.7%), but that was 5% higher than the nadir.

A similar phenomenon was observed with several other metrics. For example, there was a steep, immediate fall correlating with the onset of the pandemic in the proportion of patients who achieved at least a 10–mm Hg reduction or a BP under 140/90 mm Hg when treated for hypertension. Again, the nadir in this proportion was reached in about mid-2020 followed by a partial recovery. By the end of 2020, 5.9% fewer patients were achieving 10–mm Hg or better improvement in BP control when treated relative to the prepandemic level (23.8% vs. 29.7%), but this level was almost 10% higher than the nadir.

Data based on electronic medical records

The nearly 1.8 million patient records evaluated in the BP Track study were drawn from the 24 centers participating in the PCORnet Blood Pressure Control Laboratory Surveillance System. Nationally distributed, 18 of the 24 systems were academically affiliated.

When stratified by race, the proportion of Asians meeting the definition of BP control prior to the pandemic was about 5% higher than the overall average, and the proportion in Blacks was more than 5% lower. Whites had rates of blood pressure control very near the average. The relative declines in BP and the proportion of patients with uncontrolled blood pressure who had a repeat visit within 4 weeks during the pandemic were generally parallel across racial groups.

The implications of these data and the role of the COVID-19 pandemic on blood pressure control are “concerning,” according to Adam Bress, PharmD, department of population health sciences, University of Utah, Salt Lake City.

Citing a study published in 2020 that suggested blood pressure control rates in the United States were already declining before the COVID-19 pandemic, he said the COVID-19 epidemic appears to be exacerbating an existing problem. He expressed particular concern for populations who already have low rates of control, such as African Americans.

“The impact of COVID-19 is likely to be disproportionately greater for underserved and minoritized patients,” said Dr. Bress, who was the lead author of a recent article on this specific topic.

The implication of BP Track is that a wave of cardiovascular events will be coming if the data are nationally representative.

“A recent meta-analysis shows that each 5–mm Hg reduction in blood pressure is associated with age-related reductions in CV events,” Dr. Bress said. For those 55 years of age or older, he said the risk reduction is about 10%. Given that the inverse is almost certainly true, he expects diminishing blood pressure control, whether COVID-19-related or not, to translate into increased CV events.

However, there is no guarantee that the BP Track data are representative of the U.S. population, cautioned Eugene Yang, MD, professor in the division of cardiology, University of Washington, Seattle. Even though a large group of patients was included, they were largely drawn from academic centers.

Nevertheless, Dr. Yang, who chairs the Hypertension Working Group of the American College of Cardiology’s Prevention of Cardiovascular Disease Council, acknowledged that the implications are “scary.”

If the data are representative, “this type of reduction in blood pressure control would be expected to have a significant impact on morbidity and mortality, but we also have to think of all the variables that were not tracked and might add to risk,” he said. He named such risk factors as weight gain, diminished exercise, and increased alcohol consumption, which have been cited by others as being exacerbated by the pandemic.

If these lead to more cardiovascular events on a population basis, the timing of these events would be expected to be age dependent.

“If you look at the patients included in this study, about 50% were 65 years of age or older. In a population like this you would expect to see an increase in events sooner rather than later,” said Dr. Wang.

In other words, if the trial is representative, a wave of cardiovascular events might be seen in the most vulnerable patients “within the next few years,” Dr. Yang speculated.

Dr. Chamberlain reports a research grant from EpidStrategies. Dr. Bress and Dr. Yang report no potential financial conflicts of interest.

Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.

Of the trial’s 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared with standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2-3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.

The findings “advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status,” Marko Banovic, MD, PhD, said during his presentation at the American Heart Association scientific sessions.

Dr. Banovic, from the University of Belgrade Medical School in Serbia, is coprincipal investigator on the trial, called AVATAR (Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study’s publication in Circulation, timed to coincide with his AHA presentation.

“The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities,” Dr. Banovic told this news organization.

European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden (the Netherlands) University Medical Center, an invited discussant for the AVATAR presentation.

AVATAR does suggest that “early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment,” she said. “But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed.”

The trial has strengths, compared with the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Dr. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic – stress testing wasn›t routinely performed.

In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Dr. Banovic noted. As he and his colleagues write, the trial expands on RECOVERY “by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function.”

A role for TAVR?

Guidelines in general “can be very conservative and lag behind evidence a bit,” Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minn., who is not associated with AVATAR, said in an interview.

“I think when we see patients clinically, we can advise them that if they don’t have symptoms and they do have severe aortic stenosis,” she said, “they’re likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes.”

The results of AVATAR, in which valve replacement consisted only of SAVR, “probably could be extrapolated” to transcatheter aortic valve replacement (TAVR), Dr. Pellikka observed. “Certainly, TAVR is the procedure that patients come asking for. It’s attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial.”

In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Dr. Banovic said in an interview. Importantly, the trial’s patients were at low surgical risk and free of major chronic diseases or other important health concerns.

“Frailty and older age are known risk factors for suboptimal recovery” after SAVR, Dr. Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be “more suitable for TAVR than SAVR, based on the TAVR-vs.-SAVR results in symptomatic AS patients,” he said.

“One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications,” but that would require more supporting evidence, Dr. Banovic said.

Confirmed asymptomatic

AVATAR, conducted at nine centers in seven countries in the European Union, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.

The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort’s average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.

The 78 patients in the early-surgery group “were expected” to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only one periprocedural death, for an operative mortality of 1.4%.

The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.

The rate of the primary endpoint – death from any cause, acute myocardial infarction, stroke, or unplanned HF hospitalization – was 16.6% in the early-surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio by intention-to-treat analysis was 0.46 (95% confidence interval, 0.23-0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19-0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.

If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. “Echocardiography would be the screening test for aortic stenosis, but it’s fairly expensive and therefore has never been advocated as a test to screen everyone,” Dr. Pellikka observed.

“But things are changing,” given innovations such as point-of-care ultrasonography and machine learning, she noted. “Artificial intelligence is progressing in its application to echocardiography, and it’s conceivable that in the future, there might be some abbreviated or screening type of test. But I don’t think we’re quite there yet.”

Dr. Banovic had no conflicts; disclosures for the other authors are in the report. Dr. Delgado disclosed speaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Dr. Pellikka disclosed receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.

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

Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.

Of the trial’s 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared with standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2-3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.

The findings “advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status,” Marko Banovic, MD, PhD, said during his presentation at the American Heart Association scientific sessions.

Dr. Banovic, from the University of Belgrade Medical School in Serbia, is coprincipal investigator on the trial, called AVATAR (Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study’s publication in Circulation, timed to coincide with his AHA presentation.

“The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities,” Dr. Banovic told this news organization.

European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden (the Netherlands) University Medical Center, an invited discussant for the AVATAR presentation.

AVATAR does suggest that “early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment,” she said. “But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed.”

The trial has strengths, compared with the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Dr. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic – stress testing wasn›t routinely performed.

In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Dr. Banovic noted. As he and his colleagues write, the trial expands on RECOVERY “by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function.”

A role for TAVR?

Guidelines in general “can be very conservative and lag behind evidence a bit,” Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minn., who is not associated with AVATAR, said in an interview.

“I think when we see patients clinically, we can advise them that if they don’t have symptoms and they do have severe aortic stenosis,” she said, “they’re likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes.”

The results of AVATAR, in which valve replacement consisted only of SAVR, “probably could be extrapolated” to transcatheter aortic valve replacement (TAVR), Dr. Pellikka observed. “Certainly, TAVR is the procedure that patients come asking for. It’s attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial.”

In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Dr. Banovic said in an interview. Importantly, the trial’s patients were at low surgical risk and free of major chronic diseases or other important health concerns.

“Frailty and older age are known risk factors for suboptimal recovery” after SAVR, Dr. Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be “more suitable for TAVR than SAVR, based on the TAVR-vs.-SAVR results in symptomatic AS patients,” he said.

“One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications,” but that would require more supporting evidence, Dr. Banovic said.

Confirmed asymptomatic

AVATAR, conducted at nine centers in seven countries in the European Union, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.

The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort’s average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.

The 78 patients in the early-surgery group “were expected” to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only one periprocedural death, for an operative mortality of 1.4%.

The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.

The rate of the primary endpoint – death from any cause, acute myocardial infarction, stroke, or unplanned HF hospitalization – was 16.6% in the early-surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio by intention-to-treat analysis was 0.46 (95% confidence interval, 0.23-0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19-0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.

If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. “Echocardiography would be the screening test for aortic stenosis, but it’s fairly expensive and therefore has never been advocated as a test to screen everyone,” Dr. Pellikka observed.

“But things are changing,” given innovations such as point-of-care ultrasonography and machine learning, she noted. “Artificial intelligence is progressing in its application to echocardiography, and it’s conceivable that in the future, there might be some abbreviated or screening type of test. But I don’t think we’re quite there yet.”

Dr. Banovic had no conflicts; disclosures for the other authors are in the report. Dr. Delgado disclosed speaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Dr. Pellikka disclosed receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.

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

Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.

Of the trial’s 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared with standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2-3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.

The findings “advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status,” Marko Banovic, MD, PhD, said during his presentation at the American Heart Association scientific sessions.

Dr. Banovic, from the University of Belgrade Medical School in Serbia, is coprincipal investigator on the trial, called AVATAR (Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study’s publication in Circulation, timed to coincide with his AHA presentation.

“The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities,” Dr. Banovic told this news organization.

European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden (the Netherlands) University Medical Center, an invited discussant for the AVATAR presentation.

AVATAR does suggest that “early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment,” she said. “But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed.”

The trial has strengths, compared with the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Dr. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic – stress testing wasn›t routinely performed.

In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Dr. Banovic noted. As he and his colleagues write, the trial expands on RECOVERY “by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function.”

A role for TAVR?

Guidelines in general “can be very conservative and lag behind evidence a bit,” Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minn., who is not associated with AVATAR, said in an interview.

“I think when we see patients clinically, we can advise them that if they don’t have symptoms and they do have severe aortic stenosis,” she said, “they’re likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes.”

The results of AVATAR, in which valve replacement consisted only of SAVR, “probably could be extrapolated” to transcatheter aortic valve replacement (TAVR), Dr. Pellikka observed. “Certainly, TAVR is the procedure that patients come asking for. It’s attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial.”

In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Dr. Banovic said in an interview. Importantly, the trial’s patients were at low surgical risk and free of major chronic diseases or other important health concerns.

“Frailty and older age are known risk factors for suboptimal recovery” after SAVR, Dr. Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be “more suitable for TAVR than SAVR, based on the TAVR-vs.-SAVR results in symptomatic AS patients,” he said.

“One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications,” but that would require more supporting evidence, Dr. Banovic said.

Confirmed asymptomatic

AVATAR, conducted at nine centers in seven countries in the European Union, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.

The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort’s average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.

The 78 patients in the early-surgery group “were expected” to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only one periprocedural death, for an operative mortality of 1.4%.

The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.

The rate of the primary endpoint – death from any cause, acute myocardial infarction, stroke, or unplanned HF hospitalization – was 16.6% in the early-surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio by intention-to-treat analysis was 0.46 (95% confidence interval, 0.23-0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19-0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.

If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. “Echocardiography would be the screening test for aortic stenosis, but it’s fairly expensive and therefore has never been advocated as a test to screen everyone,” Dr. Pellikka observed.

“But things are changing,” given innovations such as point-of-care ultrasonography and machine learning, she noted. “Artificial intelligence is progressing in its application to echocardiography, and it’s conceivable that in the future, there might be some abbreviated or screening type of test. But I don’t think we’re quite there yet.”

Dr. Banovic had no conflicts; disclosures for the other authors are in the report. Dr. Delgado disclosed speaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Dr. Pellikka disclosed receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.

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

Patients with acute coronary syndromes who have been taking the antiplatelet medication, ticagrelor, and who need coronary artery bypass surgery (CABG) may be able to safely have the procedure earlier than typically recommended, a new randomized trial suggests.

The RAPID CABG trial found that early surgery 2-3 days after ticagrelor cessation was noninferior in incurring severe or massive perioperative bleeding, compared with waiting 5-7 days. There was also no significant difference in TIMI CABG or Bleeding Academic Research Consortium (BARC) type 4 or 5 bleeding.

Patients in the delayed group had a numerically higher number of ischemic events requiring earlier surgery and had a longer hospital stay.

The study was presented at the American Heart Association scientific sessions.

“RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” said lead investigator Derek So, MD.

Dr. So, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa, explained that ticagrelor is a first-line antiplatelet agent for patients with acute coronary syndromes (ACS), but around 10% of patients presenting with ACS require CABG surgery.

A major concern among patients requiring bypass surgery is perioperative bleeding, and it has been shown that patients undergoing urgent bypass within 24 hours of the last dose of ticagrelor have increased mortality. Accordingly, guidelines suggest a waiting period for patients not requiring urgent bypass surgery, Dr. So noted.

Current North American guidelines suggest a waiting period of at least 5 days after stopping ticagrelor before bypass surgery. In contrast, the updated European and Japanese guidelines suggest a waiting period of 3 days.

Dr. So noted that all of the guidelines are based on cohort studies and pharmacodynamic studies, with no randomized evidence. Pharmacodynamic studies have shown that at 48 hours after the last dose of ticagrelor, the level of platelet inhibition drops to the same levels seen with long-term treatment with clopidogrel, a weaker antiplatelet drug, and after 120 hours (5 days) the effect has completely worn off.

Dr. So concluded that these new results from the RAPID CABG trial “may influence future iterations of North American guidelines with reduced waiting prior to bypass surgery” for patients receiving ticagrelor, and “they could also strengthen the level of evidence in European and Asian guidelines.”

Designated discussant of the RAPID CABG trial, Roxana Mehran, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, said this was a “very important study,” being the only randomized trial to look at this issue to date.

Dr. Mehran noted that the results showed a similar number of major life-threatening bleeding events in the early and delayed groups and met the noninferiority endpoint, but she pointed out that the trial had a small sample size and a small number of events. “Therefore, larger trials are needed to verify these important and encouraging results.”

However, she concluded that these results should be considered in decisions about the timing of bypass surgery in patients receiving ticagrelor. “I will be changing my practice and sending patients earlier based on this data,” she said.

 RAPID CABG

RAPID CABG was a physician-initiated multicenter randomized study evaluating the safety of early surgery at 2-3 days after ticagrelor cessation, compared with a delay of 5-7 days among patients presenting with ACS who required nonemergency CABG surgery.

The study enrolled 143 patients with ACS who were receiving ticagrelor and needed CABG surgery. Patients with stenting for culprit lesions, those requiring urgent surgery (less than 24 hours after presentation), and those requiring valve surgery were excluded.   

Three patients declined surgery, and several others underwent surgery outside the assigned time window, so the results were based on the per protocol analysis of patients who actually had CABG in the assigned time window: 65 patients in the early CABG group and 58 in the delayed group.

The mean time from last ticagrelor dose to surgery was 3 days in the early group and 6 days in the delayed group.

Platelet reactivity on the VerifyNow test showed more residual antiplatelet activity in the early group, with P2Y12 reaction unit (PRU) levels of 200 (vs. 251 in the delayed group). This test measures the extent of platelet aggregation in the presence of P2Y12-inhibitor drugs, with lower PRU levels showing stronger antiplatelet effects.

The primary outcome of the study was severe or massive bleeding by Universal Definition of Perioperative Bleeding (UDPB) class 3 or 4. This is defined as a blood transfusions of more than 5 units of red blood cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000 mL in the first 12 hours, and reoperation for bleeding.

Results showed that 4.6% of the early-surgery group had a primary outcome bleeding event, compared with 5.2% of the delayed surgery group, meeting the criteria for noninferiority (P = .0253 for noninferiority).

Individual components of the primary endpoint showed three class 3 (severe) bleeding events in both groups and no class 4 (massive) bleeding events in either group.  

In terms of other bleeding outcomes, TIMI CABG bleeding occurred in two patients (3.1%) in the early-surgery group vs. no patients in the delayed group; BARC 4 bleeding occurred in two patients (3.1%) in the early group versus none in the delayed group, and there were no BARC 5 bleeding events in either group.

In the intention-to-treat analysis, ischemic events before surgery occurred in six patients (8.7%) in the delayed group (one myocardial infarction, four cases of recurrent ischemia, and one ventricular tachycardia) versus none in the early group.

Cumulative 6-month ischemic events occurred in nine patients (13.0%) in the delayed group vs. four patients (5.6%) in the early group, the difference being driven by nonfatal MI and recurrent ischemia.  

There were no cardiovascular deaths in either group and one all-cause death in both groups.

Patients undergoing early surgery also had a shorter hospitalization, with a median length of stay of 9 days versus 12 days in the delayed group.

Larger trial needed

Commenting on the RAPID CABG study at an AHA press conference, Joanna Chikwe, MD, chair of the cardiac surgery department at Cedars-Sinai Medical Center, Los Angeles, said the results were in line with her practice.

“These results confirm what I already think is safe,” she said. “I’m comfortable going within 48 hours. But we individualize our approach, so it was helpful that the study investigators included platelet reactivity data. The interesting thing for me in this study was the number of adverse events in patients who waited longer.” 

Dr. Chikwe said her top-line message was that “Surgery looked incredibly safe; there was amazingly low mortality. And if a patient has an indication for surgery, waiting does not serve you well.”

However, she also cautioned that the trial was somewhat underpowered, with a small number of events that drove the primary outcome, leading to some uncertainty on the results.

“The RAPID trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Dr. Chikwe noted.  

She added that clinical trials in cardiac surgery are driven by inherent challenges. “Cardiac surgery is not very common, and it is hard to recruit patients into these trials, so you are generally tied to a small number of patients, and you therefore have to be extremely thoughtful about the study design. It is almost a given that you will need to use surrogate endpoints, and the choice of the surrogate endpoint can determine which way the trial goes.”

The RAPID CABG study was funded by the Canadian Institutes of Health Research. Dr. So reports research support, consultancy, or speaker’s fees from AggreDyne, Roche Diagnostics, Fujimori Kogyo, and AstraZeneca Canada. Dr. Mehran reports that her institution has received significant trial funding from AstraZeneca (the manufacturer of ticagrelor).  

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

Patients with acute coronary syndromes who have been taking the antiplatelet medication, ticagrelor, and who need coronary artery bypass surgery (CABG) may be able to safely have the procedure earlier than typically recommended, a new randomized trial suggests.

The RAPID CABG trial found that early surgery 2-3 days after ticagrelor cessation was noninferior in incurring severe or massive perioperative bleeding, compared with waiting 5-7 days. There was also no significant difference in TIMI CABG or Bleeding Academic Research Consortium (BARC) type 4 or 5 bleeding.

Patients in the delayed group had a numerically higher number of ischemic events requiring earlier surgery and had a longer hospital stay.

The study was presented at the American Heart Association scientific sessions.

“RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” said lead investigator Derek So, MD.

Dr. So, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa, explained that ticagrelor is a first-line antiplatelet agent for patients with acute coronary syndromes (ACS), but around 10% of patients presenting with ACS require CABG surgery.

A major concern among patients requiring bypass surgery is perioperative bleeding, and it has been shown that patients undergoing urgent bypass within 24 hours of the last dose of ticagrelor have increased mortality. Accordingly, guidelines suggest a waiting period for patients not requiring urgent bypass surgery, Dr. So noted.

Current North American guidelines suggest a waiting period of at least 5 days after stopping ticagrelor before bypass surgery. In contrast, the updated European and Japanese guidelines suggest a waiting period of 3 days.

Dr. So noted that all of the guidelines are based on cohort studies and pharmacodynamic studies, with no randomized evidence. Pharmacodynamic studies have shown that at 48 hours after the last dose of ticagrelor, the level of platelet inhibition drops to the same levels seen with long-term treatment with clopidogrel, a weaker antiplatelet drug, and after 120 hours (5 days) the effect has completely worn off.

Dr. So concluded that these new results from the RAPID CABG trial “may influence future iterations of North American guidelines with reduced waiting prior to bypass surgery” for patients receiving ticagrelor, and “they could also strengthen the level of evidence in European and Asian guidelines.”

Designated discussant of the RAPID CABG trial, Roxana Mehran, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, said this was a “very important study,” being the only randomized trial to look at this issue to date.

Dr. Mehran noted that the results showed a similar number of major life-threatening bleeding events in the early and delayed groups and met the noninferiority endpoint, but she pointed out that the trial had a small sample size and a small number of events. “Therefore, larger trials are needed to verify these important and encouraging results.”

However, she concluded that these results should be considered in decisions about the timing of bypass surgery in patients receiving ticagrelor. “I will be changing my practice and sending patients earlier based on this data,” she said.

 RAPID CABG

RAPID CABG was a physician-initiated multicenter randomized study evaluating the safety of early surgery at 2-3 days after ticagrelor cessation, compared with a delay of 5-7 days among patients presenting with ACS who required nonemergency CABG surgery.

The study enrolled 143 patients with ACS who were receiving ticagrelor and needed CABG surgery. Patients with stenting for culprit lesions, those requiring urgent surgery (less than 24 hours after presentation), and those requiring valve surgery were excluded.   

Three patients declined surgery, and several others underwent surgery outside the assigned time window, so the results were based on the per protocol analysis of patients who actually had CABG in the assigned time window: 65 patients in the early CABG group and 58 in the delayed group.

The mean time from last ticagrelor dose to surgery was 3 days in the early group and 6 days in the delayed group.

Platelet reactivity on the VerifyNow test showed more residual antiplatelet activity in the early group, with P2Y12 reaction unit (PRU) levels of 200 (vs. 251 in the delayed group). This test measures the extent of platelet aggregation in the presence of P2Y12-inhibitor drugs, with lower PRU levels showing stronger antiplatelet effects.

The primary outcome of the study was severe or massive bleeding by Universal Definition of Perioperative Bleeding (UDPB) class 3 or 4. This is defined as a blood transfusions of more than 5 units of red blood cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000 mL in the first 12 hours, and reoperation for bleeding.

Results showed that 4.6% of the early-surgery group had a primary outcome bleeding event, compared with 5.2% of the delayed surgery group, meeting the criteria for noninferiority (P = .0253 for noninferiority).

Individual components of the primary endpoint showed three class 3 (severe) bleeding events in both groups and no class 4 (massive) bleeding events in either group.  

In terms of other bleeding outcomes, TIMI CABG bleeding occurred in two patients (3.1%) in the early-surgery group vs. no patients in the delayed group; BARC 4 bleeding occurred in two patients (3.1%) in the early group versus none in the delayed group, and there were no BARC 5 bleeding events in either group.

In the intention-to-treat analysis, ischemic events before surgery occurred in six patients (8.7%) in the delayed group (one myocardial infarction, four cases of recurrent ischemia, and one ventricular tachycardia) versus none in the early group.

Cumulative 6-month ischemic events occurred in nine patients (13.0%) in the delayed group vs. four patients (5.6%) in the early group, the difference being driven by nonfatal MI and recurrent ischemia.  

There were no cardiovascular deaths in either group and one all-cause death in both groups.

Patients undergoing early surgery also had a shorter hospitalization, with a median length of stay of 9 days versus 12 days in the delayed group.

Larger trial needed

Commenting on the RAPID CABG study at an AHA press conference, Joanna Chikwe, MD, chair of the cardiac surgery department at Cedars-Sinai Medical Center, Los Angeles, said the results were in line with her practice.

“These results confirm what I already think is safe,” she said. “I’m comfortable going within 48 hours. But we individualize our approach, so it was helpful that the study investigators included platelet reactivity data. The interesting thing for me in this study was the number of adverse events in patients who waited longer.” 

Dr. Chikwe said her top-line message was that “Surgery looked incredibly safe; there was amazingly low mortality. And if a patient has an indication for surgery, waiting does not serve you well.”

However, she also cautioned that the trial was somewhat underpowered, with a small number of events that drove the primary outcome, leading to some uncertainty on the results.

“The RAPID trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Dr. Chikwe noted.  

She added that clinical trials in cardiac surgery are driven by inherent challenges. “Cardiac surgery is not very common, and it is hard to recruit patients into these trials, so you are generally tied to a small number of patients, and you therefore have to be extremely thoughtful about the study design. It is almost a given that you will need to use surrogate endpoints, and the choice of the surrogate endpoint can determine which way the trial goes.”

The RAPID CABG study was funded by the Canadian Institutes of Health Research. Dr. So reports research support, consultancy, or speaker’s fees from AggreDyne, Roche Diagnostics, Fujimori Kogyo, and AstraZeneca Canada. Dr. Mehran reports that her institution has received significant trial funding from AstraZeneca (the manufacturer of ticagrelor).  

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

Patients with acute coronary syndromes who have been taking the antiplatelet medication, ticagrelor, and who need coronary artery bypass surgery (CABG) may be able to safely have the procedure earlier than typically recommended, a new randomized trial suggests.

The RAPID CABG trial found that early surgery 2-3 days after ticagrelor cessation was noninferior in incurring severe or massive perioperative bleeding, compared with waiting 5-7 days. There was also no significant difference in TIMI CABG or Bleeding Academic Research Consortium (BARC) type 4 or 5 bleeding.

Patients in the delayed group had a numerically higher number of ischemic events requiring earlier surgery and had a longer hospital stay.

The study was presented at the American Heart Association scientific sessions.

“RAPID CABG is the first and only randomized controlled trial evaluating the safety of early surgery in patients taking ticagrelor,” said lead investigator Derek So, MD.

Dr. So, a cardiologist at the University of Ottawa Heart Institute and a professor at the University of Ottawa, explained that ticagrelor is a first-line antiplatelet agent for patients with acute coronary syndromes (ACS), but around 10% of patients presenting with ACS require CABG surgery.

A major concern among patients requiring bypass surgery is perioperative bleeding, and it has been shown that patients undergoing urgent bypass within 24 hours of the last dose of ticagrelor have increased mortality. Accordingly, guidelines suggest a waiting period for patients not requiring urgent bypass surgery, Dr. So noted.

Current North American guidelines suggest a waiting period of at least 5 days after stopping ticagrelor before bypass surgery. In contrast, the updated European and Japanese guidelines suggest a waiting period of 3 days.

Dr. So noted that all of the guidelines are based on cohort studies and pharmacodynamic studies, with no randomized evidence. Pharmacodynamic studies have shown that at 48 hours after the last dose of ticagrelor, the level of platelet inhibition drops to the same levels seen with long-term treatment with clopidogrel, a weaker antiplatelet drug, and after 120 hours (5 days) the effect has completely worn off.

Dr. So concluded that these new results from the RAPID CABG trial “may influence future iterations of North American guidelines with reduced waiting prior to bypass surgery” for patients receiving ticagrelor, and “they could also strengthen the level of evidence in European and Asian guidelines.”

Designated discussant of the RAPID CABG trial, Roxana Mehran, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York, said this was a “very important study,” being the only randomized trial to look at this issue to date.

Dr. Mehran noted that the results showed a similar number of major life-threatening bleeding events in the early and delayed groups and met the noninferiority endpoint, but she pointed out that the trial had a small sample size and a small number of events. “Therefore, larger trials are needed to verify these important and encouraging results.”

However, she concluded that these results should be considered in decisions about the timing of bypass surgery in patients receiving ticagrelor. “I will be changing my practice and sending patients earlier based on this data,” she said.

 RAPID CABG

RAPID CABG was a physician-initiated multicenter randomized study evaluating the safety of early surgery at 2-3 days after ticagrelor cessation, compared with a delay of 5-7 days among patients presenting with ACS who required nonemergency CABG surgery.

The study enrolled 143 patients with ACS who were receiving ticagrelor and needed CABG surgery. Patients with stenting for culprit lesions, those requiring urgent surgery (less than 24 hours after presentation), and those requiring valve surgery were excluded.   

Three patients declined surgery, and several others underwent surgery outside the assigned time window, so the results were based on the per protocol analysis of patients who actually had CABG in the assigned time window: 65 patients in the early CABG group and 58 in the delayed group.

The mean time from last ticagrelor dose to surgery was 3 days in the early group and 6 days in the delayed group.

Platelet reactivity on the VerifyNow test showed more residual antiplatelet activity in the early group, with P2Y12 reaction unit (PRU) levels of 200 (vs. 251 in the delayed group). This test measures the extent of platelet aggregation in the presence of P2Y12-inhibitor drugs, with lower PRU levels showing stronger antiplatelet effects.

The primary outcome of the study was severe or massive bleeding by Universal Definition of Perioperative Bleeding (UDPB) class 3 or 4. This is defined as a blood transfusions of more than 5 units of red blood cells or plasma within 24 hours of surgical closure, chest tube drainage of over 1,000 mL in the first 12 hours, and reoperation for bleeding.

Results showed that 4.6% of the early-surgery group had a primary outcome bleeding event, compared with 5.2% of the delayed surgery group, meeting the criteria for noninferiority (P = .0253 for noninferiority).

Individual components of the primary endpoint showed three class 3 (severe) bleeding events in both groups and no class 4 (massive) bleeding events in either group.  

In terms of other bleeding outcomes, TIMI CABG bleeding occurred in two patients (3.1%) in the early-surgery group vs. no patients in the delayed group; BARC 4 bleeding occurred in two patients (3.1%) in the early group versus none in the delayed group, and there were no BARC 5 bleeding events in either group.

In the intention-to-treat analysis, ischemic events before surgery occurred in six patients (8.7%) in the delayed group (one myocardial infarction, four cases of recurrent ischemia, and one ventricular tachycardia) versus none in the early group.

Cumulative 6-month ischemic events occurred in nine patients (13.0%) in the delayed group vs. four patients (5.6%) in the early group, the difference being driven by nonfatal MI and recurrent ischemia.  

There were no cardiovascular deaths in either group and one all-cause death in both groups.

Patients undergoing early surgery also had a shorter hospitalization, with a median length of stay of 9 days versus 12 days in the delayed group.

Larger trial needed

Commenting on the RAPID CABG study at an AHA press conference, Joanna Chikwe, MD, chair of the cardiac surgery department at Cedars-Sinai Medical Center, Los Angeles, said the results were in line with her practice.

“These results confirm what I already think is safe,” she said. “I’m comfortable going within 48 hours. But we individualize our approach, so it was helpful that the study investigators included platelet reactivity data. The interesting thing for me in this study was the number of adverse events in patients who waited longer.” 

Dr. Chikwe said her top-line message was that “Surgery looked incredibly safe; there was amazingly low mortality. And if a patient has an indication for surgery, waiting does not serve you well.”

However, she also cautioned that the trial was somewhat underpowered, with a small number of events that drove the primary outcome, leading to some uncertainty on the results.

“The RAPID trial was helpful, and although it confirms my practice, I think physicians may want to see a larger-powered trial to be convincingly compelled that they should change their practice,” Dr. Chikwe noted.  

She added that clinical trials in cardiac surgery are driven by inherent challenges. “Cardiac surgery is not very common, and it is hard to recruit patients into these trials, so you are generally tied to a small number of patients, and you therefore have to be extremely thoughtful about the study design. It is almost a given that you will need to use surrogate endpoints, and the choice of the surrogate endpoint can determine which way the trial goes.”

The RAPID CABG study was funded by the Canadian Institutes of Health Research. Dr. So reports research support, consultancy, or speaker’s fees from AggreDyne, Roche Diagnostics, Fujimori Kogyo, and AstraZeneca Canada. Dr. Mehran reports that her institution has received significant trial funding from AstraZeneca (the manufacturer of ticagrelor).  

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

Tricuspid valve repair at the time of mitral valve surgery reduces tricuspid regurgitation progression, but at the cost of more than a fivefold increase in permanent pacemakers, results of a new Cardiothoracic Surgical Trials Network study show.

The results were presented during the opening late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.

Tricuspid regurgitation (TR) is common among patients undergoing mitral valve surgery, and there’s broad agreement to intervene when a patient has severe TR. There’s uncertainty, however, about the management of moderate or less TR during mitral valve surgery, which is reflected in current guidelines on the basis of observational data, explained coprimary investigator James Gammie, MD, codirector and surgical director of the Johns Hopkins Heart and Vascular Institute, Baltimore. As a result, rates of concomitant tricuspid-mitral surgery range from 5% to 75% at various centers.

To help fill the gap, Dr. Gammie and colleagues screened 5,208 patients at 29 centers in the United States, Canada, and Germany undergoing surgery for degenerative mitral regurgitation, and randomly assigned 401 patients (75% male) to mitral valve surgery alone or with tricuspid annuloplasty.

Patients had either moderate TR (37%) or less than moderate TR with a dilated tricuspid annulus of at least 40 mm or at least 21 mm/m² indexed for body surface area. Importantly, there was a uniform surgical approach using undersized (26-30 mm) rigid nonplanar annuloplasty rings to repair the tricuspid valve, he said.

The study’s primary outcome of treatment failure at 2 years was defined as the composite of death, reoperation for TR, or progression of TR from baseline by 2 grades or severe TR.

The primary endpoint occurred in 10.2% of patients who underwent mitral valve surgery alone and 3.9% who underwent concomitant tricuspid annuloplasty (relative risk, 0.37; 95% confidence interval, 0.16-0.86; P = .02).

The endpoint was driven exclusively by less TR progression in the annuloplasty group, with no TR reoperations in either group, observed Dr. Gammie. At 2 years, just 0.6% of the annuloplasty group had severe TR, compared with 5.6% of the surgery-alone group.

The rate of permanent pacemaker implantations, however, jumped from 2.5% with surgery alone to 14.1% with concomitant tricuspid annuloplasty (rate ratio, 5.75; 95% CI, 2.27-14.60). More than half of pacemakers were placed during the first 2 days after surgery.

There was no between-group difference in 2-year rates of all-cause mortality, major adverse cardiac and cerebrovascular events, readmission, quality of life, or functional status.

Less than moderate TR

In a post hoc analysis stratified by baseline TR severity, treatment failure was significantly less common with surgery plus tricuspid annuloplasty among patients with moderate TR (4.5% vs. 18.1%) but not among those with less than moderate TR and tricuspid annular dilation (3.4% vs. 6.1%).

Although the trial was not powered for the subgroup analysis, “these results call into question the idea that less than moderate TR with annular dilation should be an indication for tricuspid valve repair,” Dr. Gammie told this news organization.

“I did not repair the tricuspid valve in the setting of less than moderate TR before the trial, and my practice won’t change; but it will be based on much better evidence,” he added. “Of course, long-term data from our trial will be of great interest.”

Discussant Joseph Woo, MD, chair of surgery at Stanford (Calif.) University, congratulated the authors on a “landmark trial” that addresses a highly relevant problem without a clear-cut indication.

In the 2020 AHA/American College of Cardiology heart valve disease guideline, tricuspid valve surgery is a class I recommendation when there’s severe TR (stages C and D) and left-sided valve surgery but a class IIa recommendation in patients with progressive TR (stage B) with an annular dilation of at least 40 mm.

“The interesting findings in this study include that moderate TR was only 37% of the enrolled patients, and only 97% of the patients with degenerative MR received a mitral valve repair,” Dr. Woo said. “This level of mitral valve repair is perhaps lower than what we might expect at these centers and lower, certainly, than what the AHA/ACC guidelines recommend for surgery on asymptomatic severe mitral regurgitation.”

Panelist Roxanna Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York said, “What I was struck by is that we, as clinicians, believe that if you fix the mitral valve, maybe the tricuspid regurgitation will improve. And it seems like that is not what’s happening, and I think that’s a big takeaway.”

Session comoderator Joanna Chikwe, MD, head of cardiac surgery at Cedars-Sinai Medical Center, Los Angeles, said, “I think we can all agree that severe tricuspid regurgitation is a disaster for patients, and I think the fact the trial is designed for an additional 5 years’ follow-up will hopefully give us some insights into the clinical impact of severe tricuspid regurgitation.”

For now, “a back of the envelope calculation suggests that, for every 20 patients with moderate tricuspid regurgitation who we repair the tricuspid valve in, we would prevent severe tricuspid valve regurgitation in 1 at the price of pacemakers in 2,” she said.

Dr. Chikwe said in an interview that “transcatheter tricuspid repair is increasingly helping these patients, but if you could avoid it with a technique that doesn’t cause incremental harm beyond, perhaps, the need for pacemakers, then this is helpful data that supports that approach.”

The pacemaker burden is not negligible, she said, but also not surprising to surgeons. “If you look at national practice of mitral-tricuspid surgery, it’s about 15% after that, and it’s simply because the conduction tissue is so close to the tricuspid annulus.”

Pacemaker implantation rates, like those for concomitant tricuspid-mitral surgery, are also highly variable, and in some single-center series only around 2%, Dr. Chikwe said. “So that suggests there are technical approaches that can minimize the pacemaker rate [such as] being extremely careful to avoid suture placement around the area of the conduction tissues.”

For some the trade-off between reduced TR progression and the risk of a permanent pacemaker is worth it. “But the fact that the trial didn’t show a difference in survival, a difference in symptoms or quality of life, might suggest that patients you anticipated were high risk for surgery or didn’t have a longer projected survival aren’t going to benefit from what is quite an aggressive surgical approach,” Dr. Chikwe said.

In an accompanying editorial, Dr. Chikwe and Mario Gaudino, MD, of Weill Cornell Medicine, New York, also point out that the “very dynamic nature of tricuspid regurgitation and wide variability in assessing tricuspid annular dilatation are additional compelling reasons to leave lesser regurgitation alone.”

Julia Grapsa, MD, PhD, Kings College and tricuspid service lead at Guys and St. Thomas NHS, London, also pointed to the need for longer-term follow-up but said increased use of imaging markers is also needed to help pinpoint TR progression in these patients. “For the moment, the results should remind imagers and clinicians to refer patients earlier.”

“As a valvular heart physician, I see more and more patients coming in with significant severe tricuspid regurgitation post–mitral valve surgery and because of the time that’s passed, there’s dysfunction of the right heart, the left heart, and it’s very hard to suggest an operation because they’re at high risk,” she said. “So we’re discussing with these patients whether to do an intervention or medical management.”

“Now, with this study, and the pending longer follow-up by the authors, I’m optimistic that the class II recommendation will be class I in order to help our patients treat tricuspid regurgitation earlier than late,” said Dr. Grapsa, who is also editor-in-chief of JACC: Case Reports.

The study was funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research. Dr. Gammie reports a consultant/stockholder relationship with Edwards Lifesciences. Dr. Grapsa reports no conflicts of interest. Dr. Chikwe reports that as coprincipal investigator/study director of NCT 05051033 (an NHLBI-sponsored Cardiothoracic Surgical Trials Network trial), she collaborates with several of the study authors.
 

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

Tricuspid valve repair at the time of mitral valve surgery reduces tricuspid regurgitation progression, but at the cost of more than a fivefold increase in permanent pacemakers, results of a new Cardiothoracic Surgical Trials Network study show.

The results were presented during the opening late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.

Tricuspid regurgitation (TR) is common among patients undergoing mitral valve surgery, and there’s broad agreement to intervene when a patient has severe TR. There’s uncertainty, however, about the management of moderate or less TR during mitral valve surgery, which is reflected in current guidelines on the basis of observational data, explained coprimary investigator James Gammie, MD, codirector and surgical director of the Johns Hopkins Heart and Vascular Institute, Baltimore. As a result, rates of concomitant tricuspid-mitral surgery range from 5% to 75% at various centers.

To help fill the gap, Dr. Gammie and colleagues screened 5,208 patients at 29 centers in the United States, Canada, and Germany undergoing surgery for degenerative mitral regurgitation, and randomly assigned 401 patients (75% male) to mitral valve surgery alone or with tricuspid annuloplasty.

Patients had either moderate TR (37%) or less than moderate TR with a dilated tricuspid annulus of at least 40 mm or at least 21 mm/m² indexed for body surface area. Importantly, there was a uniform surgical approach using undersized (26-30 mm) rigid nonplanar annuloplasty rings to repair the tricuspid valve, he said.

The study’s primary outcome of treatment failure at 2 years was defined as the composite of death, reoperation for TR, or progression of TR from baseline by 2 grades or severe TR.

The primary endpoint occurred in 10.2% of patients who underwent mitral valve surgery alone and 3.9% who underwent concomitant tricuspid annuloplasty (relative risk, 0.37; 95% confidence interval, 0.16-0.86; P = .02).

The endpoint was driven exclusively by less TR progression in the annuloplasty group, with no TR reoperations in either group, observed Dr. Gammie. At 2 years, just 0.6% of the annuloplasty group had severe TR, compared with 5.6% of the surgery-alone group.

The rate of permanent pacemaker implantations, however, jumped from 2.5% with surgery alone to 14.1% with concomitant tricuspid annuloplasty (rate ratio, 5.75; 95% CI, 2.27-14.60). More than half of pacemakers were placed during the first 2 days after surgery.

There was no between-group difference in 2-year rates of all-cause mortality, major adverse cardiac and cerebrovascular events, readmission, quality of life, or functional status.

Less than moderate TR

In a post hoc analysis stratified by baseline TR severity, treatment failure was significantly less common with surgery plus tricuspid annuloplasty among patients with moderate TR (4.5% vs. 18.1%) but not among those with less than moderate TR and tricuspid annular dilation (3.4% vs. 6.1%).

Although the trial was not powered for the subgroup analysis, “these results call into question the idea that less than moderate TR with annular dilation should be an indication for tricuspid valve repair,” Dr. Gammie told this news organization.

“I did not repair the tricuspid valve in the setting of less than moderate TR before the trial, and my practice won’t change; but it will be based on much better evidence,” he added. “Of course, long-term data from our trial will be of great interest.”

Discussant Joseph Woo, MD, chair of surgery at Stanford (Calif.) University, congratulated the authors on a “landmark trial” that addresses a highly relevant problem without a clear-cut indication.

In the 2020 AHA/American College of Cardiology heart valve disease guideline, tricuspid valve surgery is a class I recommendation when there’s severe TR (stages C and D) and left-sided valve surgery but a class IIa recommendation in patients with progressive TR (stage B) with an annular dilation of at least 40 mm.

“The interesting findings in this study include that moderate TR was only 37% of the enrolled patients, and only 97% of the patients with degenerative MR received a mitral valve repair,” Dr. Woo said. “This level of mitral valve repair is perhaps lower than what we might expect at these centers and lower, certainly, than what the AHA/ACC guidelines recommend for surgery on asymptomatic severe mitral regurgitation.”

Panelist Roxanna Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York said, “What I was struck by is that we, as clinicians, believe that if you fix the mitral valve, maybe the tricuspid regurgitation will improve. And it seems like that is not what’s happening, and I think that’s a big takeaway.”

Session comoderator Joanna Chikwe, MD, head of cardiac surgery at Cedars-Sinai Medical Center, Los Angeles, said, “I think we can all agree that severe tricuspid regurgitation is a disaster for patients, and I think the fact the trial is designed for an additional 5 years’ follow-up will hopefully give us some insights into the clinical impact of severe tricuspid regurgitation.”

For now, “a back of the envelope calculation suggests that, for every 20 patients with moderate tricuspid regurgitation who we repair the tricuspid valve in, we would prevent severe tricuspid valve regurgitation in 1 at the price of pacemakers in 2,” she said.

Dr. Chikwe said in an interview that “transcatheter tricuspid repair is increasingly helping these patients, but if you could avoid it with a technique that doesn’t cause incremental harm beyond, perhaps, the need for pacemakers, then this is helpful data that supports that approach.”

The pacemaker burden is not negligible, she said, but also not surprising to surgeons. “If you look at national practice of mitral-tricuspid surgery, it’s about 15% after that, and it’s simply because the conduction tissue is so close to the tricuspid annulus.”

Pacemaker implantation rates, like those for concomitant tricuspid-mitral surgery, are also highly variable, and in some single-center series only around 2%, Dr. Chikwe said. “So that suggests there are technical approaches that can minimize the pacemaker rate [such as] being extremely careful to avoid suture placement around the area of the conduction tissues.”

For some the trade-off between reduced TR progression and the risk of a permanent pacemaker is worth it. “But the fact that the trial didn’t show a difference in survival, a difference in symptoms or quality of life, might suggest that patients you anticipated were high risk for surgery or didn’t have a longer projected survival aren’t going to benefit from what is quite an aggressive surgical approach,” Dr. Chikwe said.

In an accompanying editorial, Dr. Chikwe and Mario Gaudino, MD, of Weill Cornell Medicine, New York, also point out that the “very dynamic nature of tricuspid regurgitation and wide variability in assessing tricuspid annular dilatation are additional compelling reasons to leave lesser regurgitation alone.”

Julia Grapsa, MD, PhD, Kings College and tricuspid service lead at Guys and St. Thomas NHS, London, also pointed to the need for longer-term follow-up but said increased use of imaging markers is also needed to help pinpoint TR progression in these patients. “For the moment, the results should remind imagers and clinicians to refer patients earlier.”

“As a valvular heart physician, I see more and more patients coming in with significant severe tricuspid regurgitation post–mitral valve surgery and because of the time that’s passed, there’s dysfunction of the right heart, the left heart, and it’s very hard to suggest an operation because they’re at high risk,” she said. “So we’re discussing with these patients whether to do an intervention or medical management.”

“Now, with this study, and the pending longer follow-up by the authors, I’m optimistic that the class II recommendation will be class I in order to help our patients treat tricuspid regurgitation earlier than late,” said Dr. Grapsa, who is also editor-in-chief of JACC: Case Reports.

The study was funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research. Dr. Gammie reports a consultant/stockholder relationship with Edwards Lifesciences. Dr. Grapsa reports no conflicts of interest. Dr. Chikwe reports that as coprincipal investigator/study director of NCT 05051033 (an NHLBI-sponsored Cardiothoracic Surgical Trials Network trial), she collaborates with several of the study authors.
 

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

Tricuspid valve repair at the time of mitral valve surgery reduces tricuspid regurgitation progression, but at the cost of more than a fivefold increase in permanent pacemakers, results of a new Cardiothoracic Surgical Trials Network study show.

The results were presented during the opening late-breaking science session at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.

Tricuspid regurgitation (TR) is common among patients undergoing mitral valve surgery, and there’s broad agreement to intervene when a patient has severe TR. There’s uncertainty, however, about the management of moderate or less TR during mitral valve surgery, which is reflected in current guidelines on the basis of observational data, explained coprimary investigator James Gammie, MD, codirector and surgical director of the Johns Hopkins Heart and Vascular Institute, Baltimore. As a result, rates of concomitant tricuspid-mitral surgery range from 5% to 75% at various centers.

To help fill the gap, Dr. Gammie and colleagues screened 5,208 patients at 29 centers in the United States, Canada, and Germany undergoing surgery for degenerative mitral regurgitation, and randomly assigned 401 patients (75% male) to mitral valve surgery alone or with tricuspid annuloplasty.

Patients had either moderate TR (37%) or less than moderate TR with a dilated tricuspid annulus of at least 40 mm or at least 21 mm/m² indexed for body surface area. Importantly, there was a uniform surgical approach using undersized (26-30 mm) rigid nonplanar annuloplasty rings to repair the tricuspid valve, he said.

The study’s primary outcome of treatment failure at 2 years was defined as the composite of death, reoperation for TR, or progression of TR from baseline by 2 grades or severe TR.

The primary endpoint occurred in 10.2% of patients who underwent mitral valve surgery alone and 3.9% who underwent concomitant tricuspid annuloplasty (relative risk, 0.37; 95% confidence interval, 0.16-0.86; P = .02).

The endpoint was driven exclusively by less TR progression in the annuloplasty group, with no TR reoperations in either group, observed Dr. Gammie. At 2 years, just 0.6% of the annuloplasty group had severe TR, compared with 5.6% of the surgery-alone group.

The rate of permanent pacemaker implantations, however, jumped from 2.5% with surgery alone to 14.1% with concomitant tricuspid annuloplasty (rate ratio, 5.75; 95% CI, 2.27-14.60). More than half of pacemakers were placed during the first 2 days after surgery.

There was no between-group difference in 2-year rates of all-cause mortality, major adverse cardiac and cerebrovascular events, readmission, quality of life, or functional status.

Less than moderate TR

In a post hoc analysis stratified by baseline TR severity, treatment failure was significantly less common with surgery plus tricuspid annuloplasty among patients with moderate TR (4.5% vs. 18.1%) but not among those with less than moderate TR and tricuspid annular dilation (3.4% vs. 6.1%).

Although the trial was not powered for the subgroup analysis, “these results call into question the idea that less than moderate TR with annular dilation should be an indication for tricuspid valve repair,” Dr. Gammie told this news organization.

“I did not repair the tricuspid valve in the setting of less than moderate TR before the trial, and my practice won’t change; but it will be based on much better evidence,” he added. “Of course, long-term data from our trial will be of great interest.”

Discussant Joseph Woo, MD, chair of surgery at Stanford (Calif.) University, congratulated the authors on a “landmark trial” that addresses a highly relevant problem without a clear-cut indication.

In the 2020 AHA/American College of Cardiology heart valve disease guideline, tricuspid valve surgery is a class I recommendation when there’s severe TR (stages C and D) and left-sided valve surgery but a class IIa recommendation in patients with progressive TR (stage B) with an annular dilation of at least 40 mm.

“The interesting findings in this study include that moderate TR was only 37% of the enrolled patients, and only 97% of the patients with degenerative MR received a mitral valve repair,” Dr. Woo said. “This level of mitral valve repair is perhaps lower than what we might expect at these centers and lower, certainly, than what the AHA/ACC guidelines recommend for surgery on asymptomatic severe mitral regurgitation.”

Panelist Roxanna Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York said, “What I was struck by is that we, as clinicians, believe that if you fix the mitral valve, maybe the tricuspid regurgitation will improve. And it seems like that is not what’s happening, and I think that’s a big takeaway.”

Session comoderator Joanna Chikwe, MD, head of cardiac surgery at Cedars-Sinai Medical Center, Los Angeles, said, “I think we can all agree that severe tricuspid regurgitation is a disaster for patients, and I think the fact the trial is designed for an additional 5 years’ follow-up will hopefully give us some insights into the clinical impact of severe tricuspid regurgitation.”

For now, “a back of the envelope calculation suggests that, for every 20 patients with moderate tricuspid regurgitation who we repair the tricuspid valve in, we would prevent severe tricuspid valve regurgitation in 1 at the price of pacemakers in 2,” she said.

Dr. Chikwe said in an interview that “transcatheter tricuspid repair is increasingly helping these patients, but if you could avoid it with a technique that doesn’t cause incremental harm beyond, perhaps, the need for pacemakers, then this is helpful data that supports that approach.”

The pacemaker burden is not negligible, she said, but also not surprising to surgeons. “If you look at national practice of mitral-tricuspid surgery, it’s about 15% after that, and it’s simply because the conduction tissue is so close to the tricuspid annulus.”

Pacemaker implantation rates, like those for concomitant tricuspid-mitral surgery, are also highly variable, and in some single-center series only around 2%, Dr. Chikwe said. “So that suggests there are technical approaches that can minimize the pacemaker rate [such as] being extremely careful to avoid suture placement around the area of the conduction tissues.”

For some the trade-off between reduced TR progression and the risk of a permanent pacemaker is worth it. “But the fact that the trial didn’t show a difference in survival, a difference in symptoms or quality of life, might suggest that patients you anticipated were high risk for surgery or didn’t have a longer projected survival aren’t going to benefit from what is quite an aggressive surgical approach,” Dr. Chikwe said.

In an accompanying editorial, Dr. Chikwe and Mario Gaudino, MD, of Weill Cornell Medicine, New York, also point out that the “very dynamic nature of tricuspid regurgitation and wide variability in assessing tricuspid annular dilatation are additional compelling reasons to leave lesser regurgitation alone.”

Julia Grapsa, MD, PhD, Kings College and tricuspid service lead at Guys and St. Thomas NHS, London, also pointed to the need for longer-term follow-up but said increased use of imaging markers is also needed to help pinpoint TR progression in these patients. “For the moment, the results should remind imagers and clinicians to refer patients earlier.”

“As a valvular heart physician, I see more and more patients coming in with significant severe tricuspid regurgitation post–mitral valve surgery and because of the time that’s passed, there’s dysfunction of the right heart, the left heart, and it’s very hard to suggest an operation because they’re at high risk,” she said. “So we’re discussing with these patients whether to do an intervention or medical management.”

“Now, with this study, and the pending longer follow-up by the authors, I’m optimistic that the class II recommendation will be class I in order to help our patients treat tricuspid regurgitation earlier than late,” said Dr. Grapsa, who is also editor-in-chief of JACC: Case Reports.

The study was funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research. Dr. Gammie reports a consultant/stockholder relationship with Edwards Lifesciences. Dr. Grapsa reports no conflicts of interest. Dr. Chikwe reports that as coprincipal investigator/study director of NCT 05051033 (an NHLBI-sponsored Cardiothoracic Surgical Trials Network trial), she collaborates with several of the study authors.
 

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

A novel, stent-shaped device that provides external buttressing to saphenous vein grafts placed during coronary artery bypass surgery was safe, but failed to improve 12-month patency of vein grafts, in a prospective study with 224 patients.

Despite the neutral result, “we are cautiously optimistic” about the prospects for the device to reduce the risk for failure of coronary vein grafts caused by intimal hyperplasia of the internal lining of the vein graft that leads to graft occlusion, said John D. Puskas, MD, lead investigator of the study, who reported the results at the American Heart Association scientific sessions.

In the trial, called VEST, each buttressed vein graft was compared with a similar, unbuttressed graft in the same patient. Perhaps the biggest issue faced by the study was the unexpectedly high 42% rate of vein-graft occlusion or diffuse disease seen in the studied grafts 12 months after placement. This rate included both the vein grafts placed within the external buttressing device and control vein grafts that underwent the same postharvest preparation but weren’t placed within an external sheath, which is formed from woven cobalt chromium wire.

Dr. Puskas attributed this high failure rate to the need to remove all adventitia tissue and fat from the harvested saphenous vein segments before grafting, a step required to allow the vein conduit to fit inside the wire sheath. The potential exists to further optimize this step, he said in an interview.

“I was very surprised by the low 12-month patency rates” in both treatment arms of the study, commented Joanna Chikwe, MD, chair of cardiac surgery at Cedars-Sinai Medical Center in Los Angeles.

External scaffold to counter blood pressure

The concept behind the external buttressing sheath is that the walls of saphenous vein grafts are not structured to accommodate arterial blood pressure, and over time this pressure produces accelerated atherosclerotic changes and premature occlusion and graft failure. The external support is supposed to impede vein wall dilatation, reduce irregularities of the inner lumen surface, and improve hemodynamics and shear stress.

The VEST trial ran at 14 U.S. and 3 Canadian centers and enrolled 224 patients scheduled for coronary artery bypass grafting with planned use of at least two saphenous vein grafts, along with an internal mammary artery graft for the left anterior descending coronary artery. The patients averaged 66 years of age, 21% were women, and 51% had diabetes.

All patients successfully underwent their surgery, with 203 returning after 12 months for their primary follow-up examination by intravascular ultrasound. However, because of the high rate of vein occlusion or development of diffuse intragraft disease, successful intravascular ultrasound (IVUS) examination of both vein grafts occurred in only 113 patients.

The IVUS examinations showed that the study’s primary endpoint, the intimal hyperplasia area in all 224 patients who received vein grafts, averaged 5.11 mm² in the grafts placed within the wire sleeve and 5.79 mm² for control grafts not placed in the wire sheath, a difference that fell short of significance (P = .072). However, in a sensitivity analysis that focused on only the 113 patients who had both vein grafts successfully assayed by IVUS, the average area of intimal hyperplasia was 4.58 mm² in the grafts within a wire sheath and 5.12 mm² in the control grafts, a significant difference (P = .043).

The combined rate of major adverse cardiovascular events after 12 months was 7%, including a 2% mortality rate, a 3% stroke rate, and 3% rate of Mis, outcomes that suggested “no safety signals,” said Dr. Puskas, chair of cardiovascular surgery at Mount Sinai St. Luke’s in New York.

Although a large body of evidence has shown the superiority of arterial grafts for long-term graft patency, vein grafts have many advantages that have maintained them as the most widely used conduits worldwide for coronary artery bypass surgery, Dr. Puskas said.

Saphenous vein segments are readily available from patients and easy to harvest; they nicely conform to the coronary arteries that require bypass, rarely leak, are easy to work with, and can successfully hold stitches. Surgeons performing coronary artery bypass are unlikely to abandon vein grafts anytime soon, which makes improving the performance of vein grafts a priority, Dr. Puskas said.

The study was sponsored by Vascular Graft Solutions, the company developing the venous graft external support. Dr. Puskas and Dr. Chikwe had no disclosures related to the study.

[email protected]
 

A novel, stent-shaped device that provides external buttressing to saphenous vein grafts placed during coronary artery bypass surgery was safe, but failed to improve 12-month patency of vein grafts, in a prospective study with 224 patients.

Despite the neutral result, “we are cautiously optimistic” about the prospects for the device to reduce the risk for failure of coronary vein grafts caused by intimal hyperplasia of the internal lining of the vein graft that leads to graft occlusion, said John D. Puskas, MD, lead investigator of the study, who reported the results at the American Heart Association scientific sessions.

In the trial, called VEST, each buttressed vein graft was compared with a similar, unbuttressed graft in the same patient. Perhaps the biggest issue faced by the study was the unexpectedly high 42% rate of vein-graft occlusion or diffuse disease seen in the studied grafts 12 months after placement. This rate included both the vein grafts placed within the external buttressing device and control vein grafts that underwent the same postharvest preparation but weren’t placed within an external sheath, which is formed from woven cobalt chromium wire.

Dr. Puskas attributed this high failure rate to the need to remove all adventitia tissue and fat from the harvested saphenous vein segments before grafting, a step required to allow the vein conduit to fit inside the wire sheath. The potential exists to further optimize this step, he said in an interview.

“I was very surprised by the low 12-month patency rates” in both treatment arms of the study, commented Joanna Chikwe, MD, chair of cardiac surgery at Cedars-Sinai Medical Center in Los Angeles.

External scaffold to counter blood pressure

The concept behind the external buttressing sheath is that the walls of saphenous vein grafts are not structured to accommodate arterial blood pressure, and over time this pressure produces accelerated atherosclerotic changes and premature occlusion and graft failure. The external support is supposed to impede vein wall dilatation, reduce irregularities of the inner lumen surface, and improve hemodynamics and shear stress.

The VEST trial ran at 14 U.S. and 3 Canadian centers and enrolled 224 patients scheduled for coronary artery bypass grafting with planned use of at least two saphenous vein grafts, along with an internal mammary artery graft for the left anterior descending coronary artery. The patients averaged 66 years of age, 21% were women, and 51% had diabetes.

All patients successfully underwent their surgery, with 203 returning after 12 months for their primary follow-up examination by intravascular ultrasound. However, because of the high rate of vein occlusion or development of diffuse intragraft disease, successful intravascular ultrasound (IVUS) examination of both vein grafts occurred in only 113 patients.

The IVUS examinations showed that the study’s primary endpoint, the intimal hyperplasia area in all 224 patients who received vein grafts, averaged 5.11 mm² in the grafts placed within the wire sleeve and 5.79 mm² for control grafts not placed in the wire sheath, a difference that fell short of significance (P = .072). However, in a sensitivity analysis that focused on only the 113 patients who had both vein grafts successfully assayed by IVUS, the average area of intimal hyperplasia was 4.58 mm² in the grafts within a wire sheath and 5.12 mm² in the control grafts, a significant difference (P = .043).

The combined rate of major adverse cardiovascular events after 12 months was 7%, including a 2% mortality rate, a 3% stroke rate, and 3% rate of Mis, outcomes that suggested “no safety signals,” said Dr. Puskas, chair of cardiovascular surgery at Mount Sinai St. Luke’s in New York.

Although a large body of evidence has shown the superiority of arterial grafts for long-term graft patency, vein grafts have many advantages that have maintained them as the most widely used conduits worldwide for coronary artery bypass surgery, Dr. Puskas said.

Saphenous vein segments are readily available from patients and easy to harvest; they nicely conform to the coronary arteries that require bypass, rarely leak, are easy to work with, and can successfully hold stitches. Surgeons performing coronary artery bypass are unlikely to abandon vein grafts anytime soon, which makes improving the performance of vein grafts a priority, Dr. Puskas said.

The study was sponsored by Vascular Graft Solutions, the company developing the venous graft external support. Dr. Puskas and Dr. Chikwe had no disclosures related to the study.

[email protected]
 

A novel, stent-shaped device that provides external buttressing to saphenous vein grafts placed during coronary artery bypass surgery was safe, but failed to improve 12-month patency of vein grafts, in a prospective study with 224 patients.

Despite the neutral result, “we are cautiously optimistic” about the prospects for the device to reduce the risk for failure of coronary vein grafts caused by intimal hyperplasia of the internal lining of the vein graft that leads to graft occlusion, said John D. Puskas, MD, lead investigator of the study, who reported the results at the American Heart Association scientific sessions.

In the trial, called VEST, each buttressed vein graft was compared with a similar, unbuttressed graft in the same patient. Perhaps the biggest issue faced by the study was the unexpectedly high 42% rate of vein-graft occlusion or diffuse disease seen in the studied grafts 12 months after placement. This rate included both the vein grafts placed within the external buttressing device and control vein grafts that underwent the same postharvest preparation but weren’t placed within an external sheath, which is formed from woven cobalt chromium wire.

Dr. Puskas attributed this high failure rate to the need to remove all adventitia tissue and fat from the harvested saphenous vein segments before grafting, a step required to allow the vein conduit to fit inside the wire sheath. The potential exists to further optimize this step, he said in an interview.

“I was very surprised by the low 12-month patency rates” in both treatment arms of the study, commented Joanna Chikwe, MD, chair of cardiac surgery at Cedars-Sinai Medical Center in Los Angeles.

External scaffold to counter blood pressure

The concept behind the external buttressing sheath is that the walls of saphenous vein grafts are not structured to accommodate arterial blood pressure, and over time this pressure produces accelerated atherosclerotic changes and premature occlusion and graft failure. The external support is supposed to impede vein wall dilatation, reduce irregularities of the inner lumen surface, and improve hemodynamics and shear stress.

The VEST trial ran at 14 U.S. and 3 Canadian centers and enrolled 224 patients scheduled for coronary artery bypass grafting with planned use of at least two saphenous vein grafts, along with an internal mammary artery graft for the left anterior descending coronary artery. The patients averaged 66 years of age, 21% were women, and 51% had diabetes.

All patients successfully underwent their surgery, with 203 returning after 12 months for their primary follow-up examination by intravascular ultrasound. However, because of the high rate of vein occlusion or development of diffuse intragraft disease, successful intravascular ultrasound (IVUS) examination of both vein grafts occurred in only 113 patients.

The IVUS examinations showed that the study’s primary endpoint, the intimal hyperplasia area in all 224 patients who received vein grafts, averaged 5.11 mm² in the grafts placed within the wire sleeve and 5.79 mm² for control grafts not placed in the wire sheath, a difference that fell short of significance (P = .072). However, in a sensitivity analysis that focused on only the 113 patients who had both vein grafts successfully assayed by IVUS, the average area of intimal hyperplasia was 4.58 mm² in the grafts within a wire sheath and 5.12 mm² in the control grafts, a significant difference (P = .043).

The combined rate of major adverse cardiovascular events after 12 months was 7%, including a 2% mortality rate, a 3% stroke rate, and 3% rate of Mis, outcomes that suggested “no safety signals,” said Dr. Puskas, chair of cardiovascular surgery at Mount Sinai St. Luke’s in New York.

Although a large body of evidence has shown the superiority of arterial grafts for long-term graft patency, vein grafts have many advantages that have maintained them as the most widely used conduits worldwide for coronary artery bypass surgery, Dr. Puskas said.

Saphenous vein segments are readily available from patients and easy to harvest; they nicely conform to the coronary arteries that require bypass, rarely leak, are easy to work with, and can successfully hold stitches. Surgeons performing coronary artery bypass are unlikely to abandon vein grafts anytime soon, which makes improving the performance of vein grafts a priority, Dr. Puskas said.

The study was sponsored by Vascular Graft Solutions, the company developing the venous graft external support. Dr. Puskas and Dr. Chikwe had no disclosures related to the study.

[email protected]
 

In large-vessel occlusion stroke, results of a randomized trial failed to show noninferiority of direct mechanical thrombectomy using the Solitaire device to the combination of intravenous (IV) thrombolysis plus mechanical thrombectomy.

In the prospective, multicenter trial, the rate of good functional outcome was 57% for patients who underwent direct thrombectomy and 65% among patients who received IV thrombolysis before undergoing thrombectomy. This result failed to demonstrate noninferiority of direct mechanical thrombectomy compared to combination therapy, the researchers conclude.

“Good outcome was high in both treatment arms, with the point estimate in favor of the bridging cohort,” said lead investigator Urs Fischer, MD, co-chair of the stroke center at Inselspital, Bern University Hospital, Switzerland, during his presentation. “Postinterventional reperfusion was very high in both treatment arms and higher in patients with bridging thrombolysis, compared to direct mechanical thrombectomy.”

The findings were presented at the 13th World Stroke Congress (WSC) 2021.
 

Two views of thrombolysis

The value of bridging thrombolysis for patients who undergo mechanical thrombectomy is a matter of debate. One argument is that, for patients with large-vessel occlusion, IV thrombolysis may improve reperfusion before and after thrombectomy and yield better clinical outcomes. The opposing argument is that bridging thrombolysis may increase the risk for distal emboli, delay mechanical thrombectomy, and increase the rate of hemorrhage.

The researchers conducted the SWIFT DIRECT trial to investigate this question. They enrolled patients with acute ischemic stroke due to occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery.

The trial was conducted at 48 sites in seven European countries and Canada. The investigators randomly assigned patients to receive IV alteplase (0.9 mg/kg) plus mechanical thrombectomy with the Solitaire device or to receive direct mechanical thrombectomy with the same device. Treatment was open label, but the assessment of endpoints was blinded.

Investigators assigned 423 patients to treatment, and 408 were included in the full analysis set. Of this group, 201 participants received direct mechanical thrombectomy, and 207 received IV thrombolysis plus thrombectomy. There were three crossovers in each treatment arm.

The primary outcome was functional independence, defined as a Modified Rankin Scale (mRS) score of 0-2, at 90 days. Secondary outcomes included mortality at 90 days, mRS shift, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, successful reperfusion, and symptomatic and asymptomatic intracranial hemorrhage (ICH).
 

Noninferiority not demonstrated

At baseline, patient characteristics were well balanced between the treatment groups. The median age of the patients was 72 years, and about 50% of participants were women. The median NIHSS score was 17 in both arms.

Approximately 57% of patients who underwent direct thrombectomy and 65% of those who received IV thrombolysis plus thrombectomy were functionally independent at 90 days, the primary outcome.

In addition, the researchers found no difference in mRS shift, mortality at 90 days, or change in NIHSS score at 24 hours. Postinterventional reperfusion was very high in both arms and was higher in patients who received IV tissue plasminogen activator, compared with those who received direct mechanical thrombectomy, said Dr. Fischer.

The rate of successful postinterventional reperfusion, however, was higher among patients who received thrombolysis than among those who underwent direct thrombectomy. The rate of symptomatic ICH was 1.5% in the direct thrombectomy group and 4.9% in the thrombolysis-plus-thrombectomy group.
 

New endpoints needed?

The investigators used noninferiority margins of 12%. “This question about the noninferiority margins, that’s a very tricky and difficult one in randomized clinical trials,” said Dr. Fischer. The investigators defined their margin using the 2015 HERMES data because no trials had yet compared direct mechanical thrombectomy and bridging thrombolysis at the time.

The researchers are performing a pooled analysis of all the trials that compared bridging thrombolysis with direct mechanical thrombectomy. “We are therefore looking at several margins, and I think this is the way we should look at these noninferiority margins,” said Dr. Fischer. “There’s not a clear-cut level which you can define.”

Enrollment in the trial was well balanced with respect to gender, which is not always the case in stroke studies, said Kevin Sheth, MD, professor of neurology and neurosurgery at Yale School of Medicine, New Haven, Conn., who commented on the study for this news organization.

The findings indicate that the likelihood of there being a difference between groups on this question is low, said Dr. Sheth. Both groups had large-vessel occlusion, both received thrombectomy, and both achieved reperfusion. But the higher rate of successful reperfusion in the bridging cohort was not reflected in any of the clinical endpoints that the investigators examined.

Observing a difference in this context will require very large trials or different endpoints that are more responsive to the intervention, said Dr. Sheth. “This is going to be a challenge for not just this but for any neuroprotection trial in the future,” he said.

The study was supported by Medtronic. Dr. Fischer has served as a consultant for Medtronic, Stryker, and CSL Behring. Dr. Sheth has disclosed no relevant financial relationships.

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

In large-vessel occlusion stroke, results of a randomized trial failed to show noninferiority of direct mechanical thrombectomy using the Solitaire device to the combination of intravenous (IV) thrombolysis plus mechanical thrombectomy.

In the prospective, multicenter trial, the rate of good functional outcome was 57% for patients who underwent direct thrombectomy and 65% among patients who received IV thrombolysis before undergoing thrombectomy. This result failed to demonstrate noninferiority of direct mechanical thrombectomy compared to combination therapy, the researchers conclude.

“Good outcome was high in both treatment arms, with the point estimate in favor of the bridging cohort,” said lead investigator Urs Fischer, MD, co-chair of the stroke center at Inselspital, Bern University Hospital, Switzerland, during his presentation. “Postinterventional reperfusion was very high in both treatment arms and higher in patients with bridging thrombolysis, compared to direct mechanical thrombectomy.”

The findings were presented at the 13th World Stroke Congress (WSC) 2021.
 

Two views of thrombolysis

The value of bridging thrombolysis for patients who undergo mechanical thrombectomy is a matter of debate. One argument is that, for patients with large-vessel occlusion, IV thrombolysis may improve reperfusion before and after thrombectomy and yield better clinical outcomes. The opposing argument is that bridging thrombolysis may increase the risk for distal emboli, delay mechanical thrombectomy, and increase the rate of hemorrhage.

The researchers conducted the SWIFT DIRECT trial to investigate this question. They enrolled patients with acute ischemic stroke due to occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery.

The trial was conducted at 48 sites in seven European countries and Canada. The investigators randomly assigned patients to receive IV alteplase (0.9 mg/kg) plus mechanical thrombectomy with the Solitaire device or to receive direct mechanical thrombectomy with the same device. Treatment was open label, but the assessment of endpoints was blinded.

Investigators assigned 423 patients to treatment, and 408 were included in the full analysis set. Of this group, 201 participants received direct mechanical thrombectomy, and 207 received IV thrombolysis plus thrombectomy. There were three crossovers in each treatment arm.

The primary outcome was functional independence, defined as a Modified Rankin Scale (mRS) score of 0-2, at 90 days. Secondary outcomes included mortality at 90 days, mRS shift, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, successful reperfusion, and symptomatic and asymptomatic intracranial hemorrhage (ICH).
 

Noninferiority not demonstrated

At baseline, patient characteristics were well balanced between the treatment groups. The median age of the patients was 72 years, and about 50% of participants were women. The median NIHSS score was 17 in both arms.

Approximately 57% of patients who underwent direct thrombectomy and 65% of those who received IV thrombolysis plus thrombectomy were functionally independent at 90 days, the primary outcome.

In addition, the researchers found no difference in mRS shift, mortality at 90 days, or change in NIHSS score at 24 hours. Postinterventional reperfusion was very high in both arms and was higher in patients who received IV tissue plasminogen activator, compared with those who received direct mechanical thrombectomy, said Dr. Fischer.

The rate of successful postinterventional reperfusion, however, was higher among patients who received thrombolysis than among those who underwent direct thrombectomy. The rate of symptomatic ICH was 1.5% in the direct thrombectomy group and 4.9% in the thrombolysis-plus-thrombectomy group.
 

New endpoints needed?

The investigators used noninferiority margins of 12%. “This question about the noninferiority margins, that’s a very tricky and difficult one in randomized clinical trials,” said Dr. Fischer. The investigators defined their margin using the 2015 HERMES data because no trials had yet compared direct mechanical thrombectomy and bridging thrombolysis at the time.

The researchers are performing a pooled analysis of all the trials that compared bridging thrombolysis with direct mechanical thrombectomy. “We are therefore looking at several margins, and I think this is the way we should look at these noninferiority margins,” said Dr. Fischer. “There’s not a clear-cut level which you can define.”

Enrollment in the trial was well balanced with respect to gender, which is not always the case in stroke studies, said Kevin Sheth, MD, professor of neurology and neurosurgery at Yale School of Medicine, New Haven, Conn., who commented on the study for this news organization.

The findings indicate that the likelihood of there being a difference between groups on this question is low, said Dr. Sheth. Both groups had large-vessel occlusion, both received thrombectomy, and both achieved reperfusion. But the higher rate of successful reperfusion in the bridging cohort was not reflected in any of the clinical endpoints that the investigators examined.

Observing a difference in this context will require very large trials or different endpoints that are more responsive to the intervention, said Dr. Sheth. “This is going to be a challenge for not just this but for any neuroprotection trial in the future,” he said.

The study was supported by Medtronic. Dr. Fischer has served as a consultant for Medtronic, Stryker, and CSL Behring. Dr. Sheth has disclosed no relevant financial relationships.

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

In large-vessel occlusion stroke, results of a randomized trial failed to show noninferiority of direct mechanical thrombectomy using the Solitaire device to the combination of intravenous (IV) thrombolysis plus mechanical thrombectomy.

In the prospective, multicenter trial, the rate of good functional outcome was 57% for patients who underwent direct thrombectomy and 65% among patients who received IV thrombolysis before undergoing thrombectomy. This result failed to demonstrate noninferiority of direct mechanical thrombectomy compared to combination therapy, the researchers conclude.

“Good outcome was high in both treatment arms, with the point estimate in favor of the bridging cohort,” said lead investigator Urs Fischer, MD, co-chair of the stroke center at Inselspital, Bern University Hospital, Switzerland, during his presentation. “Postinterventional reperfusion was very high in both treatment arms and higher in patients with bridging thrombolysis, compared to direct mechanical thrombectomy.”

The findings were presented at the 13th World Stroke Congress (WSC) 2021.
 

Two views of thrombolysis

The value of bridging thrombolysis for patients who undergo mechanical thrombectomy is a matter of debate. One argument is that, for patients with large-vessel occlusion, IV thrombolysis may improve reperfusion before and after thrombectomy and yield better clinical outcomes. The opposing argument is that bridging thrombolysis may increase the risk for distal emboli, delay mechanical thrombectomy, and increase the rate of hemorrhage.

The researchers conducted the SWIFT DIRECT trial to investigate this question. They enrolled patients with acute ischemic stroke due to occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery.

The trial was conducted at 48 sites in seven European countries and Canada. The investigators randomly assigned patients to receive IV alteplase (0.9 mg/kg) plus mechanical thrombectomy with the Solitaire device or to receive direct mechanical thrombectomy with the same device. Treatment was open label, but the assessment of endpoints was blinded.

Investigators assigned 423 patients to treatment, and 408 were included in the full analysis set. Of this group, 201 participants received direct mechanical thrombectomy, and 207 received IV thrombolysis plus thrombectomy. There were three crossovers in each treatment arm.

The primary outcome was functional independence, defined as a Modified Rankin Scale (mRS) score of 0-2, at 90 days. Secondary outcomes included mortality at 90 days, mRS shift, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, successful reperfusion, and symptomatic and asymptomatic intracranial hemorrhage (ICH).
 

Noninferiority not demonstrated

At baseline, patient characteristics were well balanced between the treatment groups. The median age of the patients was 72 years, and about 50% of participants were women. The median NIHSS score was 17 in both arms.

Approximately 57% of patients who underwent direct thrombectomy and 65% of those who received IV thrombolysis plus thrombectomy were functionally independent at 90 days, the primary outcome.

In addition, the researchers found no difference in mRS shift, mortality at 90 days, or change in NIHSS score at 24 hours. Postinterventional reperfusion was very high in both arms and was higher in patients who received IV tissue plasminogen activator, compared with those who received direct mechanical thrombectomy, said Dr. Fischer.

The rate of successful postinterventional reperfusion, however, was higher among patients who received thrombolysis than among those who underwent direct thrombectomy. The rate of symptomatic ICH was 1.5% in the direct thrombectomy group and 4.9% in the thrombolysis-plus-thrombectomy group.
 

New endpoints needed?

The investigators used noninferiority margins of 12%. “This question about the noninferiority margins, that’s a very tricky and difficult one in randomized clinical trials,” said Dr. Fischer. The investigators defined their margin using the 2015 HERMES data because no trials had yet compared direct mechanical thrombectomy and bridging thrombolysis at the time.

The researchers are performing a pooled analysis of all the trials that compared bridging thrombolysis with direct mechanical thrombectomy. “We are therefore looking at several margins, and I think this is the way we should look at these noninferiority margins,” said Dr. Fischer. “There’s not a clear-cut level which you can define.”

Enrollment in the trial was well balanced with respect to gender, which is not always the case in stroke studies, said Kevin Sheth, MD, professor of neurology and neurosurgery at Yale School of Medicine, New Haven, Conn., who commented on the study for this news organization.

The findings indicate that the likelihood of there being a difference between groups on this question is low, said Dr. Sheth. Both groups had large-vessel occlusion, both received thrombectomy, and both achieved reperfusion. But the higher rate of successful reperfusion in the bridging cohort was not reflected in any of the clinical endpoints that the investigators examined.

Observing a difference in this context will require very large trials or different endpoints that are more responsive to the intervention, said Dr. Sheth. “This is going to be a challenge for not just this but for any neuroprotection trial in the future,” he said.

The study was supported by Medtronic. Dr. Fischer has served as a consultant for Medtronic, Stryker, and CSL Behring. Dr. Sheth has disclosed no relevant financial relationships.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

COVID-19 has been difficult for parents trying to balance careers, home life, and keeping their loved ones safe. A new study indicates that, not only are physicians not immune to these stressors, but the long-term effects could be devastating for health care overall.

Juanmonino/Getty Images

In a study published Nov. 11, 2021, in JAMA Network Open , researchers found that stresses to work/life balance and family life caused by the pandemic have differed among men and women physicians. Women physicians have borne more of the burden, and the consequences could reach far beyond home.

Physicians and other health care workers have been at the front lines of the COVID-19 pandemic, and their work lives have been the focus of a lot of attention in the media and by researchers. Their family lives, not so much. But physicians have families, and the pandemic has upended almost everything about their lives, particularly where work life and home life intersect. School and day care closures, working from home, working extra hours, or working less – all of these changes have consequences on family life and the mental health of parents who are also physicians.

Findings from a Medscape survey published in early 2021 indicate that more female physicians than male physicians were either “conflicted” or “very conflicted” as parents because of work demands (42% vs. 23%) nearly 6 months into the pandemic.

In the current study, researchers from the University of Michigan, Harvard University, and the Medical University of South Carolina teamed up to investigate gender differences in how work/family factors affected the mental health of early-career physician parents in the United States during the first year of the COVID-19 pandemic. The results suggest that the pandemic has increased gender disparity and added disproportionately to the burden of female physicians.
 

Managing the household falls mostly on moms

Participants were physicians enrolled in the Intern Health Study, a longitudinal study that regularly surveys medical interns in the United States to assess stress and mood. When researchers compared survey results from before the onset of the pandemic (2018) with later results (2020), they found a striking gender difference in how the pandemic has changed family and work duties for physicians.

The authors of the study pointed out that previous research had found that female physicians take on a greater share of household and childcare duties than male physicians. The current study found that their share had increased with the pandemic. Physician moms are now 30 times more likely to be in charge of these tasks than physician dads.

In families in which both parents were physicians, none of the men said they took the primary role in managing the extra demands caused by the pandemic. In addition, women were twice as likely as men to work primarily from home and to work reduced hours.

The extra stress seems to be taking a toll on women physicians. In the 2020 survey, physician mothers had higher scores for anxiety and depression symptoms, compared with men. Notably, the 2018 survey did not show a significant difference in depression scores between men and women. Nor were there significant differences in depression and anxiety scores between women and men who were not parents or in reports of work/family conflict before and after the pandemic.

In general, the results indicate that the pandemic has only widened the gender gap between women and men physicians when it comes to managing family life and dealing with the stresses of maintaining a suitable work-life balance.
 

‘Long-term repercussions’ for gender equity in medicine

Although these are serious problems for women physicians and their families, the effects go beyond the home and beyond individuals. Even before the pandemic, women in medicine struggled for parity in career advancement and opportunities as well as in pay, and this new setback could make those challenges even greater.

“Even short-term adjustments can have serious long-term repercussions as they may lead to lower earnings and negatively impact opportunities for promotion, further exacerbating gender inequalities in compensation and advancement,” the study’s authors wrote.

The potential damage extends to the entire profession and the health care system itself. The profession is already struggling to retain young female physicians, and this situation is likely to make that problem worse and have long-term consequences. Citing data showing that female physicians spend more time with patients and that their patients may have better outcomes, the authors wrote that the consequences of losing more early-career female physicians “could be devastating to the U.S. health care system, particularly in the context of a global pandemic and an impending physician shortage.”

The sample size was small (276 U.S. physicians), and the study relied on self-reported data. The findings suggest that more research on this topic is needed, especially research that includes other demographic factors, such as sexual orientation and ethnicity. The authors recommend that institutional and public policymakers take into account the effects of the pandemic on physician mothers to ensure that recent gains in gender equity for women physicians do not fall victim to COVID-19.

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

The STEP 5 clinical trial extends favorable weight loss from 1 year out to 2 years for the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy, Novo Nordisk), given as a once-weekly 2.4-mg subcutaneous injection, and some food cravings were improved in a subgroup analysis.

In another study, STEP 8, weight loss was greater at 68 weeks with semaglutide subcutaneous injection than with a 3-mg daily subcutaneous injection of another GLP-1 agonist, liraglutide (Saxenda, Novo Nordisk), approved earlier for weight loss.

Researchers presented these promising outcomes, with no new safety signals, at ObesityWeek® 2021.

However, there is more to learn about the drug class, researchers agree. Follow-up is still relatively short for a chronic disease and many patients have gastrointestinal side effects with semaglutide, one expert cautions.

The key findings were:

In STEP 5, combined with lifestyle intervention (a reduced-calorie meal plan and advice about physical activity), weekly injection of 2.4 mg semaglutide led to:

• 15.2% weight loss, compared with 2.6% weight loss with placebo at 2 years (P < .0001);
• 77% of patients losing at least 5% of their weight, compared with 34% of patients in the placebo group at 2 years (P < .0001);
• Significantly greater improvement in overall control of cravings, and craving for savory foods, in a subset of patients, versus placebo, but questionnaire scores for positive mood and craving for sweet foods were similar in both groups.
• In STEP 8, mean body weight at 68 weeks was 15.8% lower with 2.4 mg/week subcutaneous semaglutide plus lifestyle changes versus 6.4% lower with 3.0 mg/day subcutaneous liraglutide plus lifestyle changes (P < .001).

Can treat to a target weight-loss range

The undiminished weight loss efficacy in the 2-year data for STEP 5 “portends well,” said W. Timothy Garvey, MD, following his presentation of the results.

Weight loss plus reduced cravings

In another presentation, Sean Wharton, MD, PharmD, said, “In adults with overweight or obesity, substantial weight loss with semaglutide 2.4 mg was accompanied by short- and long-term improvements in control of eating.”

Clinically meaningful weight loss

When presenting the STEP 8 findings, Domenica M. Rubino, MD, said: “Participants were significantly more likely to achieve clinically meaningful weight loss thresholds with semaglutide 2.4 mg versus liraglutide 3.0 mg, accompanied by greater improvements in cardiometabolic risk factors.”

For example, patients can have better mobility, which is important for quality of life, Dr. Rubino, director of the Washington Center for Weight Management and Research, Arlington, Virginia, noted. 

A smaller percentage of patients respond to liraglutide, she added. Clinicians need to individualize treatment.

When asked, “How do you choose which medical therapy?” Dr. Rubino responded: “We sit and talk.” Finding the medical therapy that fits the patient depends on things such as the patient’s insurance coverage and ability to tolerate side effects such as dehydration, diarrhea, and nausea.   

When asked, “How do you switch from liraglutide to semaglutide?” she noted that there are no current guidelines for this. “You have to be careful. Start on the lowest dose of Wegovy. Be cautious, conservative.”  
 

Still early days, caveats remain

“The STEP trials as a group appear to be making the case that obesity may now be considered a medically manageable disease, based on the experience with semaglutide,” Julie R. Ingelfinger, MD, who was not involved with the research, commented in an email.

STEP 5 weight loss efficacy and safety at 2 years

Garvey reported that STEP 5 was a phase 3b trial that randomized 304 adults in the United States, Canada, Hungary, Italy, and Spain, who were 18 years and older, with a body mass index (BMI) ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) or a BMI ≥30 kg/m², without type 2 diabetes, to receive semaglutide or placebo plus lifestyle intervention.

Most participants were women (78%) and White (93%). On average, they were 47 years old, weighed 106 kg (223.7 pounds), had a BMI of 38.5 kg/m², a waist circumference of 115.7 cm (45.6 inches), and an A1c of 5.7%.

A total of 87% of patients in the semaglutide group and 73% of patients in the placebo group completed the trial.

At 104 weeks, participants were more likely to lose ≥10%, ≥15%, and ≥20% of body weight with semaglutide versus placebo (61.8% vs. 13.3%, 52.1% vs. 7.0%, and 36.1% vs. 2.3%, respectively; P < .0001 for all).

Patients in the semaglutide group had greater health improvements in cardiovascular risk factors (waist circumference, systolic and diastolic blood pressure, and C-reactive protein) and metabolic risk factors (A1c, fasting plasma glucose, fasting serum insulin, and triglycerides) than those in the placebo group (P < .05 for all).

Safety and tolerability were consistent with adverse events seen with this drug class, with no new safety signals.
 

Control of eating questionnaire findings at 2 years in STEP 5

Dr. Wharton and colleagues assessed changes in responses to the Control of Eating questionnaire at baseline and at 20, 52, and 104 weeks in patients from the U.S. and Canada in the STEP 5 trial (88 patients in the semaglutide group and 86 patients in the placebo group).

The questionnaire consisted of 19 questions grouped into four categories: control of food cravings, craving for savory foods (salty and spicy, dairy, or starchy foods), craving for sweet foods (chocolate, sweet foods, or fruit/fruit juice), and positive mood.

At week 104, patients in the semaglutide group had significantly greater improvements in scores for craving for salty and spicy, dairy, and starchy foods, and resisting cravings.
 

Semaglutide versus liraglutide, 68-week efficacy and safety in STEP 8

STEP 8 randomized 338 U.S. adults without diabetes and a BMI of ≥27 kg/m² plus one or more weight-related comorbidities or a BMI of ≥30 kg/m² 3:1 to semaglutide 2.4 mg once weekly (n = 126) or matching placebo, or 3:1 liraglutide 3.0 mg once daily (n = 127) or matching placebo, plus lifestyle intervention.

Most participants were women (78%) and were a mean age of 49, had a mean body weight of 104.5 kg, and had a mean BMI of 37.5 kg/m².

In STEP 8, more participants achieved ≥10%, ≥15%, and ≥20% weight loss with semaglutide than with liraglutide (70.9% vs. 25.6%, 55.6% vs. 12.0%, and 38.5% vs. 6.0%, respectively; P < .001 for all odds ratios).

Semaglutide improved waist circumference, A1c, and C-reactive protein versus liraglutide (unadjusted P < .001 for all).

Gastrointestinal adverse events were reported by 84% and 83% of participants receiving semaglutide and liraglutide, respectively. Most events were mild/moderate and transient, with prevalence declining over time.

Fewer participants stopped treatment due to adverse events with semaglutide than liraglutide (3.2% vs. 12.6%).

Dr. Garvey has reported serving as a site principal investigator for multicentered clinical trials sponsored by his university and funded by Eli Lilly, Novo Nordisk, and Pfizer. Dr. Wharton has reported financial ties to Novo Nordisk, Bausch Health Canada, Eli Lily, and Boehringer Ingelheim Canada. Dr. Rubino has reported ties to Boehringer Ingelheim and AstraZeneca. Dr. Ingelfinger has reported no relevant financial relationships.

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

The STEP 5 clinical trial extends favorable weight loss from 1 year out to 2 years for the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy, Novo Nordisk), given as a once-weekly 2.4-mg subcutaneous injection, and some food cravings were improved in a subgroup analysis.

In another study, STEP 8, weight loss was greater at 68 weeks with semaglutide subcutaneous injection than with a 3-mg daily subcutaneous injection of another GLP-1 agonist, liraglutide (Saxenda, Novo Nordisk), approved earlier for weight loss.

Researchers presented these promising outcomes, with no new safety signals, at ObesityWeek® 2021.

However, there is more to learn about the drug class, researchers agree. Follow-up is still relatively short for a chronic disease and many patients have gastrointestinal side effects with semaglutide, one expert cautions.

The key findings were:

In STEP 5, combined with lifestyle intervention (a reduced-calorie meal plan and advice about physical activity), weekly injection of 2.4 mg semaglutide led to:

• 15.2% weight loss, compared with 2.6% weight loss with placebo at 2 years (P < .0001);
• 77% of patients losing at least 5% of their weight, compared with 34% of patients in the placebo group at 2 years (P < .0001);
• Significantly greater improvement in overall control of cravings, and craving for savory foods, in a subset of patients, versus placebo, but questionnaire scores for positive mood and craving for sweet foods were similar in both groups.
• In STEP 8, mean body weight at 68 weeks was 15.8% lower with 2.4 mg/week subcutaneous semaglutide plus lifestyle changes versus 6.4% lower with 3.0 mg/day subcutaneous liraglutide plus lifestyle changes (P < .001).

Can treat to a target weight-loss range

The undiminished weight loss efficacy in the 2-year data for STEP 5 “portends well,” said W. Timothy Garvey, MD, following his presentation of the results.

Weight loss plus reduced cravings

In another presentation, Sean Wharton, MD, PharmD, said, “In adults with overweight or obesity, substantial weight loss with semaglutide 2.4 mg was accompanied by short- and long-term improvements in control of eating.”

Clinically meaningful weight loss

When presenting the STEP 8 findings, Domenica M. Rubino, MD, said: “Participants were significantly more likely to achieve clinically meaningful weight loss thresholds with semaglutide 2.4 mg versus liraglutide 3.0 mg, accompanied by greater improvements in cardiometabolic risk factors.”

For example, patients can have better mobility, which is important for quality of life, Dr. Rubino, director of the Washington Center for Weight Management and Research, Arlington, Virginia, noted. 

A smaller percentage of patients respond to liraglutide, she added. Clinicians need to individualize treatment.

When asked, “How do you choose which medical therapy?” Dr. Rubino responded: “We sit and talk.” Finding the medical therapy that fits the patient depends on things such as the patient’s insurance coverage and ability to tolerate side effects such as dehydration, diarrhea, and nausea.   

When asked, “How do you switch from liraglutide to semaglutide?” she noted that there are no current guidelines for this. “You have to be careful. Start on the lowest dose of Wegovy. Be cautious, conservative.”  
 

Still early days, caveats remain

“The STEP trials as a group appear to be making the case that obesity may now be considered a medically manageable disease, based on the experience with semaglutide,” Julie R. Ingelfinger, MD, who was not involved with the research, commented in an email.

STEP 5 weight loss efficacy and safety at 2 years

Garvey reported that STEP 5 was a phase 3b trial that randomized 304 adults in the United States, Canada, Hungary, Italy, and Spain, who were 18 years and older, with a body mass index (BMI) ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) or a BMI ≥30 kg/m², without type 2 diabetes, to receive semaglutide or placebo plus lifestyle intervention.

Most participants were women (78%) and White (93%). On average, they were 47 years old, weighed 106 kg (223.7 pounds), had a BMI of 38.5 kg/m², a waist circumference of 115.7 cm (45.6 inches), and an A1c of 5.7%.

A total of 87% of patients in the semaglutide group and 73% of patients in the placebo group completed the trial.

At 104 weeks, participants were more likely to lose ≥10%, ≥15%, and ≥20% of body weight with semaglutide versus placebo (61.8% vs. 13.3%, 52.1% vs. 7.0%, and 36.1% vs. 2.3%, respectively; P < .0001 for all).

Patients in the semaglutide group had greater health improvements in cardiovascular risk factors (waist circumference, systolic and diastolic blood pressure, and C-reactive protein) and metabolic risk factors (A1c, fasting plasma glucose, fasting serum insulin, and triglycerides) than those in the placebo group (P < .05 for all).

Safety and tolerability were consistent with adverse events seen with this drug class, with no new safety signals.
 

Control of eating questionnaire findings at 2 years in STEP 5

Dr. Wharton and colleagues assessed changes in responses to the Control of Eating questionnaire at baseline and at 20, 52, and 104 weeks in patients from the U.S. and Canada in the STEP 5 trial (88 patients in the semaglutide group and 86 patients in the placebo group).

The questionnaire consisted of 19 questions grouped into four categories: control of food cravings, craving for savory foods (salty and spicy, dairy, or starchy foods), craving for sweet foods (chocolate, sweet foods, or fruit/fruit juice), and positive mood.

At week 104, patients in the semaglutide group had significantly greater improvements in scores for craving for salty and spicy, dairy, and starchy foods, and resisting cravings.
 

Semaglutide versus liraglutide, 68-week efficacy and safety in STEP 8

STEP 8 randomized 338 U.S. adults without diabetes and a BMI of ≥27 kg/m² plus one or more weight-related comorbidities or a BMI of ≥30 kg/m² 3:1 to semaglutide 2.4 mg once weekly (n = 126) or matching placebo, or 3:1 liraglutide 3.0 mg once daily (n = 127) or matching placebo, plus lifestyle intervention.

Most participants were women (78%) and were a mean age of 49, had a mean body weight of 104.5 kg, and had a mean BMI of 37.5 kg/m².

In STEP 8, more participants achieved ≥10%, ≥15%, and ≥20% weight loss with semaglutide than with liraglutide (70.9% vs. 25.6%, 55.6% vs. 12.0%, and 38.5% vs. 6.0%, respectively; P < .001 for all odds ratios).

Semaglutide improved waist circumference, A1c, and C-reactive protein versus liraglutide (unadjusted P < .001 for all).

Gastrointestinal adverse events were reported by 84% and 83% of participants receiving semaglutide and liraglutide, respectively. Most events were mild/moderate and transient, with prevalence declining over time.

Fewer participants stopped treatment due to adverse events with semaglutide than liraglutide (3.2% vs. 12.6%).

Dr. Garvey has reported serving as a site principal investigator for multicentered clinical trials sponsored by his university and funded by Eli Lilly, Novo Nordisk, and Pfizer. Dr. Wharton has reported financial ties to Novo Nordisk, Bausch Health Canada, Eli Lily, and Boehringer Ingelheim Canada. Dr. Rubino has reported ties to Boehringer Ingelheim and AstraZeneca. Dr. Ingelfinger has reported no relevant financial relationships.

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

The STEP 5 clinical trial extends favorable weight loss from 1 year out to 2 years for the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy, Novo Nordisk), given as a once-weekly 2.4-mg subcutaneous injection, and some food cravings were improved in a subgroup analysis.

In another study, STEP 8, weight loss was greater at 68 weeks with semaglutide subcutaneous injection than with a 3-mg daily subcutaneous injection of another GLP-1 agonist, liraglutide (Saxenda, Novo Nordisk), approved earlier for weight loss.

Researchers presented these promising outcomes, with no new safety signals, at ObesityWeek® 2021.

However, there is more to learn about the drug class, researchers agree. Follow-up is still relatively short for a chronic disease and many patients have gastrointestinal side effects with semaglutide, one expert cautions.

The key findings were:

In STEP 5, combined with lifestyle intervention (a reduced-calorie meal plan and advice about physical activity), weekly injection of 2.4 mg semaglutide led to:

• 15.2% weight loss, compared with 2.6% weight loss with placebo at 2 years (P < .0001);
• 77% of patients losing at least 5% of their weight, compared with 34% of patients in the placebo group at 2 years (P < .0001);
• Significantly greater improvement in overall control of cravings, and craving for savory foods, in a subset of patients, versus placebo, but questionnaire scores for positive mood and craving for sweet foods were similar in both groups.
• In STEP 8, mean body weight at 68 weeks was 15.8% lower with 2.4 mg/week subcutaneous semaglutide plus lifestyle changes versus 6.4% lower with 3.0 mg/day subcutaneous liraglutide plus lifestyle changes (P < .001).

Can treat to a target weight-loss range

The undiminished weight loss efficacy in the 2-year data for STEP 5 “portends well,” said W. Timothy Garvey, MD, following his presentation of the results.

Weight loss plus reduced cravings

In another presentation, Sean Wharton, MD, PharmD, said, “In adults with overweight or obesity, substantial weight loss with semaglutide 2.4 mg was accompanied by short- and long-term improvements in control of eating.”

Clinically meaningful weight loss

When presenting the STEP 8 findings, Domenica M. Rubino, MD, said: “Participants were significantly more likely to achieve clinically meaningful weight loss thresholds with semaglutide 2.4 mg versus liraglutide 3.0 mg, accompanied by greater improvements in cardiometabolic risk factors.”

For example, patients can have better mobility, which is important for quality of life, Dr. Rubino, director of the Washington Center for Weight Management and Research, Arlington, Virginia, noted. 

A smaller percentage of patients respond to liraglutide, she added. Clinicians need to individualize treatment.

When asked, “How do you choose which medical therapy?” Dr. Rubino responded: “We sit and talk.” Finding the medical therapy that fits the patient depends on things such as the patient’s insurance coverage and ability to tolerate side effects such as dehydration, diarrhea, and nausea.   

When asked, “How do you switch from liraglutide to semaglutide?” she noted that there are no current guidelines for this. “You have to be careful. Start on the lowest dose of Wegovy. Be cautious, conservative.”  
 

Still early days, caveats remain

“The STEP trials as a group appear to be making the case that obesity may now be considered a medically manageable disease, based on the experience with semaglutide,” Julie R. Ingelfinger, MD, who was not involved with the research, commented in an email.

STEP 5 weight loss efficacy and safety at 2 years

Garvey reported that STEP 5 was a phase 3b trial that randomized 304 adults in the United States, Canada, Hungary, Italy, and Spain, who were 18 years and older, with a body mass index (BMI) ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) or a BMI ≥30 kg/m², without type 2 diabetes, to receive semaglutide or placebo plus lifestyle intervention.

Most participants were women (78%) and White (93%). On average, they were 47 years old, weighed 106 kg (223.7 pounds), had a BMI of 38.5 kg/m², a waist circumference of 115.7 cm (45.6 inches), and an A1c of 5.7%.

A total of 87% of patients in the semaglutide group and 73% of patients in the placebo group completed the trial.

At 104 weeks, participants were more likely to lose ≥10%, ≥15%, and ≥20% of body weight with semaglutide versus placebo (61.8% vs. 13.3%, 52.1% vs. 7.0%, and 36.1% vs. 2.3%, respectively; P < .0001 for all).

Patients in the semaglutide group had greater health improvements in cardiovascular risk factors (waist circumference, systolic and diastolic blood pressure, and C-reactive protein) and metabolic risk factors (A1c, fasting plasma glucose, fasting serum insulin, and triglycerides) than those in the placebo group (P < .05 for all).

Safety and tolerability were consistent with adverse events seen with this drug class, with no new safety signals.
 

Control of eating questionnaire findings at 2 years in STEP 5

Dr. Wharton and colleagues assessed changes in responses to the Control of Eating questionnaire at baseline and at 20, 52, and 104 weeks in patients from the U.S. and Canada in the STEP 5 trial (88 patients in the semaglutide group and 86 patients in the placebo group).

The questionnaire consisted of 19 questions grouped into four categories: control of food cravings, craving for savory foods (salty and spicy, dairy, or starchy foods), craving for sweet foods (chocolate, sweet foods, or fruit/fruit juice), and positive mood.

At week 104, patients in the semaglutide group had significantly greater improvements in scores for craving for salty and spicy, dairy, and starchy foods, and resisting cravings.
 

Semaglutide versus liraglutide, 68-week efficacy and safety in STEP 8

STEP 8 randomized 338 U.S. adults without diabetes and a BMI of ≥27 kg/m² plus one or more weight-related comorbidities or a BMI of ≥30 kg/m² 3:1 to semaglutide 2.4 mg once weekly (n = 126) or matching placebo, or 3:1 liraglutide 3.0 mg once daily (n = 127) or matching placebo, plus lifestyle intervention.

Most participants were women (78%) and were a mean age of 49, had a mean body weight of 104.5 kg, and had a mean BMI of 37.5 kg/m².

In STEP 8, more participants achieved ≥10%, ≥15%, and ≥20% weight loss with semaglutide than with liraglutide (70.9% vs. 25.6%, 55.6% vs. 12.0%, and 38.5% vs. 6.0%, respectively; P < .001 for all odds ratios).

Semaglutide improved waist circumference, A1c, and C-reactive protein versus liraglutide (unadjusted P < .001 for all).

Gastrointestinal adverse events were reported by 84% and 83% of participants receiving semaglutide and liraglutide, respectively. Most events were mild/moderate and transient, with prevalence declining over time.

Fewer participants stopped treatment due to adverse events with semaglutide than liraglutide (3.2% vs. 12.6%).

Dr. Garvey has reported serving as a site principal investigator for multicentered clinical trials sponsored by his university and funded by Eli Lilly, Novo Nordisk, and Pfizer. Dr. Wharton has reported financial ties to Novo Nordisk, Bausch Health Canada, Eli Lily, and Boehringer Ingelheim Canada. Dr. Rubino has reported ties to Boehringer Ingelheim and AstraZeneca. Dr. Ingelfinger has reported no relevant financial relationships.

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

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

On the basis of outcomes, there was no clear winner from a trial that directly compared two modern devices used in patients undergoing percutaneous left atrial appendage (LAA) closure.

But the devices were not interchangeable for rates of complications or leaks, according to results of the open-label SWISS APERO trial, which compared the Amplatzer Amulet to the Watchman FLX device at eight participating centers in Europe.

At 45 days, the overall rates of leaks and the clinical outcomes in the two randomized groups were not significantly different, but there were differences in secondary endpoints, such as rates of peridevice leak (PDL), which were lower in the Amulet device group, and procedural complications, which were higher, Roberto Galea, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando.

LAA closure devices were developed as an alternative to oral anticoagulation in patients with nonvalvular atrial fibrillation. Although a similar comparison of LAA closure devices, called Amulet IDE, was recently published, that trial compared Amulet to Watchman 2.5, an earlier generation device.

Started later, SWISS APERO was also a planned comparison of Amulet and the Watchman 2.5, but the comparison switched to the Watchman FLX, when it was released in March of 2019.
 

First randomized comparison with Watchman FLX

“This is the first multicenter randomized controlled trial to include the Watchman FLX,” said Dr. Galea, a clinical investigator in the department of cardiology, Bern (Switzerland) University Hospital. He noted that Watchman FLX included some adjustments in design with the potential to reduce leak rates.

After preprocedural transesophageal echocardiography confirmed that patients had suitable anatomy to receive either device, the 221 patients who qualified for SWISS APERO were randomized. The primary endpoint was a composite of a justified crossover to a device other than the one to which they were assigned or residual patency detected by coronary computed tomography angiography (CCTA) at 45 days.

The primary endpoint was reached by 67.6% of patients randomized to the Amulet device and 70% of those randomized to Watchman Flex, a statistically nonsignificant difference (P = .71).

Because only one patient in the Amulet group and none in the Watchman group had a justified crossover to a nonrandomized device, most of the differences in the 45-day CCTA involved patency, defined as LAA density of at least 100 Hounsfield units. While the proportion of patients with leaks was similar, the types of leaks, which were stratified by underlying leak mechanism into PDL, mixed leaks (including incomplete side sealing), intradevice leaks, and leaks of unclear origin, were different.
 

Peridevice leaks twofold greater with Watchman

Those randomized to the Watchman device were more than twice as likely to have PDL (27.5% vs. 13.7%; P = .02), although no visible leak exceeded 5 mm in size. They were also more likely to have mixed leaks (14% vs. 3.8%; P = .01) and patency with no visible leak (21.0% vs. 9.5%; P = .02). There were also more device-related thrombi in the Watchman group even though the difference did not reach statistical significance (9.9% vs. 3.7%; P = .08).

Intradevice leaks (44.8% vs. 23.0%; P = .001) were the only type of patency significantly more common among patients randomized to Amulet, but the difference was relatively large. In addition, procedural complications of any type (32.4% vs. 19.1%; P = .023) were higher in the Amulet group. Most of these involved non–clinically relevant pericardial effusions, Dr. Galea said at the meeting, sponsored by the Cardiovascular Research Foundation.

The proportion of patients with adverse outcomes by 45 days was similar, but the types of complications differed. Of the six deaths, two occurred in the Amulet group as a result of periprocedural complications (one stemming from an air embolism and the other from a series of events following pericardial effusion). Three of the four deaths in the Watchman group were due to fatal bleeding. The fourth was a sudden death that occurred 30 days after the procedure.
 

Amulet IDE trial generates similar data

The much larger Amulet IDE trial, which compared Amulet to the Watchman 2.5 device, produced generally similar results. Again, the proportion of patients reaching the composite primary endpoints was similar.

The primary safety endpoint, which included death and major bleeding within 12 months of randomization, occurred in 14.5% and 14.7% of the Amulet and Watchman patients, respectively (P < .001 for noninferiority). The primary efficacy endpoint, which included stroke or systemic embolism within 18 months of randomization, occurred in 2.8% of patients in both groups.

As in SWISS APERO, the 1,878-patient Amulet IDE trial showed that the devices are similarly effective and safe but not necessarily interchangeable. Ultimately, the rate of LAA occlusion was higher for Amulet than the older generation Watchman (98.9% vs. 96.8%; P = .003) but procedural complication occurred more frequently among those randomized to the Amulet device (4.5% vs. 2.5%).

“The closure mechanisms are not the same, which might explain why we see differences in some secondary outcomes even when they perform similarly on the primary outcomes,” said Dhanunjaya R. Lakkireddy, MD, executive medical director, Kansas City (Kansas) Heart Rhythm Institute.

The lead investigator of the Amulet IDE trial, Dr. Lakkireddy was referring to both the AMULET IDE and the SWISS APERO study when he said that the currently available data do not allow one device to be considered superior to the other. He did suggest that differences between devices might still be considered meaningful in specific clinical situations or to specific clinicians.

Without studies to show objective differences, Dr. Lakkireddy suggested that training and experience is probably the most important variable in achieving treatment goals. “Operator comfort is certainly important,” he said.

Dr. Galea reports no significant financial relationships. The investigator-initiated study received funding from Abbott, the manufacturer of the Amulet device. Dr. Lakkireddy has financial relationships with Abbott, AltaThera, Medtronic, Biotronik, and Boston Scientific, which makes the Watchman device.

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

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

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

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

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR – with a prosthesis designed for the mitral position and previously tested only transapically – has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Dr. Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Dr. Zahr, who is also lead author on the study’s Nov. 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Dr. Zahr’s formal presentation. Dr. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at New York-Presbyterian/Columbia University Irving Medical Center, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Dr. Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, but “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Dr. Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Dr. Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For trans-septal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minn.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

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