Stroke

Perhaps short, asymptomatic bouts of atrial fibrillation (AFib) that show up on long-term, continuous monitoring aren’t worth hunting for just so oral anticoagulation (OAC) can be started, even in elderly people with other stroke risk factors.

That’s a potential message from a randomized trial that tested an AFib screening strategy relying on an implantable loop recorder (ILR) in older adults without AFib but with other stroke risk factors who were invited to participate. OAC was recommended to any participant found with even a short bout of the arrhythmia (that is, any lasting 6 minutes or longer).

More than three times as many in the monitoring group compared to a standard-care cohort were found to have AFib, and nearly all were put on OAC. In fact, monitored participants were almost three times as likely to be put on OAC (P < .0001) compared with controls.

But it didn’t make any apparent difference to outcomes. The risk for stroke or systemic embolism did not significantly differ between the two groups over more than 5 years in the trial of about 6,000 participants, called LOOP.

“This result was seen despite a high proportion of atrial fibrillation detection, and a high acceptance of anticoagulation therapy, and might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation,” contend the authors of the LOOP report, simultaneously published in The Lancet and presented Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021.

“The rates of bleeding were modest, despite the low threshold for anticoagulation,” and was not significantly different between the two groups, Jesper H. Svendsen, MD, DMSc, Copenhagen University Hospital, Denmark, said at a media briefing before his presentation of the trial at the congress. He is lead author on the Lancet report.

At least 6 minutes of AFib was identified in more than 30% of the ILR-monitored patients, and about 90% of those were started on OAC, Dr. Svendsen observed.

But one take-home message from LOOP, he said in an interview, is that “short-lasting episodes” of AFib do not necessarily pose an untoward risk for stroke compared with AFib revealed by intermittent monitoring, which “primarily identifies longer-lasting atrial fibrillation episodes. So short-lasting episodes are probably not as serious as long-lasting.”

The LOOP trial “teaches us that perhaps short-lasting asymptomatic episodes may not benefit from being screened or found,” said Stefan James, MD, PhD, Uppsala University, Sweden. However, that may not be the case when the monitored individual is symptomatic or has longer-lasting AFib episodes, he said in an interview. “But certainly, this study teaches us that we need to understand much better the relationship between short episodes versus symptoms versus medical outcomes.”

In LOOP, 6,004 people aged 70-90 years without AFib but with at least one other stroke risk factor, which could include hypertension, diabetes, a history of stroke, or heart failure, were implanted with an ILR, the Reveal LINQ (Medtronic).

They were randomly assigned at four centers in Denmark to a monitoring group or a usual care group in a 1:3 ratio. Overwhelmingly, most had hypertension. Almost half the population were women.

OAC was recommended for all persons in the monitoring group who showed an episode of AFib lasting at least 6 minutes.

Atrial fibrillation was diagnosed in 31.8% of the 1,501 participants in the monitored group and 12.2% of the 4,503 assigned to usual care, for a hazard ratio (HR) of 3.17 (95% confidence interval, 2.81-3.59; P < .0001).

OAC was started in 29.7% of monitored participants and 13.1% of the control cohort, for an HR of 2.72 (95% CI, 2.41-3.08; P < .0001).

There were 315 strokes and three systemic arterial embolisms observed in the entire trial, for primary endpoint rates of 4.5% in the ILR monitoring group and 5.6% in the control group (HR, 0.80; 95% CI, 0.61-1.05; P = .11). Adding transient ischemic attack (TIA) or cardiovascular death to the endpoint did not make for a significant difference. The rates of major bleeding were 4.3% and 3.5%, respectively (P = .11).

“In general, the findings were consistent across subgroups,” including by age, sex, diabetes and heart failure status, stroke history, antiplatelet therapy, renal function, and even CHA2DS2–VASc score, Dr. Svendsen noted.

But, he said, participants in the highest tertile for baseline systolic blood pressure (BP), at least 157 mm Hg, “seemed to benefit from being screened,” with a 49% reduction in risk for the primary endpoint (P = .0066). The interaction between systolic BP and outcome was significant (P = .007).

Only 9.3% of participants in LOOP did not have a baseline diagnosis of hypertension and so had to have another risk factor to enroll, the published report notes. However, the significant interaction with systolic BP “suggests that patients with dysregulated hypertension could benefit from this type of screening and concomitant anticoagulation.”

“There is a tight association between our primary endpoint and hypertension,” Dr. Svendsen said in an interview. “But I think it’s very important to say that this subgroup analysis is only hypothesis-generating.”

An editorial accompanying the LOOP publication suggests, in line with Dr. Svendsen’s proposal, that “shorter atrial fibrillation episodes found by long-term ILRs might not have the same stroke risk as atrial fibrillation detected through single-timepoint or less intense monitoring.”

If much of the paroxysmal AFib observed in LOOP and other studies with similar monitoring methods “is not the actual cause of stroke and is instead predominantly a risk marker, further research is warranted to establish whether a different screening focus and treatment paradigm are required to prevent stroke and other vascular brain injury related to atrial fibrillation,” wrote editorialists Ben Freedman, MBBS, PhD, and Nicole Lowres, BPhty, PhD, University of Sydney, Australia.

LOOP was partially supported by Medtronic. Dr. Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. Disclosures for the other authors are in the report. Dr. Freedman reports grants to the Heart Research Institute, speakers fees and nonfinancial support from the Bristol-Myers Squibb–Pfizer Alliance, speakers fees and nonfinancial support from Daiichi Sankyo, nonfinancial support from AliveCor, and speakers fees and nonfinancial support from Omron unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation. Dr. Lowres reports grants to the Heart Research Institute from the Bristol-Myers Squibb–Pfizer Alliance unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation.

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

Perhaps short, asymptomatic bouts of atrial fibrillation (AFib) that show up on long-term, continuous monitoring aren’t worth hunting for just so oral anticoagulation (OAC) can be started, even in elderly people with other stroke risk factors.

That’s a potential message from a randomized trial that tested an AFib screening strategy relying on an implantable loop recorder (ILR) in older adults without AFib but with other stroke risk factors who were invited to participate. OAC was recommended to any participant found with even a short bout of the arrhythmia (that is, any lasting 6 minutes or longer).

More than three times as many in the monitoring group compared to a standard-care cohort were found to have AFib, and nearly all were put on OAC. In fact, monitored participants were almost three times as likely to be put on OAC (P < .0001) compared with controls.

But it didn’t make any apparent difference to outcomes. The risk for stroke or systemic embolism did not significantly differ between the two groups over more than 5 years in the trial of about 6,000 participants, called LOOP.

“This result was seen despite a high proportion of atrial fibrillation detection, and a high acceptance of anticoagulation therapy, and might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation,” contend the authors of the LOOP report, simultaneously published in The Lancet and presented Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021.

“The rates of bleeding were modest, despite the low threshold for anticoagulation,” and was not significantly different between the two groups, Jesper H. Svendsen, MD, DMSc, Copenhagen University Hospital, Denmark, said at a media briefing before his presentation of the trial at the congress. He is lead author on the Lancet report.

At least 6 minutes of AFib was identified in more than 30% of the ILR-monitored patients, and about 90% of those were started on OAC, Dr. Svendsen observed.

But one take-home message from LOOP, he said in an interview, is that “short-lasting episodes” of AFib do not necessarily pose an untoward risk for stroke compared with AFib revealed by intermittent monitoring, which “primarily identifies longer-lasting atrial fibrillation episodes. So short-lasting episodes are probably not as serious as long-lasting.”

The LOOP trial “teaches us that perhaps short-lasting asymptomatic episodes may not benefit from being screened or found,” said Stefan James, MD, PhD, Uppsala University, Sweden. However, that may not be the case when the monitored individual is symptomatic or has longer-lasting AFib episodes, he said in an interview. “But certainly, this study teaches us that we need to understand much better the relationship between short episodes versus symptoms versus medical outcomes.”

In LOOP, 6,004 people aged 70-90 years without AFib but with at least one other stroke risk factor, which could include hypertension, diabetes, a history of stroke, or heart failure, were implanted with an ILR, the Reveal LINQ (Medtronic).

They were randomly assigned at four centers in Denmark to a monitoring group or a usual care group in a 1:3 ratio. Overwhelmingly, most had hypertension. Almost half the population were women.

OAC was recommended for all persons in the monitoring group who showed an episode of AFib lasting at least 6 minutes.

Atrial fibrillation was diagnosed in 31.8% of the 1,501 participants in the monitored group and 12.2% of the 4,503 assigned to usual care, for a hazard ratio (HR) of 3.17 (95% confidence interval, 2.81-3.59; P < .0001).

OAC was started in 29.7% of monitored participants and 13.1% of the control cohort, for an HR of 2.72 (95% CI, 2.41-3.08; P < .0001).

There were 315 strokes and three systemic arterial embolisms observed in the entire trial, for primary endpoint rates of 4.5% in the ILR monitoring group and 5.6% in the control group (HR, 0.80; 95% CI, 0.61-1.05; P = .11). Adding transient ischemic attack (TIA) or cardiovascular death to the endpoint did not make for a significant difference. The rates of major bleeding were 4.3% and 3.5%, respectively (P = .11).

“In general, the findings were consistent across subgroups,” including by age, sex, diabetes and heart failure status, stroke history, antiplatelet therapy, renal function, and even CHA2DS2–VASc score, Dr. Svendsen noted.

But, he said, participants in the highest tertile for baseline systolic blood pressure (BP), at least 157 mm Hg, “seemed to benefit from being screened,” with a 49% reduction in risk for the primary endpoint (P = .0066). The interaction between systolic BP and outcome was significant (P = .007).

Only 9.3% of participants in LOOP did not have a baseline diagnosis of hypertension and so had to have another risk factor to enroll, the published report notes. However, the significant interaction with systolic BP “suggests that patients with dysregulated hypertension could benefit from this type of screening and concomitant anticoagulation.”

“There is a tight association between our primary endpoint and hypertension,” Dr. Svendsen said in an interview. “But I think it’s very important to say that this subgroup analysis is only hypothesis-generating.”

An editorial accompanying the LOOP publication suggests, in line with Dr. Svendsen’s proposal, that “shorter atrial fibrillation episodes found by long-term ILRs might not have the same stroke risk as atrial fibrillation detected through single-timepoint or less intense monitoring.”

If much of the paroxysmal AFib observed in LOOP and other studies with similar monitoring methods “is not the actual cause of stroke and is instead predominantly a risk marker, further research is warranted to establish whether a different screening focus and treatment paradigm are required to prevent stroke and other vascular brain injury related to atrial fibrillation,” wrote editorialists Ben Freedman, MBBS, PhD, and Nicole Lowres, BPhty, PhD, University of Sydney, Australia.

LOOP was partially supported by Medtronic. Dr. Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. Disclosures for the other authors are in the report. Dr. Freedman reports grants to the Heart Research Institute, speakers fees and nonfinancial support from the Bristol-Myers Squibb–Pfizer Alliance, speakers fees and nonfinancial support from Daiichi Sankyo, nonfinancial support from AliveCor, and speakers fees and nonfinancial support from Omron unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation. Dr. Lowres reports grants to the Heart Research Institute from the Bristol-Myers Squibb–Pfizer Alliance unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation.

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

Perhaps short, asymptomatic bouts of atrial fibrillation (AFib) that show up on long-term, continuous monitoring aren’t worth hunting for just so oral anticoagulation (OAC) can be started, even in elderly people with other stroke risk factors.

That’s a potential message from a randomized trial that tested an AFib screening strategy relying on an implantable loop recorder (ILR) in older adults without AFib but with other stroke risk factors who were invited to participate. OAC was recommended to any participant found with even a short bout of the arrhythmia (that is, any lasting 6 minutes or longer).

More than three times as many in the monitoring group compared to a standard-care cohort were found to have AFib, and nearly all were put on OAC. In fact, monitored participants were almost three times as likely to be put on OAC (P < .0001) compared with controls.

But it didn’t make any apparent difference to outcomes. The risk for stroke or systemic embolism did not significantly differ between the two groups over more than 5 years in the trial of about 6,000 participants, called LOOP.

“This result was seen despite a high proportion of atrial fibrillation detection, and a high acceptance of anticoagulation therapy, and might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation,” contend the authors of the LOOP report, simultaneously published in The Lancet and presented Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021.

“The rates of bleeding were modest, despite the low threshold for anticoagulation,” and was not significantly different between the two groups, Jesper H. Svendsen, MD, DMSc, Copenhagen University Hospital, Denmark, said at a media briefing before his presentation of the trial at the congress. He is lead author on the Lancet report.

At least 6 minutes of AFib was identified in more than 30% of the ILR-monitored patients, and about 90% of those were started on OAC, Dr. Svendsen observed.

But one take-home message from LOOP, he said in an interview, is that “short-lasting episodes” of AFib do not necessarily pose an untoward risk for stroke compared with AFib revealed by intermittent monitoring, which “primarily identifies longer-lasting atrial fibrillation episodes. So short-lasting episodes are probably not as serious as long-lasting.”

The LOOP trial “teaches us that perhaps short-lasting asymptomatic episodes may not benefit from being screened or found,” said Stefan James, MD, PhD, Uppsala University, Sweden. However, that may not be the case when the monitored individual is symptomatic or has longer-lasting AFib episodes, he said in an interview. “But certainly, this study teaches us that we need to understand much better the relationship between short episodes versus symptoms versus medical outcomes.”

In LOOP, 6,004 people aged 70-90 years without AFib but with at least one other stroke risk factor, which could include hypertension, diabetes, a history of stroke, or heart failure, were implanted with an ILR, the Reveal LINQ (Medtronic).

They were randomly assigned at four centers in Denmark to a monitoring group or a usual care group in a 1:3 ratio. Overwhelmingly, most had hypertension. Almost half the population were women.

OAC was recommended for all persons in the monitoring group who showed an episode of AFib lasting at least 6 minutes.

Atrial fibrillation was diagnosed in 31.8% of the 1,501 participants in the monitored group and 12.2% of the 4,503 assigned to usual care, for a hazard ratio (HR) of 3.17 (95% confidence interval, 2.81-3.59; P < .0001).

OAC was started in 29.7% of monitored participants and 13.1% of the control cohort, for an HR of 2.72 (95% CI, 2.41-3.08; P < .0001).

There were 315 strokes and three systemic arterial embolisms observed in the entire trial, for primary endpoint rates of 4.5% in the ILR monitoring group and 5.6% in the control group (HR, 0.80; 95% CI, 0.61-1.05; P = .11). Adding transient ischemic attack (TIA) or cardiovascular death to the endpoint did not make for a significant difference. The rates of major bleeding were 4.3% and 3.5%, respectively (P = .11).

“In general, the findings were consistent across subgroups,” including by age, sex, diabetes and heart failure status, stroke history, antiplatelet therapy, renal function, and even CHA2DS2–VASc score, Dr. Svendsen noted.

But, he said, participants in the highest tertile for baseline systolic blood pressure (BP), at least 157 mm Hg, “seemed to benefit from being screened,” with a 49% reduction in risk for the primary endpoint (P = .0066). The interaction between systolic BP and outcome was significant (P = .007).

Only 9.3% of participants in LOOP did not have a baseline diagnosis of hypertension and so had to have another risk factor to enroll, the published report notes. However, the significant interaction with systolic BP “suggests that patients with dysregulated hypertension could benefit from this type of screening and concomitant anticoagulation.”

“There is a tight association between our primary endpoint and hypertension,” Dr. Svendsen said in an interview. “But I think it’s very important to say that this subgroup analysis is only hypothesis-generating.”

An editorial accompanying the LOOP publication suggests, in line with Dr. Svendsen’s proposal, that “shorter atrial fibrillation episodes found by long-term ILRs might not have the same stroke risk as atrial fibrillation detected through single-timepoint or less intense monitoring.”

If much of the paroxysmal AFib observed in LOOP and other studies with similar monitoring methods “is not the actual cause of stroke and is instead predominantly a risk marker, further research is warranted to establish whether a different screening focus and treatment paradigm are required to prevent stroke and other vascular brain injury related to atrial fibrillation,” wrote editorialists Ben Freedman, MBBS, PhD, and Nicole Lowres, BPhty, PhD, University of Sydney, Australia.

LOOP was partially supported by Medtronic. Dr. Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. Disclosures for the other authors are in the report. Dr. Freedman reports grants to the Heart Research Institute, speakers fees and nonfinancial support from the Bristol-Myers Squibb–Pfizer Alliance, speakers fees and nonfinancial support from Daiichi Sankyo, nonfinancial support from AliveCor, and speakers fees and nonfinancial support from Omron unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation. Dr. Lowres reports grants to the Heart Research Institute from the Bristol-Myers Squibb–Pfizer Alliance unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation.

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

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, a new landmark study shows.

jirkaejc/Getty Images

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention,” Dr. Neal concluded. “This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical,” he added.

Addressing the issue of whether these results are generalizable to other populations, Dr. Neal said, “We believe the results are relevant to everyone who eats salt.

“The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations,” he said. “Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this.”

Commentators at the ESC presentation lauded the study as “magnificent,” with “extraordinary” results and “very powerful implications.”

Designated discussant, hypertension expert Bryan Williams, MD, University College London, said the SSaSS was “probably the most important study with regards to public health that we will see.” He described the reductions in stroke, cardiovascular events, and death as “extraordinary for such a simple intervention.”

Dr. Williams added: “Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin.”

He also highlighted the large number of events in the trial. “This was a large, pragmatic, long-duration study in a high-risk population, and with 5,000 cardiovascular events it gives enormous power to show benefits.”

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford (England), said the SSaSS “will change the way we think about salt and be remembered for years to come.”

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

“For patients with diabetes, this is a really important intervention,” he stated.

However, an editorial accompanying the NEJM publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with hyperkalemia were not studied.

She also noted that because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained.

“Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability,” she concluded.

Cluster-randomized trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had uncontrolled hypertension. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (roughly 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1,000 person-years in the salt substitute group vs. 33.65 events per 1,000 person-years with regular salt (rate ratio, 0.86; 95% confidence interval, 0.77-0.96; P = .006).

The rates of major cardiovascular events were 49.09 events per 1,000 person-years in the salt substitute group vs. 56.29 events per 1,000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80-0.94; P < .001).

And the rate of death was 39.28 events per 1,000 person-years with the salt substitute vs. 44.61 events per 1,000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82-0.95; P < .001).

The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1,000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P = .76).

Dr. Neal reported that 7%-8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.
 

Food manufacturers must make changes

Dr. Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he said he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt – salt added at home at the time of cooking for preservation of food or seasoning. “This is salt that is easy to replace with salt substitute,” Dr. Neal noted.

“There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt –  mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute.”

He pointed out that salt substitute is low cost and is easy to manufacture. “Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch.”

Dr. Neal said the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

“This study provides strong evidence to take to the food industry,” he concluded. “We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes.”

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Dr. Neal reports no disclosures. Dr. Ingelfinger is employed by the New England Journal of Medicine as deputy editor.

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

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, a new landmark study shows.

jirkaejc/Getty Images

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention,” Dr. Neal concluded. “This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical,” he added.

Addressing the issue of whether these results are generalizable to other populations, Dr. Neal said, “We believe the results are relevant to everyone who eats salt.

“The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations,” he said. “Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this.”

Commentators at the ESC presentation lauded the study as “magnificent,” with “extraordinary” results and “very powerful implications.”

Designated discussant, hypertension expert Bryan Williams, MD, University College London, said the SSaSS was “probably the most important study with regards to public health that we will see.” He described the reductions in stroke, cardiovascular events, and death as “extraordinary for such a simple intervention.”

Dr. Williams added: “Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin.”

He also highlighted the large number of events in the trial. “This was a large, pragmatic, long-duration study in a high-risk population, and with 5,000 cardiovascular events it gives enormous power to show benefits.”

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford (England), said the SSaSS “will change the way we think about salt and be remembered for years to come.”

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

“For patients with diabetes, this is a really important intervention,” he stated.

However, an editorial accompanying the NEJM publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with hyperkalemia were not studied.

She also noted that because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained.

“Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability,” she concluded.

Cluster-randomized trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had uncontrolled hypertension. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (roughly 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1,000 person-years in the salt substitute group vs. 33.65 events per 1,000 person-years with regular salt (rate ratio, 0.86; 95% confidence interval, 0.77-0.96; P = .006).

The rates of major cardiovascular events were 49.09 events per 1,000 person-years in the salt substitute group vs. 56.29 events per 1,000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80-0.94; P < .001).

And the rate of death was 39.28 events per 1,000 person-years with the salt substitute vs. 44.61 events per 1,000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82-0.95; P < .001).

The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1,000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P = .76).

Dr. Neal reported that 7%-8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.
 

Food manufacturers must make changes

Dr. Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he said he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt – salt added at home at the time of cooking for preservation of food or seasoning. “This is salt that is easy to replace with salt substitute,” Dr. Neal noted.

“There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt –  mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute.”

He pointed out that salt substitute is low cost and is easy to manufacture. “Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch.”

Dr. Neal said the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

“This study provides strong evidence to take to the food industry,” he concluded. “We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes.”

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Dr. Neal reports no disclosures. Dr. Ingelfinger is employed by the New England Journal of Medicine as deputy editor.

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

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, a new landmark study shows.

jirkaejc/Getty Images

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention,” Dr. Neal concluded. “This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical,” he added.

Addressing the issue of whether these results are generalizable to other populations, Dr. Neal said, “We believe the results are relevant to everyone who eats salt.

“The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations,” he said. “Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this.”

Commentators at the ESC presentation lauded the study as “magnificent,” with “extraordinary” results and “very powerful implications.”

Designated discussant, hypertension expert Bryan Williams, MD, University College London, said the SSaSS was “probably the most important study with regards to public health that we will see.” He described the reductions in stroke, cardiovascular events, and death as “extraordinary for such a simple intervention.”

Dr. Williams added: “Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin.”

He also highlighted the large number of events in the trial. “This was a large, pragmatic, long-duration study in a high-risk population, and with 5,000 cardiovascular events it gives enormous power to show benefits.”

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford (England), said the SSaSS “will change the way we think about salt and be remembered for years to come.”

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

“For patients with diabetes, this is a really important intervention,” he stated.

However, an editorial accompanying the NEJM publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with hyperkalemia were not studied.

She also noted that because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained.

“Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability,” she concluded.

Cluster-randomized trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had uncontrolled hypertension. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (roughly 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1,000 person-years in the salt substitute group vs. 33.65 events per 1,000 person-years with regular salt (rate ratio, 0.86; 95% confidence interval, 0.77-0.96; P = .006).

The rates of major cardiovascular events were 49.09 events per 1,000 person-years in the salt substitute group vs. 56.29 events per 1,000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80-0.94; P < .001).

And the rate of death was 39.28 events per 1,000 person-years with the salt substitute vs. 44.61 events per 1,000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82-0.95; P < .001).

The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1,000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P = .76).

Dr. Neal reported that 7%-8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.
 

Food manufacturers must make changes

Dr. Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he said he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt – salt added at home at the time of cooking for preservation of food or seasoning. “This is salt that is easy to replace with salt substitute,” Dr. Neal noted.

“There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt –  mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute.”

He pointed out that salt substitute is low cost and is easy to manufacture. “Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch.”

Dr. Neal said the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

“This study provides strong evidence to take to the food industry,” he concluded. “We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes.”

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Dr. Neal reports no disclosures. Dr. Ingelfinger is employed by the New England Journal of Medicine as deputy editor.

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

Among middle-aged people without heart disease, drinking up to three cups of coffee per day was linked with a lower risk for stroke or death over the next decade, along with better heart structure and function, in a large, observational study.

S_Bachstroem/Getty Images

Specifically, light-to-moderate coffee drinking, defined as 0.5 to 3 cups per day, was associated with a 21% lower risk for stroke, a 17% lower risk for death from cardiovascular disease (CVD), and a 12% lower risk for death from all causes, as well as more favorable cardiac MRI findings, compared with nondrinkers (< 0.5 cup per day) during a median 11-year follow-up.

Heavy coffee drinkers, defined as those consuming more than three cups per day, on the other hand, likewise had more favorable cardiac MRI findings, but with similar (not lower) rates of stroke and CVD or all-cause mortality compared with nondrinkers.

Judit Simon, MD, presented these findings, from close to 500,000 participants in the UK Biobank study, at a press conference before an e-poster session at the virtual annual congress of the European Society of Cardiology.

“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” Dr. Simon, a PhD student at the Heart and Vascular Centre, Semmelweis University, Budapest, Hungary, said in an ESC press release.

The results “suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years,” she said.

The imaging analysis showed that “compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” Dr. Simon continued, “consistent with reversing the detrimental effects of aging on the heart.”

“The observed benefits might be partly explained by positive alterations in cardiac structure and function,” she speculated, adding that further studies are needed to explain the underlying mechanisms.

Instant coffee most popular

In this population, the coffee drinkers mostly drank instant coffee (55%), followed by filtered/ground (23%), decaffeinated (20%), or other types of coffee (2%), Dr. Simon said in an interview.

Risk for myocardial infarction (MI) or heart failure did not significantly differ for different categories of coffee intake, she added. The researchers did not study the effect of coffee consumption on atrial fibrillation (AF), she noted. 

Study limitations, Dr. Simon acknowledged, include that it was observational, so it cannot show causation, and that coffee consumption was self-reported in a questionnaire.

Invited to comment, Alice H. Lichtenstein, DSc, who was not involved with the research, said, “Consistent with prior data, this new study indicates there is no adverse effect of coffee consumption on cardiovascular health and there may be a benefit.”

However, “because of the nature of the data, it would not be recommended that an individual starting drinking coffee to improve cardiovascular health,” added Dr. Lichtenstein, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston.

But if people already drink coffee, “it is fine to continue, assuming that the coffee drinks are not high in added sugar and cream,” she said in an interview.
 

Coffee intake, CVD outcomes, and heart structure

To study the relationship between coffee intake and incident MI, stroke, and death, as well as heart structure, the researchers examined data from the UK Biobank, which recruited 500,000 people aged 40-69 years in 2006-2010 from across the United Kingdom.

They identified 468,629 participants with no signs of heart disease at recruitment and an average age of 56 years, of whom 56% were women.

The participants were divided into three groups based on usual coffee intake: none (22% of participants), light-to-moderate (58%), and high (20%).

Median tea intake was three cups per day overall, four cups per day in noncoffee drinkers, three cups per day in light-to-moderate coffee drinkers, and one cup per day in high coffee drinkers.

Compared to not drinking coffee, light-to-moderate coffee consumption was associated with lower risks for all-cause death (hazard ratio [HR], 0.88; P < .001), CVD death (HR, 0.83; P = .006), and stroke (HR, 0.79; P = .037), over a median follow-up of 11 years, after adjustment for sex; weight; height; smoking status; physical activity; high blood pressure; diabetes; cholesterol level; socioeconomic status; and usual intake of alcohol, meat, tea, fruit, and vegetables.  

In the 30,650 participants who had cardiac MRI data, the study found that compared with not drinking coffee, both light-to-moderate and high coffee consumption were associated with significantly increased left and right ventricular end-systolic and end-diastolic volumes, and with greater left ventricular mass (all P < .001).

These differences were small but significant, Dr. Simon stressed, because this was a cohort of healthy patients who did not have CVD (heart failure, MI, stroke, AF) at baseline, although some had hypertension or diabetes.

Press conference chairperson, Steen Dalby Kristensen, MD, professor and cardiologist, Aarhus University Hospital, Denmark, a coffee lover himself, wanted to know if an amount such as two, three, or four cups of coffee was optimal to see these heart benefits, and whether there were differences in benefits seen with drinking different types of coffee.

The analysis did not identify an optimal coffee intake, Dr. Simon said. Compared with not drinking coffee, she continued, drinking instant coffee was associated with a lower risk for all-cause mortality, but not CVD mortality or stroke.

Drinking filtered coffee was associated with lower risks for all three outcomes, but there was no significant difference in risk for MI. Drinking decaffeinated coffee was associated with a lower risk for all-cause and CVD mortality.

“Decaffeinated coffee contains a small amount of caffeine,” Dr. Simon pointed out. “Something other than caffeine might have this protective impact,” she suggested.

The researchers and Dr. Lichtenstein declared having no relevant financial disclosures.  

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

Among middle-aged people without heart disease, drinking up to three cups of coffee per day was linked with a lower risk for stroke or death over the next decade, along with better heart structure and function, in a large, observational study.

S_Bachstroem/Getty Images

Specifically, light-to-moderate coffee drinking, defined as 0.5 to 3 cups per day, was associated with a 21% lower risk for stroke, a 17% lower risk for death from cardiovascular disease (CVD), and a 12% lower risk for death from all causes, as well as more favorable cardiac MRI findings, compared with nondrinkers (< 0.5 cup per day) during a median 11-year follow-up.

Heavy coffee drinkers, defined as those consuming more than three cups per day, on the other hand, likewise had more favorable cardiac MRI findings, but with similar (not lower) rates of stroke and CVD or all-cause mortality compared with nondrinkers.

Judit Simon, MD, presented these findings, from close to 500,000 participants in the UK Biobank study, at a press conference before an e-poster session at the virtual annual congress of the European Society of Cardiology.

“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” Dr. Simon, a PhD student at the Heart and Vascular Centre, Semmelweis University, Budapest, Hungary, said in an ESC press release.

The results “suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years,” she said.

The imaging analysis showed that “compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” Dr. Simon continued, “consistent with reversing the detrimental effects of aging on the heart.”

“The observed benefits might be partly explained by positive alterations in cardiac structure and function,” she speculated, adding that further studies are needed to explain the underlying mechanisms.

Instant coffee most popular

In this population, the coffee drinkers mostly drank instant coffee (55%), followed by filtered/ground (23%), decaffeinated (20%), or other types of coffee (2%), Dr. Simon said in an interview.

Risk for myocardial infarction (MI) or heart failure did not significantly differ for different categories of coffee intake, she added. The researchers did not study the effect of coffee consumption on atrial fibrillation (AF), she noted. 

Study limitations, Dr. Simon acknowledged, include that it was observational, so it cannot show causation, and that coffee consumption was self-reported in a questionnaire.

Invited to comment, Alice H. Lichtenstein, DSc, who was not involved with the research, said, “Consistent with prior data, this new study indicates there is no adverse effect of coffee consumption on cardiovascular health and there may be a benefit.”

However, “because of the nature of the data, it would not be recommended that an individual starting drinking coffee to improve cardiovascular health,” added Dr. Lichtenstein, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston.

But if people already drink coffee, “it is fine to continue, assuming that the coffee drinks are not high in added sugar and cream,” she said in an interview.
 

Coffee intake, CVD outcomes, and heart structure

To study the relationship between coffee intake and incident MI, stroke, and death, as well as heart structure, the researchers examined data from the UK Biobank, which recruited 500,000 people aged 40-69 years in 2006-2010 from across the United Kingdom.

They identified 468,629 participants with no signs of heart disease at recruitment and an average age of 56 years, of whom 56% were women.

The participants were divided into three groups based on usual coffee intake: none (22% of participants), light-to-moderate (58%), and high (20%).

Median tea intake was three cups per day overall, four cups per day in noncoffee drinkers, three cups per day in light-to-moderate coffee drinkers, and one cup per day in high coffee drinkers.

Compared to not drinking coffee, light-to-moderate coffee consumption was associated with lower risks for all-cause death (hazard ratio [HR], 0.88; P < .001), CVD death (HR, 0.83; P = .006), and stroke (HR, 0.79; P = .037), over a median follow-up of 11 years, after adjustment for sex; weight; height; smoking status; physical activity; high blood pressure; diabetes; cholesterol level; socioeconomic status; and usual intake of alcohol, meat, tea, fruit, and vegetables.  

In the 30,650 participants who had cardiac MRI data, the study found that compared with not drinking coffee, both light-to-moderate and high coffee consumption were associated with significantly increased left and right ventricular end-systolic and end-diastolic volumes, and with greater left ventricular mass (all P < .001).

These differences were small but significant, Dr. Simon stressed, because this was a cohort of healthy patients who did not have CVD (heart failure, MI, stroke, AF) at baseline, although some had hypertension or diabetes.

Press conference chairperson, Steen Dalby Kristensen, MD, professor and cardiologist, Aarhus University Hospital, Denmark, a coffee lover himself, wanted to know if an amount such as two, three, or four cups of coffee was optimal to see these heart benefits, and whether there were differences in benefits seen with drinking different types of coffee.

The analysis did not identify an optimal coffee intake, Dr. Simon said. Compared with not drinking coffee, she continued, drinking instant coffee was associated with a lower risk for all-cause mortality, but not CVD mortality or stroke.

Drinking filtered coffee was associated with lower risks for all three outcomes, but there was no significant difference in risk for MI. Drinking decaffeinated coffee was associated with a lower risk for all-cause and CVD mortality.

“Decaffeinated coffee contains a small amount of caffeine,” Dr. Simon pointed out. “Something other than caffeine might have this protective impact,” she suggested.

The researchers and Dr. Lichtenstein declared having no relevant financial disclosures.  

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

Among middle-aged people without heart disease, drinking up to three cups of coffee per day was linked with a lower risk for stroke or death over the next decade, along with better heart structure and function, in a large, observational study.

S_Bachstroem/Getty Images

Specifically, light-to-moderate coffee drinking, defined as 0.5 to 3 cups per day, was associated with a 21% lower risk for stroke, a 17% lower risk for death from cardiovascular disease (CVD), and a 12% lower risk for death from all causes, as well as more favorable cardiac MRI findings, compared with nondrinkers (< 0.5 cup per day) during a median 11-year follow-up.

Heavy coffee drinkers, defined as those consuming more than three cups per day, on the other hand, likewise had more favorable cardiac MRI findings, but with similar (not lower) rates of stroke and CVD or all-cause mortality compared with nondrinkers.

Judit Simon, MD, presented these findings, from close to 500,000 participants in the UK Biobank study, at a press conference before an e-poster session at the virtual annual congress of the European Society of Cardiology.

“To our knowledge, this is the largest study to systematically assess the cardiovascular effects of regular coffee consumption in a population without diagnosed heart disease,” Dr. Simon, a PhD student at the Heart and Vascular Centre, Semmelweis University, Budapest, Hungary, said in an ESC press release.

The results “suggest that regular coffee consumption is safe, as even high daily intake was not associated with adverse cardiovascular outcomes and all-cause mortality after a follow-up of 10 to 15 years,” she said.

The imaging analysis showed that “compared with participants who did not drink coffee regularly, daily consumers had healthier sized and better functioning hearts,” Dr. Simon continued, “consistent with reversing the detrimental effects of aging on the heart.”

“The observed benefits might be partly explained by positive alterations in cardiac structure and function,” she speculated, adding that further studies are needed to explain the underlying mechanisms.

Instant coffee most popular

In this population, the coffee drinkers mostly drank instant coffee (55%), followed by filtered/ground (23%), decaffeinated (20%), or other types of coffee (2%), Dr. Simon said in an interview.

Risk for myocardial infarction (MI) or heart failure did not significantly differ for different categories of coffee intake, she added. The researchers did not study the effect of coffee consumption on atrial fibrillation (AF), she noted. 

Study limitations, Dr. Simon acknowledged, include that it was observational, so it cannot show causation, and that coffee consumption was self-reported in a questionnaire.

Invited to comment, Alice H. Lichtenstein, DSc, who was not involved with the research, said, “Consistent with prior data, this new study indicates there is no adverse effect of coffee consumption on cardiovascular health and there may be a benefit.”

However, “because of the nature of the data, it would not be recommended that an individual starting drinking coffee to improve cardiovascular health,” added Dr. Lichtenstein, director and senior scientist at the Cardiovascular Nutrition Laboratory at Tufts University, Boston.

But if people already drink coffee, “it is fine to continue, assuming that the coffee drinks are not high in added sugar and cream,” she said in an interview.
 

Coffee intake, CVD outcomes, and heart structure

To study the relationship between coffee intake and incident MI, stroke, and death, as well as heart structure, the researchers examined data from the UK Biobank, which recruited 500,000 people aged 40-69 years in 2006-2010 from across the United Kingdom.

They identified 468,629 participants with no signs of heart disease at recruitment and an average age of 56 years, of whom 56% were women.

The participants were divided into three groups based on usual coffee intake: none (22% of participants), light-to-moderate (58%), and high (20%).

Median tea intake was three cups per day overall, four cups per day in noncoffee drinkers, three cups per day in light-to-moderate coffee drinkers, and one cup per day in high coffee drinkers.

Compared to not drinking coffee, light-to-moderate coffee consumption was associated with lower risks for all-cause death (hazard ratio [HR], 0.88; P < .001), CVD death (HR, 0.83; P = .006), and stroke (HR, 0.79; P = .037), over a median follow-up of 11 years, after adjustment for sex; weight; height; smoking status; physical activity; high blood pressure; diabetes; cholesterol level; socioeconomic status; and usual intake of alcohol, meat, tea, fruit, and vegetables.  

In the 30,650 participants who had cardiac MRI data, the study found that compared with not drinking coffee, both light-to-moderate and high coffee consumption were associated with significantly increased left and right ventricular end-systolic and end-diastolic volumes, and with greater left ventricular mass (all P < .001).

These differences were small but significant, Dr. Simon stressed, because this was a cohort of healthy patients who did not have CVD (heart failure, MI, stroke, AF) at baseline, although some had hypertension or diabetes.

Press conference chairperson, Steen Dalby Kristensen, MD, professor and cardiologist, Aarhus University Hospital, Denmark, a coffee lover himself, wanted to know if an amount such as two, three, or four cups of coffee was optimal to see these heart benefits, and whether there were differences in benefits seen with drinking different types of coffee.

The analysis did not identify an optimal coffee intake, Dr. Simon said. Compared with not drinking coffee, she continued, drinking instant coffee was associated with a lower risk for all-cause mortality, but not CVD mortality or stroke.

Drinking filtered coffee was associated with lower risks for all three outcomes, but there was no significant difference in risk for MI. Drinking decaffeinated coffee was associated with a lower risk for all-cause and CVD mortality.

“Decaffeinated coffee contains a small amount of caffeine,” Dr. Simon pointed out. “Something other than caffeine might have this protective impact,” she suggested.

The researchers and Dr. Lichtenstein declared having no relevant financial disclosures.  

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

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

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

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

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

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

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

The presence of chronic kidney disease (CKD) or end-stage renal disease (ESRD) is associated with worse in-hospital and short-term outcomes after left atrial appendage (LAA) closure, a nationwide study shows.

Patients with ESRD were particularly vulnerable, having about 6.5-fold higher odds of in-hospital mortality than those without CKD and about 11.5-fold higher odds than those with CKD, even after adjustment for potential confounders.

Patients with CKD had higher rates of stroke or transient ischemic attack (TIA) and more short-term readmissions for bleeding, Keerat Rai Ahuja, MD, Reading Hospital-Tower Health, West Reading, Pennsylvania, and colleagues reported August 16 in JACC: Cardiovascular Interventions.

CKD and ESRD are known to be associated with an increased risk for stroke and bleeding in patients with atrial fibrillation (AFib), yet data are limited on the safety and efficacy of LAA closure for stroke prevention in AFib patients with CKD or ESRD, they note.  

“It’s important to know about CKD and understand that there may be an association with worse levels of CKD and worse outcomes, but the data that strikes me is really that for end-stage renal disease,” Matthew Sherwood, MD, MHS, who was not involved with the study, said in an interview.

He noted that data have not been published for patients with CKD and ESRD enrolled in the pivotal PROTECT-AF and PREVAIL trials of Boston Scientific’s Watchman device or from large clinical registries such as EWOLUTION and the company’s continued access protocol registries.

Further, it’s not well understood what the best strategy is to prevent stroke in AFib patients with ESRD and whether they benefit from anticoagulation with warfarin or any of the newer agents. “Thus, it’s hard to then say: ‘Well they have worse outcomes with Watchman,’ which is true as shown in this study, but they may not have any other options based upon the lack of data for oral anticoagulants in end-stage kidney disease patients,” said Dr. Sherwood, from the Inova Heart and Vascular Institute, Falls Church, Virginia.

The lack of clarity is concerning, given rising atrial fibrillation cases and the prevalence of abnormal renal function in everyday practice. In the present study – involving 21,274 patients undergoing LAA closure between 2016 and 2017 in the Nationwide Readmissions Database – 18.6% of patients had CKD stages I to V and 2.7% had ESRD based on ICD-10 codes.

In-hospital mortality was increased only in patients with ESRD. In all, 3.3% of patients with ESRD and 0.4% of those with no CKD died in hospital (adjusted odds ratio [aOR], 6.48), as did 0.5% of patients with CKD (aOR, 11.43; both P <.001).

“These patients represent a sicker population at baseline and have an inherent greater risk for mortality in cardiac interventions, as noted in other studies of structural heart interventions,” Dr. Ahuja and colleagues write.

Patients with CKD had a higher risk for in-hospital stroke or TIA than patients with no CKD (1.8% vs. 1.3%; aOR, 1.35; P = .038) and this risk continued up to 90 days after discharge (1.7% vs. 1.0%; aOR, 1.67; P = .007).

The in-hospital stroke rate was numerically higher in patients with ESRD compared with no CKD (aOR, 1.18; P = .62).

The authors point out that previous LAA closure and CKD studies have reported no differences in in-hospital or subsequent stroke/TIA rates in patients with and without CKD. Possible explanations are that patients with CKD in the present study had higher CHA2DS2-VASc scores than those without CKD (4.18 vs. 3.62) and, second, patients with CKD and AFib are known to have higher risk for thromboembolic events than those with AFib without CKD.

CKD patients were also more likely than those without CKD to experience in-hospital acute kidney injury or hemodialysis (aOR, 5.02; P <.001).

CKD has been shown to be independently associated with acute kidney injury (AKI) after LAA closure. AKI may have long-term thromboembolic consequences, the authors suggest, with one study reporting higher stroke risk at midterm follow-up in patients with AKI.

“As with other cardiac interventions in patients with CKD, efforts should be made to optimize preoperative renal function, minimize contrast volume, and avoid abrupt hemodynamic changes such as hypotension during the procedure to prevent AKI,” Dr. Ahuja and colleagues write.

Patients with CKD and ESRD had longer index length of stay than those without CKD but had similar rates of other in-hospital complications, such as systemic embolization, bleeding/transfusion, vascular complications, and pericardial tamponade requiring intervention.

Among the short-term outcomes, 30- and 90-day all-cause readmissions were increased in patients with CKD and ESRD compared with those without CKD, and 30-day bleeding readmissions were increased within the CKD cohort.

“With Watchman and left atrial appendage closure, what we see is that they have higher rates of readmission and other problems,” Dr. Sherwood said. “I think we understand that that’s probably related not to the procedure itself, not because the Watchman doesn’t work for end-stage kidney disease, but because the patients themselves are likely higher risk.”

Commonly used risk scores for atrial fibrillation, however, don’t take into account advanced kidney disease, he added.

Besides the inherent limitations of observational studies, Dr. Sherwood and the authors point to the lack of laboratory variables and procedural variables in the database, the fact that CKD was defined using ICD-10 codes, that outcomes were not clinically adjudicated, that unmeasured confounders likely still exist, and that long-term follow-up is lacking.

Dr. Sherwood, who wrote an editorial accompanying the study, said that the release of outcomes data from CKD and ESRD patients in the major clinical trials would be helpful going forward, as would possible involvement with the Kidney Disease Improving Global Outcomes organization.

“One of the main points of this study is that we just need a lot more research diving into this patient population,” he said.

The authors report no relevant financial relationships. Dr. Sherwood reports honoraria from Janssen and Medtronic. Editorial coauthor Sean Pokorney reports research grant support from Gilead, Boston Scientific, Pfizer, Bristol Myers Squibb, Janssen, and the Food and Drug Administration; and advisory board, consulting, and honoraria supports from Medtronic, Boston Scientific, Pfizer, Bristol Myers Squibb, Philips, and Zoll.

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

The presence of chronic kidney disease (CKD) or end-stage renal disease (ESRD) is associated with worse in-hospital and short-term outcomes after left atrial appendage (LAA) closure, a nationwide study shows.

Patients with ESRD were particularly vulnerable, having about 6.5-fold higher odds of in-hospital mortality than those without CKD and about 11.5-fold higher odds than those with CKD, even after adjustment for potential confounders.

Patients with CKD had higher rates of stroke or transient ischemic attack (TIA) and more short-term readmissions for bleeding, Keerat Rai Ahuja, MD, Reading Hospital-Tower Health, West Reading, Pennsylvania, and colleagues reported August 16 in JACC: Cardiovascular Interventions.

CKD and ESRD are known to be associated with an increased risk for stroke and bleeding in patients with atrial fibrillation (AFib), yet data are limited on the safety and efficacy of LAA closure for stroke prevention in AFib patients with CKD or ESRD, they note.  

“It’s important to know about CKD and understand that there may be an association with worse levels of CKD and worse outcomes, but the data that strikes me is really that for end-stage renal disease,” Matthew Sherwood, MD, MHS, who was not involved with the study, said in an interview.

He noted that data have not been published for patients with CKD and ESRD enrolled in the pivotal PROTECT-AF and PREVAIL trials of Boston Scientific’s Watchman device or from large clinical registries such as EWOLUTION and the company’s continued access protocol registries.

Further, it’s not well understood what the best strategy is to prevent stroke in AFib patients with ESRD and whether they benefit from anticoagulation with warfarin or any of the newer agents. “Thus, it’s hard to then say: ‘Well they have worse outcomes with Watchman,’ which is true as shown in this study, but they may not have any other options based upon the lack of data for oral anticoagulants in end-stage kidney disease patients,” said Dr. Sherwood, from the Inova Heart and Vascular Institute, Falls Church, Virginia.

The lack of clarity is concerning, given rising atrial fibrillation cases and the prevalence of abnormal renal function in everyday practice. In the present study – involving 21,274 patients undergoing LAA closure between 2016 and 2017 in the Nationwide Readmissions Database – 18.6% of patients had CKD stages I to V and 2.7% had ESRD based on ICD-10 codes.

In-hospital mortality was increased only in patients with ESRD. In all, 3.3% of patients with ESRD and 0.4% of those with no CKD died in hospital (adjusted odds ratio [aOR], 6.48), as did 0.5% of patients with CKD (aOR, 11.43; both P <.001).

“These patients represent a sicker population at baseline and have an inherent greater risk for mortality in cardiac interventions, as noted in other studies of structural heart interventions,” Dr. Ahuja and colleagues write.

Patients with CKD had a higher risk for in-hospital stroke or TIA than patients with no CKD (1.8% vs. 1.3%; aOR, 1.35; P = .038) and this risk continued up to 90 days after discharge (1.7% vs. 1.0%; aOR, 1.67; P = .007).

The in-hospital stroke rate was numerically higher in patients with ESRD compared with no CKD (aOR, 1.18; P = .62).

The authors point out that previous LAA closure and CKD studies have reported no differences in in-hospital or subsequent stroke/TIA rates in patients with and without CKD. Possible explanations are that patients with CKD in the present study had higher CHA2DS2-VASc scores than those without CKD (4.18 vs. 3.62) and, second, patients with CKD and AFib are known to have higher risk for thromboembolic events than those with AFib without CKD.

CKD patients were also more likely than those without CKD to experience in-hospital acute kidney injury or hemodialysis (aOR, 5.02; P <.001).

CKD has been shown to be independently associated with acute kidney injury (AKI) after LAA closure. AKI may have long-term thromboembolic consequences, the authors suggest, with one study reporting higher stroke risk at midterm follow-up in patients with AKI.

“As with other cardiac interventions in patients with CKD, efforts should be made to optimize preoperative renal function, minimize contrast volume, and avoid abrupt hemodynamic changes such as hypotension during the procedure to prevent AKI,” Dr. Ahuja and colleagues write.

Patients with CKD and ESRD had longer index length of stay than those without CKD but had similar rates of other in-hospital complications, such as systemic embolization, bleeding/transfusion, vascular complications, and pericardial tamponade requiring intervention.

Among the short-term outcomes, 30- and 90-day all-cause readmissions were increased in patients with CKD and ESRD compared with those without CKD, and 30-day bleeding readmissions were increased within the CKD cohort.

“With Watchman and left atrial appendage closure, what we see is that they have higher rates of readmission and other problems,” Dr. Sherwood said. “I think we understand that that’s probably related not to the procedure itself, not because the Watchman doesn’t work for end-stage kidney disease, but because the patients themselves are likely higher risk.”

Commonly used risk scores for atrial fibrillation, however, don’t take into account advanced kidney disease, he added.

Besides the inherent limitations of observational studies, Dr. Sherwood and the authors point to the lack of laboratory variables and procedural variables in the database, the fact that CKD was defined using ICD-10 codes, that outcomes were not clinically adjudicated, that unmeasured confounders likely still exist, and that long-term follow-up is lacking.

Dr. Sherwood, who wrote an editorial accompanying the study, said that the release of outcomes data from CKD and ESRD patients in the major clinical trials would be helpful going forward, as would possible involvement with the Kidney Disease Improving Global Outcomes organization.

“One of the main points of this study is that we just need a lot more research diving into this patient population,” he said.

The authors report no relevant financial relationships. Dr. Sherwood reports honoraria from Janssen and Medtronic. Editorial coauthor Sean Pokorney reports research grant support from Gilead, Boston Scientific, Pfizer, Bristol Myers Squibb, Janssen, and the Food and Drug Administration; and advisory board, consulting, and honoraria supports from Medtronic, Boston Scientific, Pfizer, Bristol Myers Squibb, Philips, and Zoll.

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

The presence of chronic kidney disease (CKD) or end-stage renal disease (ESRD) is associated with worse in-hospital and short-term outcomes after left atrial appendage (LAA) closure, a nationwide study shows.

Patients with ESRD were particularly vulnerable, having about 6.5-fold higher odds of in-hospital mortality than those without CKD and about 11.5-fold higher odds than those with CKD, even after adjustment for potential confounders.

Patients with CKD had higher rates of stroke or transient ischemic attack (TIA) and more short-term readmissions for bleeding, Keerat Rai Ahuja, MD, Reading Hospital-Tower Health, West Reading, Pennsylvania, and colleagues reported August 16 in JACC: Cardiovascular Interventions.

CKD and ESRD are known to be associated with an increased risk for stroke and bleeding in patients with atrial fibrillation (AFib), yet data are limited on the safety and efficacy of LAA closure for stroke prevention in AFib patients with CKD or ESRD, they note.  

“It’s important to know about CKD and understand that there may be an association with worse levels of CKD and worse outcomes, but the data that strikes me is really that for end-stage renal disease,” Matthew Sherwood, MD, MHS, who was not involved with the study, said in an interview.

He noted that data have not been published for patients with CKD and ESRD enrolled in the pivotal PROTECT-AF and PREVAIL trials of Boston Scientific’s Watchman device or from large clinical registries such as EWOLUTION and the company’s continued access protocol registries.

Further, it’s not well understood what the best strategy is to prevent stroke in AFib patients with ESRD and whether they benefit from anticoagulation with warfarin or any of the newer agents. “Thus, it’s hard to then say: ‘Well they have worse outcomes with Watchman,’ which is true as shown in this study, but they may not have any other options based upon the lack of data for oral anticoagulants in end-stage kidney disease patients,” said Dr. Sherwood, from the Inova Heart and Vascular Institute, Falls Church, Virginia.

The lack of clarity is concerning, given rising atrial fibrillation cases and the prevalence of abnormal renal function in everyday practice. In the present study – involving 21,274 patients undergoing LAA closure between 2016 and 2017 in the Nationwide Readmissions Database – 18.6% of patients had CKD stages I to V and 2.7% had ESRD based on ICD-10 codes.

In-hospital mortality was increased only in patients with ESRD. In all, 3.3% of patients with ESRD and 0.4% of those with no CKD died in hospital (adjusted odds ratio [aOR], 6.48), as did 0.5% of patients with CKD (aOR, 11.43; both P <.001).

“These patients represent a sicker population at baseline and have an inherent greater risk for mortality in cardiac interventions, as noted in other studies of structural heart interventions,” Dr. Ahuja and colleagues write.

Patients with CKD had a higher risk for in-hospital stroke or TIA than patients with no CKD (1.8% vs. 1.3%; aOR, 1.35; P = .038) and this risk continued up to 90 days after discharge (1.7% vs. 1.0%; aOR, 1.67; P = .007).

The in-hospital stroke rate was numerically higher in patients with ESRD compared with no CKD (aOR, 1.18; P = .62).

The authors point out that previous LAA closure and CKD studies have reported no differences in in-hospital or subsequent stroke/TIA rates in patients with and without CKD. Possible explanations are that patients with CKD in the present study had higher CHA2DS2-VASc scores than those without CKD (4.18 vs. 3.62) and, second, patients with CKD and AFib are known to have higher risk for thromboembolic events than those with AFib without CKD.

CKD patients were also more likely than those without CKD to experience in-hospital acute kidney injury or hemodialysis (aOR, 5.02; P <.001).

CKD has been shown to be independently associated with acute kidney injury (AKI) after LAA closure. AKI may have long-term thromboembolic consequences, the authors suggest, with one study reporting higher stroke risk at midterm follow-up in patients with AKI.

“As with other cardiac interventions in patients with CKD, efforts should be made to optimize preoperative renal function, minimize contrast volume, and avoid abrupt hemodynamic changes such as hypotension during the procedure to prevent AKI,” Dr. Ahuja and colleagues write.

Patients with CKD and ESRD had longer index length of stay than those without CKD but had similar rates of other in-hospital complications, such as systemic embolization, bleeding/transfusion, vascular complications, and pericardial tamponade requiring intervention.

Among the short-term outcomes, 30- and 90-day all-cause readmissions were increased in patients with CKD and ESRD compared with those without CKD, and 30-day bleeding readmissions were increased within the CKD cohort.

“With Watchman and left atrial appendage closure, what we see is that they have higher rates of readmission and other problems,” Dr. Sherwood said. “I think we understand that that’s probably related not to the procedure itself, not because the Watchman doesn’t work for end-stage kidney disease, but because the patients themselves are likely higher risk.”

Commonly used risk scores for atrial fibrillation, however, don’t take into account advanced kidney disease, he added.

Besides the inherent limitations of observational studies, Dr. Sherwood and the authors point to the lack of laboratory variables and procedural variables in the database, the fact that CKD was defined using ICD-10 codes, that outcomes were not clinically adjudicated, that unmeasured confounders likely still exist, and that long-term follow-up is lacking.

Dr. Sherwood, who wrote an editorial accompanying the study, said that the release of outcomes data from CKD and ESRD patients in the major clinical trials would be helpful going forward, as would possible involvement with the Kidney Disease Improving Global Outcomes organization.

“One of the main points of this study is that we just need a lot more research diving into this patient population,” he said.

The authors report no relevant financial relationships. Dr. Sherwood reports honoraria from Janssen and Medtronic. Editorial coauthor Sean Pokorney reports research grant support from Gilead, Boston Scientific, Pfizer, Bristol Myers Squibb, Janssen, and the Food and Drug Administration; and advisory board, consulting, and honoraria supports from Medtronic, Boston Scientific, Pfizer, Bristol Myers Squibb, Philips, and Zoll.

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

Spending more free time seated combined with engaging in low physical activity is associated with an increased risk of stroke in adults aged between 40 and 60 years, according to a new analysis.

While the risk of stroke increased more than fourfold among sedentary people under the age of 60, no significant increase in risk was observed among older individuals, according to the study based on self-reported data from more than 140,000 people. This highlights the need for relevant public health messaging directed at younger people, reported lead author, Raed A. Joundi, MD, DPhil, a stroke fellow at the University of Calgary (Alta.), and colleagues, in the paper published in Stroke.

“Sedentary time has increased over the past 2 decades in the United States and Canada, particularly in the young, raising the importance of characterizing its effect on long-term health , ” the investigators wrote. “A better understanding of the risk of sedentary time specific to stroke may be important for public health campaigns to reduce sedentary behavior.” Dr. Joundi and colleagues reviewed data from the Canadian Community Health Survey, including 143,180 healthy individuals without baseline history of cancer, heart disease, or stroke. Those under the age of 40 years were also excluded from the analysis.

Excess sedentary leisure time was defined as 8 or more hours of sedentary leisure time per day, whereas low physical activity was defined as less than 3.5 metabolic equivalent hours per week. The analysis also included a range of demographic and medical covariates, such as age, sex, marital status, smoking status, presence of hypertension, and others.

After a median follow-up of 9.4 years, 2,965 stroke events occurred, with a median time from survey response of 5.6 years. Risk of stroke among individuals aged younger than 60 years who engaged in low physical activity and excess sedentary leisure time was increased 4.5-fold, compared with individuals with low physical activity who were sedentary less than 4 hours per day (fully adjusted hazard ratio, 4.50; 95% confidence interval, 1.64-12.3).
 

Findings highlight benefits of physical activity

Similar risk elevations were not observed among individuals aged 60-79 years, or those older than 80. And among people younger than 60, high physical activity appeared to eliminate the additional risk imposed by excess sedentary leisure time.

“Sedentary time is associated with higher risk of stroke in inactive individuals, but not an active individual, ” Dr. Joundi said in an interview. “So it suggests that there’s two ways to lower risk: One would be to lower your sedentary time, and the other would be to engage in physical activity.”

These interpretations are speculative, Dr. Joundi cautioned, as the study was not interventional. Even so, he said that the findings “bring the spotlight back on physical activity,” thereby aligning with previous research.

“The more you exercise, the more that relationship between sedentary time and poor health outcomes is blunted, and in fact, can be completely negated with enough physical activity,” he said.

How exactly physical activity offers such protection remains unclear, Dr. Joundi added. He speculated that regularity of exercise may be key, with each session counteracting the adverse effects of prolonged sedentary time, which may include reduced blood flow, increased insulin resistance, and inflammatory changes that can affect blood vessels.

“This study is particularly a message for younger individuals,” Dr. Joundi said, suggesting that the findings may alter behavior, as many people have witnessed, or are aware of, the long-term impacts of stroke.

“There’s a sort of social or cognitive aversion to stroke, I think, in the general population, because of how disabling it can be, and how it can lower your quality of life,” he said.
 

Subtle lifestyle changes may be enough.

For those aiming to lower their risk of stroke, Dr. Joundi suggested that subtle lifestyle changes may be enough.

“Ultimately, what we saw is that even minimal amounts of physical activity – walking 3 hours a week, for example – could blunt the impact of sedentary time,” he said. “Doing what you can, even if it’s a small amount, tends to be quite meaningful over a long period of time.”

Daniel T. Lackland, DrPH, professor of epidemiology in the department of neurology at the Medical University of South Carolina, Charleston, offered a similar takeaway, noting that small efforts can lead to great benefits.

“Less intense activity is still better than being sedentary,” he said in an interview. “For many people, if you do get up and you just walk around, move your arms around – do any kind of movement – that’s better than being sedentary.”

Dr. Lackland applauded the practicality of studying sedentary leisure time, versus overall leisure time, as many people can’t control their work environment.

“You can’t do very much about how you work your job,” Dr. Lackland said. “Sometimes we have to sit, and I guess there are things you can do – you can put a treadmill instead of a chair and that kind of thing – but more often than not, you don’t really have that choice to do something. With leisure time, though, you’re in full control. And so what do you do with your leisure time? Do you sit and watch TV, or do you engage in some type of activity? Not necessarily aerobic activity, but some type of activity that would not let you be sedentary. You want to be active as much as you possibly can.”

Dr. Joundi disclosed grant support from the Canadian Institutes of Health Research. The other investigators and Dr. Lackland reported no relevant disclosures.

Spending more free time seated combined with engaging in low physical activity is associated with an increased risk of stroke in adults aged between 40 and 60 years, according to a new analysis.

While the risk of stroke increased more than fourfold among sedentary people under the age of 60, no significant increase in risk was observed among older individuals, according to the study based on self-reported data from more than 140,000 people. This highlights the need for relevant public health messaging directed at younger people, reported lead author, Raed A. Joundi, MD, DPhil, a stroke fellow at the University of Calgary (Alta.), and colleagues, in the paper published in Stroke.

“Sedentary time has increased over the past 2 decades in the United States and Canada, particularly in the young, raising the importance of characterizing its effect on long-term health , ” the investigators wrote. “A better understanding of the risk of sedentary time specific to stroke may be important for public health campaigns to reduce sedentary behavior.” Dr. Joundi and colleagues reviewed data from the Canadian Community Health Survey, including 143,180 healthy individuals without baseline history of cancer, heart disease, or stroke. Those under the age of 40 years were also excluded from the analysis.

Excess sedentary leisure time was defined as 8 or more hours of sedentary leisure time per day, whereas low physical activity was defined as less than 3.5 metabolic equivalent hours per week. The analysis also included a range of demographic and medical covariates, such as age, sex, marital status, smoking status, presence of hypertension, and others.

After a median follow-up of 9.4 years, 2,965 stroke events occurred, with a median time from survey response of 5.6 years. Risk of stroke among individuals aged younger than 60 years who engaged in low physical activity and excess sedentary leisure time was increased 4.5-fold, compared with individuals with low physical activity who were sedentary less than 4 hours per day (fully adjusted hazard ratio, 4.50; 95% confidence interval, 1.64-12.3).
 

Findings highlight benefits of physical activity

Similar risk elevations were not observed among individuals aged 60-79 years, or those older than 80. And among people younger than 60, high physical activity appeared to eliminate the additional risk imposed by excess sedentary leisure time.

“Sedentary time is associated with higher risk of stroke in inactive individuals, but not an active individual, ” Dr. Joundi said in an interview. “So it suggests that there’s two ways to lower risk: One would be to lower your sedentary time, and the other would be to engage in physical activity.”

These interpretations are speculative, Dr. Joundi cautioned, as the study was not interventional. Even so, he said that the findings “bring the spotlight back on physical activity,” thereby aligning with previous research.

“The more you exercise, the more that relationship between sedentary time and poor health outcomes is blunted, and in fact, can be completely negated with enough physical activity,” he said.

How exactly physical activity offers such protection remains unclear, Dr. Joundi added. He speculated that regularity of exercise may be key, with each session counteracting the adverse effects of prolonged sedentary time, which may include reduced blood flow, increased insulin resistance, and inflammatory changes that can affect blood vessels.

“This study is particularly a message for younger individuals,” Dr. Joundi said, suggesting that the findings may alter behavior, as many people have witnessed, or are aware of, the long-term impacts of stroke.

“There’s a sort of social or cognitive aversion to stroke, I think, in the general population, because of how disabling it can be, and how it can lower your quality of life,” he said.
 

Subtle lifestyle changes may be enough.

For those aiming to lower their risk of stroke, Dr. Joundi suggested that subtle lifestyle changes may be enough.

“Ultimately, what we saw is that even minimal amounts of physical activity – walking 3 hours a week, for example – could blunt the impact of sedentary time,” he said. “Doing what you can, even if it’s a small amount, tends to be quite meaningful over a long period of time.”

Daniel T. Lackland, DrPH, professor of epidemiology in the department of neurology at the Medical University of South Carolina, Charleston, offered a similar takeaway, noting that small efforts can lead to great benefits.

“Less intense activity is still better than being sedentary,” he said in an interview. “For many people, if you do get up and you just walk around, move your arms around – do any kind of movement – that’s better than being sedentary.”

Dr. Lackland applauded the practicality of studying sedentary leisure time, versus overall leisure time, as many people can’t control their work environment.

“You can’t do very much about how you work your job,” Dr. Lackland said. “Sometimes we have to sit, and I guess there are things you can do – you can put a treadmill instead of a chair and that kind of thing – but more often than not, you don’t really have that choice to do something. With leisure time, though, you’re in full control. And so what do you do with your leisure time? Do you sit and watch TV, or do you engage in some type of activity? Not necessarily aerobic activity, but some type of activity that would not let you be sedentary. You want to be active as much as you possibly can.”

Dr. Joundi disclosed grant support from the Canadian Institutes of Health Research. The other investigators and Dr. Lackland reported no relevant disclosures.

Spending more free time seated combined with engaging in low physical activity is associated with an increased risk of stroke in adults aged between 40 and 60 years, according to a new analysis.

While the risk of stroke increased more than fourfold among sedentary people under the age of 60, no significant increase in risk was observed among older individuals, according to the study based on self-reported data from more than 140,000 people. This highlights the need for relevant public health messaging directed at younger people, reported lead author, Raed A. Joundi, MD, DPhil, a stroke fellow at the University of Calgary (Alta.), and colleagues, in the paper published in Stroke.

“Sedentary time has increased over the past 2 decades in the United States and Canada, particularly in the young, raising the importance of characterizing its effect on long-term health , ” the investigators wrote. “A better understanding of the risk of sedentary time specific to stroke may be important for public health campaigns to reduce sedentary behavior.” Dr. Joundi and colleagues reviewed data from the Canadian Community Health Survey, including 143,180 healthy individuals without baseline history of cancer, heart disease, or stroke. Those under the age of 40 years were also excluded from the analysis.

Excess sedentary leisure time was defined as 8 or more hours of sedentary leisure time per day, whereas low physical activity was defined as less than 3.5 metabolic equivalent hours per week. The analysis also included a range of demographic and medical covariates, such as age, sex, marital status, smoking status, presence of hypertension, and others.

After a median follow-up of 9.4 years, 2,965 stroke events occurred, with a median time from survey response of 5.6 years. Risk of stroke among individuals aged younger than 60 years who engaged in low physical activity and excess sedentary leisure time was increased 4.5-fold, compared with individuals with low physical activity who were sedentary less than 4 hours per day (fully adjusted hazard ratio, 4.50; 95% confidence interval, 1.64-12.3).
 

Findings highlight benefits of physical activity

Similar risk elevations were not observed among individuals aged 60-79 years, or those older than 80. And among people younger than 60, high physical activity appeared to eliminate the additional risk imposed by excess sedentary leisure time.

“Sedentary time is associated with higher risk of stroke in inactive individuals, but not an active individual, ” Dr. Joundi said in an interview. “So it suggests that there’s two ways to lower risk: One would be to lower your sedentary time, and the other would be to engage in physical activity.”

These interpretations are speculative, Dr. Joundi cautioned, as the study was not interventional. Even so, he said that the findings “bring the spotlight back on physical activity,” thereby aligning with previous research.

“The more you exercise, the more that relationship between sedentary time and poor health outcomes is blunted, and in fact, can be completely negated with enough physical activity,” he said.

How exactly physical activity offers such protection remains unclear, Dr. Joundi added. He speculated that regularity of exercise may be key, with each session counteracting the adverse effects of prolonged sedentary time, which may include reduced blood flow, increased insulin resistance, and inflammatory changes that can affect blood vessels.

“This study is particularly a message for younger individuals,” Dr. Joundi said, suggesting that the findings may alter behavior, as many people have witnessed, or are aware of, the long-term impacts of stroke.

“There’s a sort of social or cognitive aversion to stroke, I think, in the general population, because of how disabling it can be, and how it can lower your quality of life,” he said.
 

Subtle lifestyle changes may be enough.

For those aiming to lower their risk of stroke, Dr. Joundi suggested that subtle lifestyle changes may be enough.

“Ultimately, what we saw is that even minimal amounts of physical activity – walking 3 hours a week, for example – could blunt the impact of sedentary time,” he said. “Doing what you can, even if it’s a small amount, tends to be quite meaningful over a long period of time.”

Daniel T. Lackland, DrPH, professor of epidemiology in the department of neurology at the Medical University of South Carolina, Charleston, offered a similar takeaway, noting that small efforts can lead to great benefits.

“Less intense activity is still better than being sedentary,” he said in an interview. “For many people, if you do get up and you just walk around, move your arms around – do any kind of movement – that’s better than being sedentary.”

Dr. Lackland applauded the practicality of studying sedentary leisure time, versus overall leisure time, as many people can’t control their work environment.

“You can’t do very much about how you work your job,” Dr. Lackland said. “Sometimes we have to sit, and I guess there are things you can do – you can put a treadmill instead of a chair and that kind of thing – but more often than not, you don’t really have that choice to do something. With leisure time, though, you’re in full control. And so what do you do with your leisure time? Do you sit and watch TV, or do you engage in some type of activity? Not necessarily aerobic activity, but some type of activity that would not let you be sedentary. You want to be active as much as you possibly can.”

Dr. Joundi disclosed grant support from the Canadian Institutes of Health Research. The other investigators and Dr. Lackland reported no relevant disclosures.

The Food and Drug Administration has approved the Amplatzer Amulet left atrial appendage occluder (Abbott) to treat people with nonvalvular atrial fibrillation who are at increased risk for stroke and systemic embolism.

The Amulet and its competitor, Boston Scientific’s Watchman, are minimally invasive devices used to close off the left atrial appendage (LAA), an area where blood clots tend to form in people with atrial fibrillation.

Amulet uses dual-seal technology to completely and immediately seal the LAA, the company says, whereas the other minimally invasive solution uses a single component to seal the LAA that requires blood-thinning drugs to heal and additional patient monitoring. The Amulet also has the widest range of occluder sizes on the market and is recapturable and repositionable to ensure optimal placement.

“As the world’s population continues to age, we’re seeing a surge in atrial fibrillation cases, and with that comes increased risk of stroke. The approval of Abbott’s Amulet device provides physicians with a treatment option that reduces the risk of stroke and eliminates the need for blood-thinning medication immediately after the procedure, which is incredibly valuable given the bleeding risks associated with these medicines,” Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute at HCA Midwest Health, Overland Park, Kan., and principal investigator for the study that led to FDA approval, said in a news release from Abbott.

The FDA approval is supported by findings from the global Amulet IDE trial, a head-to-head comparison of the Amulet and Watchman devices in 1,878 participants with nonvalvular atrial fibrillation. The results will be presented virtually on Aug. 30 at the 2021 annual congress of the European Society of Cardiology.

The Amplatzer Amulet received CE Mark designation in 2013 and is approved for use in more than 80 countries, including in Australia, Canada, and European countries.

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

The Food and Drug Administration has approved the Amplatzer Amulet left atrial appendage occluder (Abbott) to treat people with nonvalvular atrial fibrillation who are at increased risk for stroke and systemic embolism.

The Amulet and its competitor, Boston Scientific’s Watchman, are minimally invasive devices used to close off the left atrial appendage (LAA), an area where blood clots tend to form in people with atrial fibrillation.

Amulet uses dual-seal technology to completely and immediately seal the LAA, the company says, whereas the other minimally invasive solution uses a single component to seal the LAA that requires blood-thinning drugs to heal and additional patient monitoring. The Amulet also has the widest range of occluder sizes on the market and is recapturable and repositionable to ensure optimal placement.

“As the world’s population continues to age, we’re seeing a surge in atrial fibrillation cases, and with that comes increased risk of stroke. The approval of Abbott’s Amulet device provides physicians with a treatment option that reduces the risk of stroke and eliminates the need for blood-thinning medication immediately after the procedure, which is incredibly valuable given the bleeding risks associated with these medicines,” Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute at HCA Midwest Health, Overland Park, Kan., and principal investigator for the study that led to FDA approval, said in a news release from Abbott.

The FDA approval is supported by findings from the global Amulet IDE trial, a head-to-head comparison of the Amulet and Watchman devices in 1,878 participants with nonvalvular atrial fibrillation. The results will be presented virtually on Aug. 30 at the 2021 annual congress of the European Society of Cardiology.

The Amplatzer Amulet received CE Mark designation in 2013 and is approved for use in more than 80 countries, including in Australia, Canada, and European countries.

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

The Food and Drug Administration has approved the Amplatzer Amulet left atrial appendage occluder (Abbott) to treat people with nonvalvular atrial fibrillation who are at increased risk for stroke and systemic embolism.

The Amulet and its competitor, Boston Scientific’s Watchman, are minimally invasive devices used to close off the left atrial appendage (LAA), an area where blood clots tend to form in people with atrial fibrillation.

Amulet uses dual-seal technology to completely and immediately seal the LAA, the company says, whereas the other minimally invasive solution uses a single component to seal the LAA that requires blood-thinning drugs to heal and additional patient monitoring. The Amulet also has the widest range of occluder sizes on the market and is recapturable and repositionable to ensure optimal placement.

“As the world’s population continues to age, we’re seeing a surge in atrial fibrillation cases, and with that comes increased risk of stroke. The approval of Abbott’s Amulet device provides physicians with a treatment option that reduces the risk of stroke and eliminates the need for blood-thinning medication immediately after the procedure, which is incredibly valuable given the bleeding risks associated with these medicines,” Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute at HCA Midwest Health, Overland Park, Kan., and principal investigator for the study that led to FDA approval, said in a news release from Abbott.

The FDA approval is supported by findings from the global Amulet IDE trial, a head-to-head comparison of the Amulet and Watchman devices in 1,878 participants with nonvalvular atrial fibrillation. The results will be presented virtually on Aug. 30 at the 2021 annual congress of the European Society of Cardiology.

The Amplatzer Amulet received CE Mark designation in 2013 and is approved for use in more than 80 countries, including in Australia, Canada, and European countries.

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

In a large study of community-based stroke survivors in Canada, researchers found those meeting guideline-recommended levels of physical activity had a significantly lower risk for death from any cause, with a greater than 50% reduction in risk.

Lead study author Raed A. Joundi, MD, DPhil, of the University of Calgary (Alta.), said he expected results to show exercise was beneficial, but was surprised by the magnitude of the association between physical activity and lower mortality risk.

The impact of physical activity also differed significantly by age; those younger than 75 had a 79% reduction in mortality risk, compared with 32% in those age 75 and older.

“This is even after adjusting for factors such heart disease, respiratory conditions, smoking, and other functional limitations,” said Dr. Joundi.

The study was published online Aug. 11 in the journal Neurology.

For this analysis, the researchers used data on a cohort of people across Canada (excluding the province of Quebec) over 3-9 years. The 895 patients with prior stroke averaged 72 years of age, while the 97,805 in the control group had an average age of 63.

Weekly physical activity averages were evaluated using the self-reporting Canadian Community Health Survey, which was linked with administrative databases to evaluate the association of physical activity with long-term risk for mortality among stroke survivors, compared with controls.

Physical activity was measured in metabolic equivalents (METs); meeting minimum physical activity guidelines was defined as 10 MET-hours/week.

During the study period, more stroke patients than controls died (24.7% vs. 5.7%). However, those who met the physical activity guideline recommendations of 10 MET-hours/week had a lower mortality, both in the stroke survivor group (14.6% vs. 33.2%; adjusted hazard ratio, 0.46; 95% confidence interval, 0.29-0.73) and among control participants (3.6% vs. 7.9%; aHR 0.69; 95% CI, 0.62-0.76).  

The largest absolute and relative reduction in mortality was among stroke respondents younger than 75 (10.5% vs. 29%; aHR, 0.21; 95% CI, 0.10-0.43), the researchers note.

There was a significant interaction with age for the stroke patients but not the control group.

“The greatest reduction in mortality was seen between 0 and 10 METs per week … so the main point is that something is better than nothing,” said Dr. Joundi.
 

Exercise guidelines for the future

Although current guidelines recommend physical activity in stroke survivors, investigators noted that these are largely based on studies in the general population. Therefore, the aim of this research was to get a better understanding of the role of physical activity in the health of stroke survivors in the community, which could ultimately be used to design improved public health campaigns and physical activity interventions.

Given that this is a large study of stroke survivors in the community, Dr. Joundi hopes the results will influence future activity guidelines for those who have suffered a stroke.

“We found a log-linear relationship between physical activity and mortality such that 10 MET-hours/week was associated with large reductions in mortality with most benefit achieved by 20 MET-hours/week,” the authors concluded. “These thresholds could be considered for use in future guidelines for stroke.”

Clinical trials are underway to provide evidence for the implementation of exercise programs after stroke, they add, and offering physical activity programs to stroke survivors in the community “is an increasing priority in the U.S., Canada, and Europe.”

“People are at higher risk of death early on after a stroke but also months and years later, so if we can identify a relatively low-cost and easy intervention like physical activity to improve health and reduce the risk of death for stroke survivors it would be important,” Dr. Joundi said.
 

Key barriers

Paul George, MD, PhD, a stroke and vascular neurologist at Stanford (Calif.) University, said findings such as these further strengthen the argument that physical exercise is important after stroke.

“Because the study looked specifically at stroke patients, it can provide further guidance on physical activity recommendations that we provide to our patients following stroke,” said Dr. George, who was not associated with the study. 

Going forward, he said, more research is needed to identify specifically what is preventing stroke patients from exercising more. What is required, he said, is “future research to determine the key barriers to physical activity following stroke and methods to reduce these will also be important to increasing physical activity in stroke survivors.”

Dr. Joundi said determining how to tailor exercise recommendations to meet the wide range of capabilities of stroke survivors will be another key factor.

“Stroke survivors may have some disabilities, so we need to be able to engage them at an [exercise] level that’s possible for them,” he said.

The study did not include stroke survivors living in long-term care homes.

The study had no targeted funding. Coauthor Eric E. Smith, MD, MPH, reports royalties from UpToDate, and consulting fees from Alnylam, Biogen, and Javelin. Dr. Joundi and the other coauthors have disclosed no relevant financial relationships.

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

In a large study of community-based stroke survivors in Canada, researchers found those meeting guideline-recommended levels of physical activity had a significantly lower risk for death from any cause, with a greater than 50% reduction in risk.

Lead study author Raed A. Joundi, MD, DPhil, of the University of Calgary (Alta.), said he expected results to show exercise was beneficial, but was surprised by the magnitude of the association between physical activity and lower mortality risk.

The impact of physical activity also differed significantly by age; those younger than 75 had a 79% reduction in mortality risk, compared with 32% in those age 75 and older.

“This is even after adjusting for factors such heart disease, respiratory conditions, smoking, and other functional limitations,” said Dr. Joundi.

The study was published online Aug. 11 in the journal Neurology.

For this analysis, the researchers used data on a cohort of people across Canada (excluding the province of Quebec) over 3-9 years. The 895 patients with prior stroke averaged 72 years of age, while the 97,805 in the control group had an average age of 63.

Weekly physical activity averages were evaluated using the self-reporting Canadian Community Health Survey, which was linked with administrative databases to evaluate the association of physical activity with long-term risk for mortality among stroke survivors, compared with controls.

Physical activity was measured in metabolic equivalents (METs); meeting minimum physical activity guidelines was defined as 10 MET-hours/week.

During the study period, more stroke patients than controls died (24.7% vs. 5.7%). However, those who met the physical activity guideline recommendations of 10 MET-hours/week had a lower mortality, both in the stroke survivor group (14.6% vs. 33.2%; adjusted hazard ratio, 0.46; 95% confidence interval, 0.29-0.73) and among control participants (3.6% vs. 7.9%; aHR 0.69; 95% CI, 0.62-0.76).  

The largest absolute and relative reduction in mortality was among stroke respondents younger than 75 (10.5% vs. 29%; aHR, 0.21; 95% CI, 0.10-0.43), the researchers note.

There was a significant interaction with age for the stroke patients but not the control group.

“The greatest reduction in mortality was seen between 0 and 10 METs per week … so the main point is that something is better than nothing,” said Dr. Joundi.
 

Exercise guidelines for the future

Although current guidelines recommend physical activity in stroke survivors, investigators noted that these are largely based on studies in the general population. Therefore, the aim of this research was to get a better understanding of the role of physical activity in the health of stroke survivors in the community, which could ultimately be used to design improved public health campaigns and physical activity interventions.

Given that this is a large study of stroke survivors in the community, Dr. Joundi hopes the results will influence future activity guidelines for those who have suffered a stroke.

“We found a log-linear relationship between physical activity and mortality such that 10 MET-hours/week was associated with large reductions in mortality with most benefit achieved by 20 MET-hours/week,” the authors concluded. “These thresholds could be considered for use in future guidelines for stroke.”

Clinical trials are underway to provide evidence for the implementation of exercise programs after stroke, they add, and offering physical activity programs to stroke survivors in the community “is an increasing priority in the U.S., Canada, and Europe.”

“People are at higher risk of death early on after a stroke but also months and years later, so if we can identify a relatively low-cost and easy intervention like physical activity to improve health and reduce the risk of death for stroke survivors it would be important,” Dr. Joundi said.
 

Key barriers

Paul George, MD, PhD, a stroke and vascular neurologist at Stanford (Calif.) University, said findings such as these further strengthen the argument that physical exercise is important after stroke.

“Because the study looked specifically at stroke patients, it can provide further guidance on physical activity recommendations that we provide to our patients following stroke,” said Dr. George, who was not associated with the study. 

Going forward, he said, more research is needed to identify specifically what is preventing stroke patients from exercising more. What is required, he said, is “future research to determine the key barriers to physical activity following stroke and methods to reduce these will also be important to increasing physical activity in stroke survivors.”

Dr. Joundi said determining how to tailor exercise recommendations to meet the wide range of capabilities of stroke survivors will be another key factor.

“Stroke survivors may have some disabilities, so we need to be able to engage them at an [exercise] level that’s possible for them,” he said.

The study did not include stroke survivors living in long-term care homes.

The study had no targeted funding. Coauthor Eric E. Smith, MD, MPH, reports royalties from UpToDate, and consulting fees from Alnylam, Biogen, and Javelin. Dr. Joundi and the other coauthors have disclosed no relevant financial relationships.

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

In a large study of community-based stroke survivors in Canada, researchers found those meeting guideline-recommended levels of physical activity had a significantly lower risk for death from any cause, with a greater than 50% reduction in risk.

Lead study author Raed A. Joundi, MD, DPhil, of the University of Calgary (Alta.), said he expected results to show exercise was beneficial, but was surprised by the magnitude of the association between physical activity and lower mortality risk.

The impact of physical activity also differed significantly by age; those younger than 75 had a 79% reduction in mortality risk, compared with 32% in those age 75 and older.

“This is even after adjusting for factors such heart disease, respiratory conditions, smoking, and other functional limitations,” said Dr. Joundi.

The study was published online Aug. 11 in the journal Neurology.

For this analysis, the researchers used data on a cohort of people across Canada (excluding the province of Quebec) over 3-9 years. The 895 patients with prior stroke averaged 72 years of age, while the 97,805 in the control group had an average age of 63.

Weekly physical activity averages were evaluated using the self-reporting Canadian Community Health Survey, which was linked with administrative databases to evaluate the association of physical activity with long-term risk for mortality among stroke survivors, compared with controls.

Physical activity was measured in metabolic equivalents (METs); meeting minimum physical activity guidelines was defined as 10 MET-hours/week.

During the study period, more stroke patients than controls died (24.7% vs. 5.7%). However, those who met the physical activity guideline recommendations of 10 MET-hours/week had a lower mortality, both in the stroke survivor group (14.6% vs. 33.2%; adjusted hazard ratio, 0.46; 95% confidence interval, 0.29-0.73) and among control participants (3.6% vs. 7.9%; aHR 0.69; 95% CI, 0.62-0.76).  

The largest absolute and relative reduction in mortality was among stroke respondents younger than 75 (10.5% vs. 29%; aHR, 0.21; 95% CI, 0.10-0.43), the researchers note.

There was a significant interaction with age for the stroke patients but not the control group.

“The greatest reduction in mortality was seen between 0 and 10 METs per week … so the main point is that something is better than nothing,” said Dr. Joundi.
 

Exercise guidelines for the future

Although current guidelines recommend physical activity in stroke survivors, investigators noted that these are largely based on studies in the general population. Therefore, the aim of this research was to get a better understanding of the role of physical activity in the health of stroke survivors in the community, which could ultimately be used to design improved public health campaigns and physical activity interventions.

Given that this is a large study of stroke survivors in the community, Dr. Joundi hopes the results will influence future activity guidelines for those who have suffered a stroke.

“We found a log-linear relationship between physical activity and mortality such that 10 MET-hours/week was associated with large reductions in mortality with most benefit achieved by 20 MET-hours/week,” the authors concluded. “These thresholds could be considered for use in future guidelines for stroke.”

Clinical trials are underway to provide evidence for the implementation of exercise programs after stroke, they add, and offering physical activity programs to stroke survivors in the community “is an increasing priority in the U.S., Canada, and Europe.”

“People are at higher risk of death early on after a stroke but also months and years later, so if we can identify a relatively low-cost and easy intervention like physical activity to improve health and reduce the risk of death for stroke survivors it would be important,” Dr. Joundi said.
 

Key barriers

Paul George, MD, PhD, a stroke and vascular neurologist at Stanford (Calif.) University, said findings such as these further strengthen the argument that physical exercise is important after stroke.

“Because the study looked specifically at stroke patients, it can provide further guidance on physical activity recommendations that we provide to our patients following stroke,” said Dr. George, who was not associated with the study. 

Going forward, he said, more research is needed to identify specifically what is preventing stroke patients from exercising more. What is required, he said, is “future research to determine the key barriers to physical activity following stroke and methods to reduce these will also be important to increasing physical activity in stroke survivors.”

Dr. Joundi said determining how to tailor exercise recommendations to meet the wide range of capabilities of stroke survivors will be another key factor.

“Stroke survivors may have some disabilities, so we need to be able to engage them at an [exercise] level that’s possible for them,” he said.

The study did not include stroke survivors living in long-term care homes.

The study had no targeted funding. Coauthor Eric E. Smith, MD, MPH, reports royalties from UpToDate, and consulting fees from Alnylam, Biogen, and Javelin. Dr. Joundi and the other coauthors have disclosed no relevant financial relationships.

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

Short-term, 7-day prophylactic regimens are superior to longer-term strategies for preventing seizures following spontaneous intracerebral hemorrhage (sICH), new research shows.

Investigators created a model that simulated common clinical scenarios to compare four antiseizure drug strategies – conservative, moderate, aggressive, and risk-guided. They used the 2HELPS2B score as a risk stratification tool to guide clinical decisions.

The investigators found that the short-term, early-seizure prophylaxis strategies “dominated” long-term therapy under most clinical scenarios, underscoring the importance of early discontinuation of antiseizure drug therapy.

“The main message here was that strategies that involved long-term antiseizure drug prescription (moderate and aggressive) fail to provide better outcomes in most clinical scenarios, when compared with strategies using short-term prophylaxis (conservative and risk-guided),” senior investigator Lidia M.V.R. Moura, MD, MPH, assistant professor of neurology, Harvard Medical School, Boston, said in an interview.

The study was published online July 26 in JAMA Neurology.
 

Common complication

“Acute asymptomatic seizures [early seizures ≤7 days after stroke] are a common complication of sICH,” the authors noted.

Potential safety concerns have prompted recommendations against the use of antiseizure medications for primary prophylaxis. However, approximately 40% of U.S. patients with sICH do receive prophylactic levetiracetam before seizure development. For these patients, the duration of prophylaxis varies widely.

“Because seizure risk is a key determinant of which patient groups might benefit most from different prophylaxis strategies, validated tools for predicting early ... and late ... seizure risks could aid physicians in treatment decisions. However, no clinical trials or prospective studies have evaluated the net benefit of various strategies after sICH,” the investigators noted.

“Our patients who were survivors of an intracerebral hemorrhage motivated us to conduct the study,” said Dr. Moura, who is also director of the MGH NeuroValue Laboratory. “Some would come to the clinic with a long list of medications; some of them were taking antiseizure drugs for many years, but they never had a documented seizure.” These patients did not know why they had been taking an antiseizure drug for so long.

“In these conversations, we noted so much variability in indications and variability in patient access to specialty care to make treatment decisions. We noted that the evidence behind our current guidelines on seizure management was limited,” she added.

Dr. Moura and colleagues were “committed to improve outcome for people with neurological conditions by leveraging research methods that can help guide providers and systems, especially when data from clinical trials is lacking,” so they “decided to compare different strategies head to head using available data and generate evidence that could be used in situations with many trade-offs in risks and benefits.”

To investigate, the researchers used a simulation model and decision analysis to compare four treatment strategies on the basis of type of therapy (primary vs. secondary prophylaxis), timing of event (early vs. late seizures), and duration of therapy (1-week [short-term] versus indefinite [long-term] therapy).

These four strategies were as follows:

• Conservative: short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late seizure
• Moderate: long-term secondary early-seizure prophylaxis or late-seizure therapy
• Aggressive: long-term primary prophylaxis
• Risk-guided: short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2b score, 0), short-term primary prophylaxis among patients at higher risk (2HELPS2B score ≥1), and long-term secondary therapy for late seizure

The decision tree’s outcome measure was the number of expected quality-adjusted life-years.

Primary prophylaxis was defined as “treatment initiated immediately on hospital admission.” Secondary prophylaxis was defined as “treatment started after a seizure” and was subdivided into secondary early-seizure prophylaxis, defined as treatment started after a seizure occurring in the first 7 days after the stroke, or secondary late-seizure therapy, defined as treatment started or restarted after a seizure occurring after the first poststroke week.
 

Incorporate early-risk stratification tool

The researchers created four common clinical scenarios and then applied the decision-making model to each. They found that the preferred strategies differed, depending on the particular scenario.

‘Potential fallacies’

Commenting on the study, José Biller, MD, professor and chairman, department of neurology, Loyola University Chicago, Maywood, Ill., called it a “well-written and intriguing contribution [to the field], with potential fallacies.”

The bottom line, he said, is that only a randomized, long-term, prospective, multicenter, high-quality study with larger cohorts can prove or disprove the investigators’ assumption.

The authors acknowledged that a limitation of the study was the use of published literature to obtain data to estimate model parameters and that they did not account for other possible factors that might modify some parameter estimates.

Nevertheless, Dr. Moura said the findings have important practical implications because they “highlight the importance of discontinuing antiseizure medications that were started during a hospitalization for sICH in patients that only had an early seizure.”

It is “of great importance for all providers to reassess the indication of antiseizure medications. Those drugs are not free of risks and can impact the patient’s health and quality of life,” she added.

The study was supported by grants from the National Institutes of Health. Dr. Moura reported receiving funding from the Centers for Disease Control and Prevention, the NIH, and the Epilepsy Foundation of America (Epilepsy Learning Healthcare System) as the director of the data coordinating center. Dr. Biller is the editor-in-chief of the Journal of Stroke and Cerebrovascular Diseases and a section editor of UpToDate.

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

Short-term, 7-day prophylactic regimens are superior to longer-term strategies for preventing seizures following spontaneous intracerebral hemorrhage (sICH), new research shows.

Investigators created a model that simulated common clinical scenarios to compare four antiseizure drug strategies – conservative, moderate, aggressive, and risk-guided. They used the 2HELPS2B score as a risk stratification tool to guide clinical decisions.

The investigators found that the short-term, early-seizure prophylaxis strategies “dominated” long-term therapy under most clinical scenarios, underscoring the importance of early discontinuation of antiseizure drug therapy.

“The main message here was that strategies that involved long-term antiseizure drug prescription (moderate and aggressive) fail to provide better outcomes in most clinical scenarios, when compared with strategies using short-term prophylaxis (conservative and risk-guided),” senior investigator Lidia M.V.R. Moura, MD, MPH, assistant professor of neurology, Harvard Medical School, Boston, said in an interview.

The study was published online July 26 in JAMA Neurology.
 

Common complication

“Acute asymptomatic seizures [early seizures ≤7 days after stroke] are a common complication of sICH,” the authors noted.

Potential safety concerns have prompted recommendations against the use of antiseizure medications for primary prophylaxis. However, approximately 40% of U.S. patients with sICH do receive prophylactic levetiracetam before seizure development. For these patients, the duration of prophylaxis varies widely.

“Because seizure risk is a key determinant of which patient groups might benefit most from different prophylaxis strategies, validated tools for predicting early ... and late ... seizure risks could aid physicians in treatment decisions. However, no clinical trials or prospective studies have evaluated the net benefit of various strategies after sICH,” the investigators noted.

“Our patients who were survivors of an intracerebral hemorrhage motivated us to conduct the study,” said Dr. Moura, who is also director of the MGH NeuroValue Laboratory. “Some would come to the clinic with a long list of medications; some of them were taking antiseizure drugs for many years, but they never had a documented seizure.” These patients did not know why they had been taking an antiseizure drug for so long.

“In these conversations, we noted so much variability in indications and variability in patient access to specialty care to make treatment decisions. We noted that the evidence behind our current guidelines on seizure management was limited,” she added.

Dr. Moura and colleagues were “committed to improve outcome for people with neurological conditions by leveraging research methods that can help guide providers and systems, especially when data from clinical trials is lacking,” so they “decided to compare different strategies head to head using available data and generate evidence that could be used in situations with many trade-offs in risks and benefits.”

To investigate, the researchers used a simulation model and decision analysis to compare four treatment strategies on the basis of type of therapy (primary vs. secondary prophylaxis), timing of event (early vs. late seizures), and duration of therapy (1-week [short-term] versus indefinite [long-term] therapy).

These four strategies were as follows:

• Conservative: short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late seizure
• Moderate: long-term secondary early-seizure prophylaxis or late-seizure therapy
• Aggressive: long-term primary prophylaxis
• Risk-guided: short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2b score, 0), short-term primary prophylaxis among patients at higher risk (2HELPS2B score ≥1), and long-term secondary therapy for late seizure

The decision tree’s outcome measure was the number of expected quality-adjusted life-years.

Primary prophylaxis was defined as “treatment initiated immediately on hospital admission.” Secondary prophylaxis was defined as “treatment started after a seizure” and was subdivided into secondary early-seizure prophylaxis, defined as treatment started after a seizure occurring in the first 7 days after the stroke, or secondary late-seizure therapy, defined as treatment started or restarted after a seizure occurring after the first poststroke week.
 

Incorporate early-risk stratification tool

The researchers created four common clinical scenarios and then applied the decision-making model to each. They found that the preferred strategies differed, depending on the particular scenario.

‘Potential fallacies’

Commenting on the study, José Biller, MD, professor and chairman, department of neurology, Loyola University Chicago, Maywood, Ill., called it a “well-written and intriguing contribution [to the field], with potential fallacies.”

The bottom line, he said, is that only a randomized, long-term, prospective, multicenter, high-quality study with larger cohorts can prove or disprove the investigators’ assumption.

The authors acknowledged that a limitation of the study was the use of published literature to obtain data to estimate model parameters and that they did not account for other possible factors that might modify some parameter estimates.

Nevertheless, Dr. Moura said the findings have important practical implications because they “highlight the importance of discontinuing antiseizure medications that were started during a hospitalization for sICH in patients that only had an early seizure.”

It is “of great importance for all providers to reassess the indication of antiseizure medications. Those drugs are not free of risks and can impact the patient’s health and quality of life,” she added.

The study was supported by grants from the National Institutes of Health. Dr. Moura reported receiving funding from the Centers for Disease Control and Prevention, the NIH, and the Epilepsy Foundation of America (Epilepsy Learning Healthcare System) as the director of the data coordinating center. Dr. Biller is the editor-in-chief of the Journal of Stroke and Cerebrovascular Diseases and a section editor of UpToDate.

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

Short-term, 7-day prophylactic regimens are superior to longer-term strategies for preventing seizures following spontaneous intracerebral hemorrhage (sICH), new research shows.

Investigators created a model that simulated common clinical scenarios to compare four antiseizure drug strategies – conservative, moderate, aggressive, and risk-guided. They used the 2HELPS2B score as a risk stratification tool to guide clinical decisions.

The investigators found that the short-term, early-seizure prophylaxis strategies “dominated” long-term therapy under most clinical scenarios, underscoring the importance of early discontinuation of antiseizure drug therapy.

“The main message here was that strategies that involved long-term antiseizure drug prescription (moderate and aggressive) fail to provide better outcomes in most clinical scenarios, when compared with strategies using short-term prophylaxis (conservative and risk-guided),” senior investigator Lidia M.V.R. Moura, MD, MPH, assistant professor of neurology, Harvard Medical School, Boston, said in an interview.

The study was published online July 26 in JAMA Neurology.
 

Common complication

“Acute asymptomatic seizures [early seizures ≤7 days after stroke] are a common complication of sICH,” the authors noted.

Potential safety concerns have prompted recommendations against the use of antiseizure medications for primary prophylaxis. However, approximately 40% of U.S. patients with sICH do receive prophylactic levetiracetam before seizure development. For these patients, the duration of prophylaxis varies widely.

“Because seizure risk is a key determinant of which patient groups might benefit most from different prophylaxis strategies, validated tools for predicting early ... and late ... seizure risks could aid physicians in treatment decisions. However, no clinical trials or prospective studies have evaluated the net benefit of various strategies after sICH,” the investigators noted.

“Our patients who were survivors of an intracerebral hemorrhage motivated us to conduct the study,” said Dr. Moura, who is also director of the MGH NeuroValue Laboratory. “Some would come to the clinic with a long list of medications; some of them were taking antiseizure drugs for many years, but they never had a documented seizure.” These patients did not know why they had been taking an antiseizure drug for so long.

“In these conversations, we noted so much variability in indications and variability in patient access to specialty care to make treatment decisions. We noted that the evidence behind our current guidelines on seizure management was limited,” she added.

Dr. Moura and colleagues were “committed to improve outcome for people with neurological conditions by leveraging research methods that can help guide providers and systems, especially when data from clinical trials is lacking,” so they “decided to compare different strategies head to head using available data and generate evidence that could be used in situations with many trade-offs in risks and benefits.”

To investigate, the researchers used a simulation model and decision analysis to compare four treatment strategies on the basis of type of therapy (primary vs. secondary prophylaxis), timing of event (early vs. late seizures), and duration of therapy (1-week [short-term] versus indefinite [long-term] therapy).

These four strategies were as follows:

• Conservative: short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late seizure
• Moderate: long-term secondary early-seizure prophylaxis or late-seizure therapy
• Aggressive: long-term primary prophylaxis
• Risk-guided: short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2b score, 0), short-term primary prophylaxis among patients at higher risk (2HELPS2B score ≥1), and long-term secondary therapy for late seizure

The decision tree’s outcome measure was the number of expected quality-adjusted life-years.

Primary prophylaxis was defined as “treatment initiated immediately on hospital admission.” Secondary prophylaxis was defined as “treatment started after a seizure” and was subdivided into secondary early-seizure prophylaxis, defined as treatment started after a seizure occurring in the first 7 days after the stroke, or secondary late-seizure therapy, defined as treatment started or restarted after a seizure occurring after the first poststroke week.
 

Incorporate early-risk stratification tool

The researchers created four common clinical scenarios and then applied the decision-making model to each. They found that the preferred strategies differed, depending on the particular scenario.

‘Potential fallacies’

Commenting on the study, José Biller, MD, professor and chairman, department of neurology, Loyola University Chicago, Maywood, Ill., called it a “well-written and intriguing contribution [to the field], with potential fallacies.”

The bottom line, he said, is that only a randomized, long-term, prospective, multicenter, high-quality study with larger cohorts can prove or disprove the investigators’ assumption.

The authors acknowledged that a limitation of the study was the use of published literature to obtain data to estimate model parameters and that they did not account for other possible factors that might modify some parameter estimates.

Nevertheless, Dr. Moura said the findings have important practical implications because they “highlight the importance of discontinuing antiseizure medications that were started during a hospitalization for sICH in patients that only had an early seizure.”

It is “of great importance for all providers to reassess the indication of antiseizure medications. Those drugs are not free of risks and can impact the patient’s health and quality of life,” she added.

The study was supported by grants from the National Institutes of Health. Dr. Moura reported receiving funding from the Centers for Disease Control and Prevention, the NIH, and the Epilepsy Foundation of America (Epilepsy Learning Healthcare System) as the director of the data coordinating center. Dr. Biller is the editor-in-chief of the Journal of Stroke and Cerebrovascular Diseases and a section editor of UpToDate.

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

Having a mobile interventional stroke team (MIST) travel to treat stroke patients soon after stroke onset may improve patient outcomes, according to a new study. A retrospective analysis of a pilot program in New York found that patients who were treated on the ground by the MIST team rather than transferred to a specialized stroke center received faster care and were almost twice as likely to be functionally independent 3 months later.

“The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes,” wrote lead author Jacob Morey, a doctoral Candidate at Icahn School of Medicine at Mount Sinai in New York and coauthors in the paper. Prior to this study, “the effect of the MIST model stratified by time of presentation” had yet to be studied.

The findings were published online on Aug. 5 in Stroke.
 

MIST model versus drip-and-ship

The researchers analyzed 226 patients who underwent endovascular thrombectomy between January 2017 and February 2020 at four hospitals in the Mount Sinai health system using the NYC MIST Trial and a stroke database. At baseline, all patients were functionally independent as assessed by the modified Rankin Scale (mRS, score of 0-2). 106 patients were treated by a MIST team – staffed by a neurointerventionalist, a fellow or physician assistant, and radiologic technologist – that traveled to the patient’s location. A total of 120 patients were transferred to a comprehensive stroke center (CSC) or a hospital with endovascular thrombectomy expertise. The analysis was stratified based on whether the patient presented in the early time window (≤ 6 hours) or late time window (> 6 hours).

Patients treated in the early time window were significantly more likely to be mobile and able to perform daily tasks (mRS ≤ 2) 90 days after the procedure in the MIST group (54%), compared with the transferred group (28%, P < 0.01). Outcomes did not differ significantly between groups in the late time window (35% vs. 41%, P = 0.77).

Similarly, early-time-window patients in the MIST group were more likely to have higher functionality at discharge, compared with transferred patients, based on the on the National Institutes of Health Stroke Scale (median score of 5.0 vs. 12.0, P < 0.01). There was no significant difference between groups treated in the late time window (median score of 5.0 vs. 11.0, P = 0.11).

“Ischemic strokes often progress rapidly and can cause severe damage because brain tissue dies quickly without oxygen, resulting in serious long-term disabilities or death,“ said Johanna Fifi, MD, of Icahn School of Medicine, said in a statement to the American Heart Association. “Assessing and treating stroke patients in the early window means that a greater number of fast-progressing strokes are identified and treated.”

Time is brain

Endovascular thrombectomy is a time-sensitive surgical procedure to remove large blood clots in acute ischemic stroke that has “historically been limited to comprehensive stroke centers,” the authors wrote in their paper. It is considered the standard of care in ischemic strokes, which make up 90% of all strokes. “Less than 50% of Americans have direct access to endovascular thrombectomy, the others must be transferred to a thrombectomy-capable hospital for treatment, often losing over 2 hours of time to treatment,” said Dr. Fifi. “Every minute is precious in treating stroke, and getting to a center that offers thrombectomy is very important. The MIST model would address this by providing faster access to this potentially life-saving, disability-reducing procedure.”

Access to timely endovascular thrombectomy is gradually improving as “more institutions and cities have implemented the [MIST] model.” Dr. Fifi said.

“This study stresses the importance of ‘time is brain,’ especially for patients in the early time window. Although the study is limited by the observational, retrospective design and was performed at a single integrated center, the findings are provocative,” said Louise McCullough, MD, of the University of Texas Health Science Center at Houston said in a statement to the American Heart Association. “The use of a MIST model highlights the potential benefit of early and urgent treatment for patients with large-vessel stroke. Stroke systems of care need to take advantage of any opportunity to treat patients early, wherever they are.”

The study was partly funded by a Stryker Foundation grant.

Having a mobile interventional stroke team (MIST) travel to treat stroke patients soon after stroke onset may improve patient outcomes, according to a new study. A retrospective analysis of a pilot program in New York found that patients who were treated on the ground by the MIST team rather than transferred to a specialized stroke center received faster care and were almost twice as likely to be functionally independent 3 months later.

“The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes,” wrote lead author Jacob Morey, a doctoral Candidate at Icahn School of Medicine at Mount Sinai in New York and coauthors in the paper. Prior to this study, “the effect of the MIST model stratified by time of presentation” had yet to be studied.

The findings were published online on Aug. 5 in Stroke.
 

MIST model versus drip-and-ship

The researchers analyzed 226 patients who underwent endovascular thrombectomy between January 2017 and February 2020 at four hospitals in the Mount Sinai health system using the NYC MIST Trial and a stroke database. At baseline, all patients were functionally independent as assessed by the modified Rankin Scale (mRS, score of 0-2). 106 patients were treated by a MIST team – staffed by a neurointerventionalist, a fellow or physician assistant, and radiologic technologist – that traveled to the patient’s location. A total of 120 patients were transferred to a comprehensive stroke center (CSC) or a hospital with endovascular thrombectomy expertise. The analysis was stratified based on whether the patient presented in the early time window (≤ 6 hours) or late time window (> 6 hours).

Patients treated in the early time window were significantly more likely to be mobile and able to perform daily tasks (mRS ≤ 2) 90 days after the procedure in the MIST group (54%), compared with the transferred group (28%, P < 0.01). Outcomes did not differ significantly between groups in the late time window (35% vs. 41%, P = 0.77).

Similarly, early-time-window patients in the MIST group were more likely to have higher functionality at discharge, compared with transferred patients, based on the on the National Institutes of Health Stroke Scale (median score of 5.0 vs. 12.0, P < 0.01). There was no significant difference between groups treated in the late time window (median score of 5.0 vs. 11.0, P = 0.11).

“Ischemic strokes often progress rapidly and can cause severe damage because brain tissue dies quickly without oxygen, resulting in serious long-term disabilities or death,“ said Johanna Fifi, MD, of Icahn School of Medicine, said in a statement to the American Heart Association. “Assessing and treating stroke patients in the early window means that a greater number of fast-progressing strokes are identified and treated.”

Time is brain

Endovascular thrombectomy is a time-sensitive surgical procedure to remove large blood clots in acute ischemic stroke that has “historically been limited to comprehensive stroke centers,” the authors wrote in their paper. It is considered the standard of care in ischemic strokes, which make up 90% of all strokes. “Less than 50% of Americans have direct access to endovascular thrombectomy, the others must be transferred to a thrombectomy-capable hospital for treatment, often losing over 2 hours of time to treatment,” said Dr. Fifi. “Every minute is precious in treating stroke, and getting to a center that offers thrombectomy is very important. The MIST model would address this by providing faster access to this potentially life-saving, disability-reducing procedure.”

Access to timely endovascular thrombectomy is gradually improving as “more institutions and cities have implemented the [MIST] model.” Dr. Fifi said.

“This study stresses the importance of ‘time is brain,’ especially for patients in the early time window. Although the study is limited by the observational, retrospective design and was performed at a single integrated center, the findings are provocative,” said Louise McCullough, MD, of the University of Texas Health Science Center at Houston said in a statement to the American Heart Association. “The use of a MIST model highlights the potential benefit of early and urgent treatment for patients with large-vessel stroke. Stroke systems of care need to take advantage of any opportunity to treat patients early, wherever they are.”

The study was partly funded by a Stryker Foundation grant.

Having a mobile interventional stroke team (MIST) travel to treat stroke patients soon after stroke onset may improve patient outcomes, according to a new study. A retrospective analysis of a pilot program in New York found that patients who were treated on the ground by the MIST team rather than transferred to a specialized stroke center received faster care and were almost twice as likely to be functionally independent 3 months later.

“The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes,” wrote lead author Jacob Morey, a doctoral Candidate at Icahn School of Medicine at Mount Sinai in New York and coauthors in the paper. Prior to this study, “the effect of the MIST model stratified by time of presentation” had yet to be studied.

The findings were published online on Aug. 5 in Stroke.
 

MIST model versus drip-and-ship

The researchers analyzed 226 patients who underwent endovascular thrombectomy between January 2017 and February 2020 at four hospitals in the Mount Sinai health system using the NYC MIST Trial and a stroke database. At baseline, all patients were functionally independent as assessed by the modified Rankin Scale (mRS, score of 0-2). 106 patients were treated by a MIST team – staffed by a neurointerventionalist, a fellow or physician assistant, and radiologic technologist – that traveled to the patient’s location. A total of 120 patients were transferred to a comprehensive stroke center (CSC) or a hospital with endovascular thrombectomy expertise. The analysis was stratified based on whether the patient presented in the early time window (≤ 6 hours) or late time window (> 6 hours).

Patients treated in the early time window were significantly more likely to be mobile and able to perform daily tasks (mRS ≤ 2) 90 days after the procedure in the MIST group (54%), compared with the transferred group (28%, P < 0.01). Outcomes did not differ significantly between groups in the late time window (35% vs. 41%, P = 0.77).

Similarly, early-time-window patients in the MIST group were more likely to have higher functionality at discharge, compared with transferred patients, based on the on the National Institutes of Health Stroke Scale (median score of 5.0 vs. 12.0, P < 0.01). There was no significant difference between groups treated in the late time window (median score of 5.0 vs. 11.0, P = 0.11).

“Ischemic strokes often progress rapidly and can cause severe damage because brain tissue dies quickly without oxygen, resulting in serious long-term disabilities or death,“ said Johanna Fifi, MD, of Icahn School of Medicine, said in a statement to the American Heart Association. “Assessing and treating stroke patients in the early window means that a greater number of fast-progressing strokes are identified and treated.”

Time is brain

Endovascular thrombectomy is a time-sensitive surgical procedure to remove large blood clots in acute ischemic stroke that has “historically been limited to comprehensive stroke centers,” the authors wrote in their paper. It is considered the standard of care in ischemic strokes, which make up 90% of all strokes. “Less than 50% of Americans have direct access to endovascular thrombectomy, the others must be transferred to a thrombectomy-capable hospital for treatment, often losing over 2 hours of time to treatment,” said Dr. Fifi. “Every minute is precious in treating stroke, and getting to a center that offers thrombectomy is very important. The MIST model would address this by providing faster access to this potentially life-saving, disability-reducing procedure.”

Access to timely endovascular thrombectomy is gradually improving as “more institutions and cities have implemented the [MIST] model.” Dr. Fifi said.

“This study stresses the importance of ‘time is brain,’ especially for patients in the early time window. Although the study is limited by the observational, retrospective design and was performed at a single integrated center, the findings are provocative,” said Louise McCullough, MD, of the University of Texas Health Science Center at Houston said in a statement to the American Heart Association. “The use of a MIST model highlights the potential benefit of early and urgent treatment for patients with large-vessel stroke. Stroke systems of care need to take advantage of any opportunity to treat patients early, wherever they are.”

The study was partly funded by a Stryker Foundation grant.