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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.

Another trial has added to the movement toward shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

MDedge News

In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events, and was associated with a lower incidence of major or clinically relevant bleeding.

The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on Aug. 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk,” Dr. Valgimigli said. “But this has never been prospectively tested until now.”

He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included “all-comer” high-bleeding-risk patients with no selection based on ischemic risk.

M. Alexander Otto, MDedge News

The trial was very well received by commentators at the ESC Hot Line presentation.

Chair of the session, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, described the trial as “practice-changing.”

And Robert Byrne, MD, Mater Private Hospital, Dublin, added: “This is a standout trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding.”

The MASTER DAPT study involved 4,579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).

The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.

Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.

Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% confidence interval, –1.80 to 1.33 percentage points; P < .001 for noninferiority).

Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).

Reduction in bleeding driven by BARC-2

Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).

“This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35,” Dr. Valgimigli said.

The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs. 6.8%).

During the discussion, Dr. Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.

Dr. Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group receiving 3-6 months of DAPT rather than a year or more in previous studies. “Having said that, BARC-2 bleeding is not a trivial event,” he added.
 

Can results be applied to other stents?

Dr. Byrne also questioned whether the results can be applied to patients receiving other types of stents – not just Ultimaster, which is not available everywhere. Dr. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, “I would be scared to assume these results are reproducible with other stents.”

But Dr. Mehran challenged this view, saying, “I’m not so sure about that. I think we can probably extrapolate.”

In an interview, Dr. Mehran added: “I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants.  

“These results show that, although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events,” she concluded.

In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, N.C., pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.

But he concluded that: “The findings of Dr. Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI.”

In an interview, Dr. Ohman pointed out that the Ultimaster stent is not available in the United States. “We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn’t have thought so, but it is hard to say for sure.

“All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming U.S. PCI guidelines should put all the studies together and come up with recommendations on different patient groups,” he concluded.  

Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. “This is such an important group. It is difficult to interpret the results without this data,” Dr. Ohman noted.  Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting.

The MASTER DAPT trial was supported by Terumo. Dr. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and AstraZeneca. Dr. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, XyloCor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbents, Neurocrine, and Paradigm, outside the submitted work.

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

Another trial has added to the movement toward shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

MDedge News

In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events, and was associated with a lower incidence of major or clinically relevant bleeding.

The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on Aug. 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk,” Dr. Valgimigli said. “But this has never been prospectively tested until now.”

He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included “all-comer” high-bleeding-risk patients with no selection based on ischemic risk.

M. Alexander Otto, MDedge News

The trial was very well received by commentators at the ESC Hot Line presentation.

Chair of the session, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, described the trial as “practice-changing.”

And Robert Byrne, MD, Mater Private Hospital, Dublin, added: “This is a standout trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding.”

The MASTER DAPT study involved 4,579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).

The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.

Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.

Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% confidence interval, –1.80 to 1.33 percentage points; P < .001 for noninferiority).

Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).

Reduction in bleeding driven by BARC-2

Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).

“This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35,” Dr. Valgimigli said.

The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs. 6.8%).

During the discussion, Dr. Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.

Dr. Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group receiving 3-6 months of DAPT rather than a year or more in previous studies. “Having said that, BARC-2 bleeding is not a trivial event,” he added.
 

Can results be applied to other stents?

Dr. Byrne also questioned whether the results can be applied to patients receiving other types of stents – not just Ultimaster, which is not available everywhere. Dr. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, “I would be scared to assume these results are reproducible with other stents.”

But Dr. Mehran challenged this view, saying, “I’m not so sure about that. I think we can probably extrapolate.”

In an interview, Dr. Mehran added: “I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants.  

“These results show that, although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events,” she concluded.

In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, N.C., pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.

But he concluded that: “The findings of Dr. Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI.”

In an interview, Dr. Ohman pointed out that the Ultimaster stent is not available in the United States. “We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn’t have thought so, but it is hard to say for sure.

“All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming U.S. PCI guidelines should put all the studies together and come up with recommendations on different patient groups,” he concluded.  

Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. “This is such an important group. It is difficult to interpret the results without this data,” Dr. Ohman noted.  Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting.

The MASTER DAPT trial was supported by Terumo. Dr. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and AstraZeneca. Dr. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, XyloCor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbents, Neurocrine, and Paradigm, outside the submitted work.

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

Another trial has added to the movement toward shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

MDedge News

In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events, and was associated with a lower incidence of major or clinically relevant bleeding.

The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on Aug. 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk,” Dr. Valgimigli said. “But this has never been prospectively tested until now.”

He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included “all-comer” high-bleeding-risk patients with no selection based on ischemic risk.

M. Alexander Otto, MDedge News

The trial was very well received by commentators at the ESC Hot Line presentation.

Chair of the session, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, described the trial as “practice-changing.”

And Robert Byrne, MD, Mater Private Hospital, Dublin, added: “This is a standout trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding.”

The MASTER DAPT study involved 4,579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).

The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.

Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.

Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% confidence interval, –1.80 to 1.33 percentage points; P < .001 for noninferiority).

Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).

Reduction in bleeding driven by BARC-2

Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).

“This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35,” Dr. Valgimigli said.

The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs. 6.8%).

During the discussion, Dr. Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.

Dr. Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group receiving 3-6 months of DAPT rather than a year or more in previous studies. “Having said that, BARC-2 bleeding is not a trivial event,” he added.
 

Can results be applied to other stents?

Dr. Byrne also questioned whether the results can be applied to patients receiving other types of stents – not just Ultimaster, which is not available everywhere. Dr. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, “I would be scared to assume these results are reproducible with other stents.”

But Dr. Mehran challenged this view, saying, “I’m not so sure about that. I think we can probably extrapolate.”

In an interview, Dr. Mehran added: “I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants.  

“These results show that, although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events,” she concluded.

In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, N.C., pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.

But he concluded that: “The findings of Dr. Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI.”

In an interview, Dr. Ohman pointed out that the Ultimaster stent is not available in the United States. “We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn’t have thought so, but it is hard to say for sure.

“All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming U.S. PCI guidelines should put all the studies together and come up with recommendations on different patient groups,” he concluded.  

Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. “This is such an important group. It is difficult to interpret the results without this data,” Dr. Ohman noted.  Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting.

The MASTER DAPT trial was supported by Terumo. Dr. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and AstraZeneca. Dr. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, XyloCor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbents, Neurocrine, and Paradigm, outside the submitted work.

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

In patients with coronary artery disease scheduled for a percutaneous intervention (PCI), fractional flow reserve (FFR) assessment at the time of angiography significantly improves outcome, but it has no apparent value as a routine study in all CAD patients, according to the randomized RIPCORD 2 trial.

When compared to angiography alone in an all comer-strategy, the addition of FFR did not significantly change management or lower costs, but it was associated with a longer time for diagnostic assessment and more complications, Nicholas P. Curzen, BM, PhD, reported at the annual congress of the European Society of Cardiology.

As a tool for evaluating stenotic lesions in diseased vessels, FFR, also known as pressure wire assessment, allows interventionalists to target those vessels that induce ischemia without unnecessarily treating vessels with lesions that are hemodynamically nonsignificant. It is guideline recommended for patients with scheduled PCI on the basis of several randomized trials, including the landmark FAME trial.

“The results of these trials were spectacular. The clinical outcomes were significantly better in the FFR group despite less stents being placed and fewer vessels being stented. And there was significantly less resource utilization in the FFR group,” said Dr. Curzen, professor of interventional cardiology, University of Southampton, England.
 

Hypothesis: All-comers benefit from FFR

This prompted the new trial, called RIPCORD 2. The hypothesis was that systematic FFR early in the diagnosis of CAD would reduce resource utilization and improve quality of life relative to angiography alone. Both were addressed as primary endpoints. A reduction in clinical events at 12 months was a secondary endpoint.

The 1,136 participants, all scheduled for angiographic evaluation for stable angina or non-ST elevated myocardial infarction (NSTEMI), were randomized at 17 participating centers in the United Kingdom. All underwent angiography, but the experimental arm also underwent FFR for all arteries of a size suitable for revascularization.

Resource utilization evaluated through hospital costs at 12 months was somewhat higher in the FFR group, but the difference was not significant (P =.137). There was also no significant difference (P = 0.88) between the groups in quality of life, which was measured with EQ-5D-5L, an instrument for expressing five dimensions of health on a visual analog scale.
 

No impact from FFR on clinical events

Furthermore, there was no difference in the rate of clinical events, whether measured by a composite endpoint of major adverse cardiac events (MACE) (P = .64) or by the components of death, stroke, myocardial infarction, and unplanned revascularization, according to Dr. Curzen.

Finally, FFR did not appear to influence subsequent management. When the intervention and control groups were compared, the proportions triaged to optimal medical therapy, optimal medical therapy plus PCI, or optimal medical therapy plus bypass grafting did not differ significantly.  

Given the lack of significant differences for FFR plus angiography relative to angiography alone for any clinically relevant outcome, the addition of FFR provides "no overall advantage" in this all comer study population, Dr. Curzen concluded.

However, FFR was associated with some relative disadvantages. These included significantly longer mean procedure times (69 vs. 42.4 minutes; P < .001), significantly greater mean use of contrast (206 vs. 146.3 mL; P < .001), and a significantly higher mean radiation dose (6608.7 vs. 5029.7 cGY/cm²; P < .001). There were 10 complications (1.8%) associated with FFR.

RIPCORD 1 results provided study rationale

In the previously published nonrandomized RIPCORD 1 study, interventionalists were asked to develop a management plan on the basis of angiography alone in 200 patients with stable chest pain. When these interventionalists were then provided with FFR results, the new information resulted in a change of management plan in 36% of cases.

According to Dr. Curzen, it was this study that raised all-comer FFR as a “logical and clinically plausible question.” RIPCORD 2 provided the answer.

While he is now conducting an evaluation of a subgroup of RIPCORD 2 patients with more severe disease, “it appears that the atheroma burden on angiography is adequate” to make an appropriate management determination in most or all cases.

The invited discussant for this study, Robert Byrne, MD, BCh, PhD, director of cardiology, Mater Private Hospital, Dublin, pointed out that more angiography-alone patients in RIPCORD 2 required additional evaluation to develop a management strategy (14.7% vs. 1.8%), but he agreed that FFR offered “no reasonable benefit” in the relatively low-risk patients who were enrolled.
 

Results do not alter FFR indications

However, he emphasized that the lack of an advantage in this trial should in no way diminish the evidence of benefit for selective FFR use as currently recommended in guidelines. This was echoed strongly in remarks by two other interventionalists who served on the same panel after the RIPCORD 2 results were presented.

“I want to make sure that our audience does not walk away thinking that FFR is useless. This is not what was shown,” said Roxana Mehran, MD, director of interventional cardiovascular research at Icahn School of Medicine at Mount Sinai, New York. She emphasized that this was a study that found no value in a low-risk, all-comer population and is not relevant to the populations where it now has an indication.

Marco Roffi, MD, director of the interventional cardiology unit, Geneva University Hospitals, made the same point.

“These results do not take away the value of FFR in a more selected population [than that enrolled in RIPCORD 2],” Dr. Roffi said. He did not rule out the potential for benefit from adding FFR to angiography even in early disease assessment if a benefit can be demonstrated in a higher-risk population.

Dr. Curzen reports financial relationships with Abbott, Beckman Coulter, HeartFlow, and Boston Scientific, which provided funding for RIPCORD 2. Dr. Byrne reported financial relationships with the trial sponsor as well as Abbott, Biosensors, and Biotronik. Dr. Mehran reports financial relationships with more than 15 medical product companies including the sponsor of this trial. Dr. Roffi reports no relevant financial disclosures.

In patients with coronary artery disease scheduled for a percutaneous intervention (PCI), fractional flow reserve (FFR) assessment at the time of angiography significantly improves outcome, but it has no apparent value as a routine study in all CAD patients, according to the randomized RIPCORD 2 trial.

When compared to angiography alone in an all comer-strategy, the addition of FFR did not significantly change management or lower costs, but it was associated with a longer time for diagnostic assessment and more complications, Nicholas P. Curzen, BM, PhD, reported at the annual congress of the European Society of Cardiology.

As a tool for evaluating stenotic lesions in diseased vessels, FFR, also known as pressure wire assessment, allows interventionalists to target those vessels that induce ischemia without unnecessarily treating vessels with lesions that are hemodynamically nonsignificant. It is guideline recommended for patients with scheduled PCI on the basis of several randomized trials, including the landmark FAME trial.

“The results of these trials were spectacular. The clinical outcomes were significantly better in the FFR group despite less stents being placed and fewer vessels being stented. And there was significantly less resource utilization in the FFR group,” said Dr. Curzen, professor of interventional cardiology, University of Southampton, England.
 

Hypothesis: All-comers benefit from FFR

This prompted the new trial, called RIPCORD 2. The hypothesis was that systematic FFR early in the diagnosis of CAD would reduce resource utilization and improve quality of life relative to angiography alone. Both were addressed as primary endpoints. A reduction in clinical events at 12 months was a secondary endpoint.

The 1,136 participants, all scheduled for angiographic evaluation for stable angina or non-ST elevated myocardial infarction (NSTEMI), were randomized at 17 participating centers in the United Kingdom. All underwent angiography, but the experimental arm also underwent FFR for all arteries of a size suitable for revascularization.

Resource utilization evaluated through hospital costs at 12 months was somewhat higher in the FFR group, but the difference was not significant (P =.137). There was also no significant difference (P = 0.88) between the groups in quality of life, which was measured with EQ-5D-5L, an instrument for expressing five dimensions of health on a visual analog scale.
 

No impact from FFR on clinical events

Furthermore, there was no difference in the rate of clinical events, whether measured by a composite endpoint of major adverse cardiac events (MACE) (P = .64) or by the components of death, stroke, myocardial infarction, and unplanned revascularization, according to Dr. Curzen.

Finally, FFR did not appear to influence subsequent management. When the intervention and control groups were compared, the proportions triaged to optimal medical therapy, optimal medical therapy plus PCI, or optimal medical therapy plus bypass grafting did not differ significantly.  

Given the lack of significant differences for FFR plus angiography relative to angiography alone for any clinically relevant outcome, the addition of FFR provides "no overall advantage" in this all comer study population, Dr. Curzen concluded.

However, FFR was associated with some relative disadvantages. These included significantly longer mean procedure times (69 vs. 42.4 minutes; P < .001), significantly greater mean use of contrast (206 vs. 146.3 mL; P < .001), and a significantly higher mean radiation dose (6608.7 vs. 5029.7 cGY/cm²; P < .001). There were 10 complications (1.8%) associated with FFR.

RIPCORD 1 results provided study rationale

In the previously published nonrandomized RIPCORD 1 study, interventionalists were asked to develop a management plan on the basis of angiography alone in 200 patients with stable chest pain. When these interventionalists were then provided with FFR results, the new information resulted in a change of management plan in 36% of cases.

According to Dr. Curzen, it was this study that raised all-comer FFR as a “logical and clinically plausible question.” RIPCORD 2 provided the answer.

While he is now conducting an evaluation of a subgroup of RIPCORD 2 patients with more severe disease, “it appears that the atheroma burden on angiography is adequate” to make an appropriate management determination in most or all cases.

The invited discussant for this study, Robert Byrne, MD, BCh, PhD, director of cardiology, Mater Private Hospital, Dublin, pointed out that more angiography-alone patients in RIPCORD 2 required additional evaluation to develop a management strategy (14.7% vs. 1.8%), but he agreed that FFR offered “no reasonable benefit” in the relatively low-risk patients who were enrolled.
 

Results do not alter FFR indications

However, he emphasized that the lack of an advantage in this trial should in no way diminish the evidence of benefit for selective FFR use as currently recommended in guidelines. This was echoed strongly in remarks by two other interventionalists who served on the same panel after the RIPCORD 2 results were presented.

“I want to make sure that our audience does not walk away thinking that FFR is useless. This is not what was shown,” said Roxana Mehran, MD, director of interventional cardiovascular research at Icahn School of Medicine at Mount Sinai, New York. She emphasized that this was a study that found no value in a low-risk, all-comer population and is not relevant to the populations where it now has an indication.

Marco Roffi, MD, director of the interventional cardiology unit, Geneva University Hospitals, made the same point.

“These results do not take away the value of FFR in a more selected population [than that enrolled in RIPCORD 2],” Dr. Roffi said. He did not rule out the potential for benefit from adding FFR to angiography even in early disease assessment if a benefit can be demonstrated in a higher-risk population.

Dr. Curzen reports financial relationships with Abbott, Beckman Coulter, HeartFlow, and Boston Scientific, which provided funding for RIPCORD 2. Dr. Byrne reported financial relationships with the trial sponsor as well as Abbott, Biosensors, and Biotronik. Dr. Mehran reports financial relationships with more than 15 medical product companies including the sponsor of this trial. Dr. Roffi reports no relevant financial disclosures.

In patients with coronary artery disease scheduled for a percutaneous intervention (PCI), fractional flow reserve (FFR) assessment at the time of angiography significantly improves outcome, but it has no apparent value as a routine study in all CAD patients, according to the randomized RIPCORD 2 trial.

When compared to angiography alone in an all comer-strategy, the addition of FFR did not significantly change management or lower costs, but it was associated with a longer time for diagnostic assessment and more complications, Nicholas P. Curzen, BM, PhD, reported at the annual congress of the European Society of Cardiology.

As a tool for evaluating stenotic lesions in diseased vessels, FFR, also known as pressure wire assessment, allows interventionalists to target those vessels that induce ischemia without unnecessarily treating vessels with lesions that are hemodynamically nonsignificant. It is guideline recommended for patients with scheduled PCI on the basis of several randomized trials, including the landmark FAME trial.

“The results of these trials were spectacular. The clinical outcomes were significantly better in the FFR group despite less stents being placed and fewer vessels being stented. And there was significantly less resource utilization in the FFR group,” said Dr. Curzen, professor of interventional cardiology, University of Southampton, England.
 

Hypothesis: All-comers benefit from FFR

This prompted the new trial, called RIPCORD 2. The hypothesis was that systematic FFR early in the diagnosis of CAD would reduce resource utilization and improve quality of life relative to angiography alone. Both were addressed as primary endpoints. A reduction in clinical events at 12 months was a secondary endpoint.

The 1,136 participants, all scheduled for angiographic evaluation for stable angina or non-ST elevated myocardial infarction (NSTEMI), were randomized at 17 participating centers in the United Kingdom. All underwent angiography, but the experimental arm also underwent FFR for all arteries of a size suitable for revascularization.

Resource utilization evaluated through hospital costs at 12 months was somewhat higher in the FFR group, but the difference was not significant (P =.137). There was also no significant difference (P = 0.88) between the groups in quality of life, which was measured with EQ-5D-5L, an instrument for expressing five dimensions of health on a visual analog scale.
 

No impact from FFR on clinical events

Furthermore, there was no difference in the rate of clinical events, whether measured by a composite endpoint of major adverse cardiac events (MACE) (P = .64) or by the components of death, stroke, myocardial infarction, and unplanned revascularization, according to Dr. Curzen.

Finally, FFR did not appear to influence subsequent management. When the intervention and control groups were compared, the proportions triaged to optimal medical therapy, optimal medical therapy plus PCI, or optimal medical therapy plus bypass grafting did not differ significantly.  

Given the lack of significant differences for FFR plus angiography relative to angiography alone for any clinically relevant outcome, the addition of FFR provides "no overall advantage" in this all comer study population, Dr. Curzen concluded.

However, FFR was associated with some relative disadvantages. These included significantly longer mean procedure times (69 vs. 42.4 minutes; P < .001), significantly greater mean use of contrast (206 vs. 146.3 mL; P < .001), and a significantly higher mean radiation dose (6608.7 vs. 5029.7 cGY/cm²; P < .001). There were 10 complications (1.8%) associated with FFR.

RIPCORD 1 results provided study rationale

In the previously published nonrandomized RIPCORD 1 study, interventionalists were asked to develop a management plan on the basis of angiography alone in 200 patients with stable chest pain. When these interventionalists were then provided with FFR results, the new information resulted in a change of management plan in 36% of cases.

According to Dr. Curzen, it was this study that raised all-comer FFR as a “logical and clinically plausible question.” RIPCORD 2 provided the answer.

While he is now conducting an evaluation of a subgroup of RIPCORD 2 patients with more severe disease, “it appears that the atheroma burden on angiography is adequate” to make an appropriate management determination in most or all cases.

The invited discussant for this study, Robert Byrne, MD, BCh, PhD, director of cardiology, Mater Private Hospital, Dublin, pointed out that more angiography-alone patients in RIPCORD 2 required additional evaluation to develop a management strategy (14.7% vs. 1.8%), but he agreed that FFR offered “no reasonable benefit” in the relatively low-risk patients who were enrolled.
 

Results do not alter FFR indications

However, he emphasized that the lack of an advantage in this trial should in no way diminish the evidence of benefit for selective FFR use as currently recommended in guidelines. This was echoed strongly in remarks by two other interventionalists who served on the same panel after the RIPCORD 2 results were presented.

“I want to make sure that our audience does not walk away thinking that FFR is useless. This is not what was shown,” said Roxana Mehran, MD, director of interventional cardiovascular research at Icahn School of Medicine at Mount Sinai, New York. She emphasized that this was a study that found no value in a low-risk, all-comer population and is not relevant to the populations where it now has an indication.

Marco Roffi, MD, director of the interventional cardiology unit, Geneva University Hospitals, made the same point.

“These results do not take away the value of FFR in a more selected population [than that enrolled in RIPCORD 2],” Dr. Roffi said. He did not rule out the potential for benefit from adding FFR to angiography even in early disease assessment if a benefit can be demonstrated in a higher-risk population.

Dr. Curzen reports financial relationships with Abbott, Beckman Coulter, HeartFlow, and Boston Scientific, which provided funding for RIPCORD 2. Dr. Byrne reported financial relationships with the trial sponsor as well as Abbott, Biosensors, and Biotronik. Dr. Mehran reports financial relationships with more than 15 medical product companies including the sponsor of this trial. Dr. Roffi reports no relevant financial disclosures.

Having a “high normal” serum sodium level in midlife, which reflects less than optimal fluid intake, is associated with an increased risk for left ventricular hypertrophy – a heart failure (HF) precursor – and for HF itself, in older age, a new study suggests.

Georges Lievre / Fotolia.com

Compared with middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study with normal serum sodium, those with levels of 142-146 mmol/L were more likely to have left ventricular hypertrophy or HF when they were in their 70s and 80s, independent of other risk factors.  

Natalia Dmitrieva, PhD, a research scientist at the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., presented the study findings in an e-poster on Aug. 27 at the European Society of Cardiology (ESC) Congress 2021.

“Our study suggests that maintaining good hydration can prevent or at least slow down the changes within the heart that lead to heart failure,” she said in a statement from the ESC.

It “suggests that all adults should aim for eight to ten glasses of liquid [daily] and keep salt intake low,” Dr. Dmitrieva said in an interview.

However, people should not rely completely on thirst, she cautioned, especially in middle age, when thirst sensation starts to deteriorate. And too much fluid intake can be harmful and even dangerous.

Normal serum sodium is usually defined as 135-146 mmol/L, Dr. Dmitrieva explained, and this study involved only patients in ARIC with sodium levels in this range, to try to exclude patients with genetic or water-salt balance diseases.

The findings suggest that a serum sodium level of 142-146 mmol/L, which would not be flagged as abnormal by a test lab, “can be used by clinicians as a warning sign” for a patient’s increased risk for HF, she noted.

Clinicians should explain this risk to patients and advise them to drink at least 2 L per day. However, people should not try to reduce their sodium levels by drinking more than 2 to 3 L per day, she cautioned, which can be harmful and even deadly, and they should consult their doctors.
 

Watch hydration

“An important finding of this study is that sodium values considered ‘normal’ may also be deleterious,” Jacob Joseph, MD, director, heart failure program, VA Boston Healthcare System, who was not involved with this study, said in an interview.

“These results are similar to studies we have conducted in heart failure with preserved ejection fraction,” noted Dr. Joseph, associate professor of medicine at Harvard Medical School, Boston.

Their studies showed a U-shaped relationship between serum sodium values and adverse outcomes, “indicating an ‘optimal’ range of serum sodium value that was narrower than the accepted normal laboratory value range,” he noted.

The study by Dmitrieva et al. was observational and the findings would need to be verified in a randomized controlled trial, Dr. Joseph pointed out; however, the research “supports the idea that even a high normal sodium level may indicate risk of future heart failure.

“Hence, patients should pay attention to hydration,” he continued, and “clinicians should not assume that a sodium level of 142 mmol/L is appropriate and should ensure that patients are paying attention to hydration.

“In today’s busy and stress-filled lifestyle, it is easy to forget about adequate fluid intake,” Dr. Joseph added. 
 

More than 15,000 adults followed for 25 Years

To investigate the relationship between serum sodium, hydration, and future heart failure, Dr. Dmitrieva and colleagues analyzed data from 15,792 adults in ARIC who were 44-66 years of age at study entry, with serum sodium levels from 135 to 146 mmol/L.

The participants were evaluated over five visits until they reached 70-90 years.

They were divided into four groups based on their average serum sodium concentrations at study visits one and two (conducted in the first 3 years): 135 -139.5 mmol/L, 140-141.5 mmol/L, 142-143.5 mmol/L, and 144-146 mmol/L.

The researchers determined the percentage of people in each group who developed HF and left ventricular hypertrophy at visit five (25 years after study enrollment).

Patients with higher serum sodium levels had a significantly higher risk for HF and left ventricular hypertrophy, after adjustment for other risk factors, including age, blood pressure, kidney function, blood cholesterol, blood glucose, body mass index, sex, and smoking status.

Every 1 mmol/L increase in serum sodium concentration in midlife was associated with 1.20 and 1.11 increased odds of developing left ventricular hypertrophy and HF, respectively, 25 years later.

“More studies are needed to find out what proportion of people with serum sodium 142 mmol/L and higher have this [serum sodium] level because they do not drink enough and will be able to reduce it by making sure they consistently drink 2 to 2.5 L per day,” said Dr. Dmitrieva.

“It is likely that for some people, other factors that are related to genetics or diseases affecting water-salt balance could be causing their increased serum sodium levels,” she speculated.

The study was funded by the Intramural Program of the National Heart, Lung, and Blood Institute. The authors and Dr. Joseph have no relevant financial disclosures.

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

Having a “high normal” serum sodium level in midlife, which reflects less than optimal fluid intake, is associated with an increased risk for left ventricular hypertrophy – a heart failure (HF) precursor – and for HF itself, in older age, a new study suggests.

Georges Lievre / Fotolia.com

Compared with middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study with normal serum sodium, those with levels of 142-146 mmol/L were more likely to have left ventricular hypertrophy or HF when they were in their 70s and 80s, independent of other risk factors.  

Natalia Dmitrieva, PhD, a research scientist at the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., presented the study findings in an e-poster on Aug. 27 at the European Society of Cardiology (ESC) Congress 2021.

“Our study suggests that maintaining good hydration can prevent or at least slow down the changes within the heart that lead to heart failure,” she said in a statement from the ESC.

It “suggests that all adults should aim for eight to ten glasses of liquid [daily] and keep salt intake low,” Dr. Dmitrieva said in an interview.

However, people should not rely completely on thirst, she cautioned, especially in middle age, when thirst sensation starts to deteriorate. And too much fluid intake can be harmful and even dangerous.

Normal serum sodium is usually defined as 135-146 mmol/L, Dr. Dmitrieva explained, and this study involved only patients in ARIC with sodium levels in this range, to try to exclude patients with genetic or water-salt balance diseases.

The findings suggest that a serum sodium level of 142-146 mmol/L, which would not be flagged as abnormal by a test lab, “can be used by clinicians as a warning sign” for a patient’s increased risk for HF, she noted.

Clinicians should explain this risk to patients and advise them to drink at least 2 L per day. However, people should not try to reduce their sodium levels by drinking more than 2 to 3 L per day, she cautioned, which can be harmful and even deadly, and they should consult their doctors.
 

Watch hydration

“An important finding of this study is that sodium values considered ‘normal’ may also be deleterious,” Jacob Joseph, MD, director, heart failure program, VA Boston Healthcare System, who was not involved with this study, said in an interview.

“These results are similar to studies we have conducted in heart failure with preserved ejection fraction,” noted Dr. Joseph, associate professor of medicine at Harvard Medical School, Boston.

Their studies showed a U-shaped relationship between serum sodium values and adverse outcomes, “indicating an ‘optimal’ range of serum sodium value that was narrower than the accepted normal laboratory value range,” he noted.

The study by Dmitrieva et al. was observational and the findings would need to be verified in a randomized controlled trial, Dr. Joseph pointed out; however, the research “supports the idea that even a high normal sodium level may indicate risk of future heart failure.

“Hence, patients should pay attention to hydration,” he continued, and “clinicians should not assume that a sodium level of 142 mmol/L is appropriate and should ensure that patients are paying attention to hydration.

“In today’s busy and stress-filled lifestyle, it is easy to forget about adequate fluid intake,” Dr. Joseph added. 
 

More than 15,000 adults followed for 25 Years

To investigate the relationship between serum sodium, hydration, and future heart failure, Dr. Dmitrieva and colleagues analyzed data from 15,792 adults in ARIC who were 44-66 years of age at study entry, with serum sodium levels from 135 to 146 mmol/L.

The participants were evaluated over five visits until they reached 70-90 years.

They were divided into four groups based on their average serum sodium concentrations at study visits one and two (conducted in the first 3 years): 135 -139.5 mmol/L, 140-141.5 mmol/L, 142-143.5 mmol/L, and 144-146 mmol/L.

The researchers determined the percentage of people in each group who developed HF and left ventricular hypertrophy at visit five (25 years after study enrollment).

Patients with higher serum sodium levels had a significantly higher risk for HF and left ventricular hypertrophy, after adjustment for other risk factors, including age, blood pressure, kidney function, blood cholesterol, blood glucose, body mass index, sex, and smoking status.

Every 1 mmol/L increase in serum sodium concentration in midlife was associated with 1.20 and 1.11 increased odds of developing left ventricular hypertrophy and HF, respectively, 25 years later.

“More studies are needed to find out what proportion of people with serum sodium 142 mmol/L and higher have this [serum sodium] level because they do not drink enough and will be able to reduce it by making sure they consistently drink 2 to 2.5 L per day,” said Dr. Dmitrieva.

“It is likely that for some people, other factors that are related to genetics or diseases affecting water-salt balance could be causing their increased serum sodium levels,” she speculated.

The study was funded by the Intramural Program of the National Heart, Lung, and Blood Institute. The authors and Dr. Joseph have no relevant financial disclosures.

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

Having a “high normal” serum sodium level in midlife, which reflects less than optimal fluid intake, is associated with an increased risk for left ventricular hypertrophy – a heart failure (HF) precursor – and for HF itself, in older age, a new study suggests.

Georges Lievre / Fotolia.com

Compared with middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study with normal serum sodium, those with levels of 142-146 mmol/L were more likely to have left ventricular hypertrophy or HF when they were in their 70s and 80s, independent of other risk factors.  

Natalia Dmitrieva, PhD, a research scientist at the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md., presented the study findings in an e-poster on Aug. 27 at the European Society of Cardiology (ESC) Congress 2021.

“Our study suggests that maintaining good hydration can prevent or at least slow down the changes within the heart that lead to heart failure,” she said in a statement from the ESC.

It “suggests that all adults should aim for eight to ten glasses of liquid [daily] and keep salt intake low,” Dr. Dmitrieva said in an interview.

However, people should not rely completely on thirst, she cautioned, especially in middle age, when thirst sensation starts to deteriorate. And too much fluid intake can be harmful and even dangerous.

Normal serum sodium is usually defined as 135-146 mmol/L, Dr. Dmitrieva explained, and this study involved only patients in ARIC with sodium levels in this range, to try to exclude patients with genetic or water-salt balance diseases.

The findings suggest that a serum sodium level of 142-146 mmol/L, which would not be flagged as abnormal by a test lab, “can be used by clinicians as a warning sign” for a patient’s increased risk for HF, she noted.

Clinicians should explain this risk to patients and advise them to drink at least 2 L per day. However, people should not try to reduce their sodium levels by drinking more than 2 to 3 L per day, she cautioned, which can be harmful and even deadly, and they should consult their doctors.
 

Watch hydration

“An important finding of this study is that sodium values considered ‘normal’ may also be deleterious,” Jacob Joseph, MD, director, heart failure program, VA Boston Healthcare System, who was not involved with this study, said in an interview.

“These results are similar to studies we have conducted in heart failure with preserved ejection fraction,” noted Dr. Joseph, associate professor of medicine at Harvard Medical School, Boston.

Their studies showed a U-shaped relationship between serum sodium values and adverse outcomes, “indicating an ‘optimal’ range of serum sodium value that was narrower than the accepted normal laboratory value range,” he noted.

The study by Dmitrieva et al. was observational and the findings would need to be verified in a randomized controlled trial, Dr. Joseph pointed out; however, the research “supports the idea that even a high normal sodium level may indicate risk of future heart failure.

“Hence, patients should pay attention to hydration,” he continued, and “clinicians should not assume that a sodium level of 142 mmol/L is appropriate and should ensure that patients are paying attention to hydration.

“In today’s busy and stress-filled lifestyle, it is easy to forget about adequate fluid intake,” Dr. Joseph added. 
 

More than 15,000 adults followed for 25 Years

To investigate the relationship between serum sodium, hydration, and future heart failure, Dr. Dmitrieva and colleagues analyzed data from 15,792 adults in ARIC who were 44-66 years of age at study entry, with serum sodium levels from 135 to 146 mmol/L.

The participants were evaluated over five visits until they reached 70-90 years.

They were divided into four groups based on their average serum sodium concentrations at study visits one and two (conducted in the first 3 years): 135 -139.5 mmol/L, 140-141.5 mmol/L, 142-143.5 mmol/L, and 144-146 mmol/L.

The researchers determined the percentage of people in each group who developed HF and left ventricular hypertrophy at visit five (25 years after study enrollment).

Patients with higher serum sodium levels had a significantly higher risk for HF and left ventricular hypertrophy, after adjustment for other risk factors, including age, blood pressure, kidney function, blood cholesterol, blood glucose, body mass index, sex, and smoking status.

Every 1 mmol/L increase in serum sodium concentration in midlife was associated with 1.20 and 1.11 increased odds of developing left ventricular hypertrophy and HF, respectively, 25 years later.

“More studies are needed to find out what proportion of people with serum sodium 142 mmol/L and higher have this [serum sodium] level because they do not drink enough and will be able to reduce it by making sure they consistently drink 2 to 2.5 L per day,” said Dr. Dmitrieva.

“It is likely that for some people, other factors that are related to genetics or diseases affecting water-salt balance could be causing their increased serum sodium levels,” she speculated.

The study was funded by the Intramural Program of the National Heart, Lung, and Blood Institute. The authors and Dr. Joseph have 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.

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.

When a patient has permanent atrial fibrillation (AFib) and advanced heart failure (HF), rate control therapy is an option but an “ablate-and-pace” strategy may be better at improving symptoms. The ablate-and-pace approach, compared to pharmacologic rate control, may even prolong survival in a subset of such patients when the accompanying pacemaker provides cardiac resynchronization therapy (CRT), suggests a new randomized trial.

In the APAF-CRT trial, mortality fell more than 70% over 4 years for such patients with HF and narrow QRS intervals who were assigned to ablate-and-pace – that is, CRT after creation of heart block by atrioventricular (AV) junction ablation – compared to those managed medically.

The benefit was seen regardless of left ventricular ejection fraction (LVEF) at the start of the trial and probably stemmed from “the combination of strict rate control and rate regulation achieved by AV-junction ablation together with biventricular pacing,” said Michele Brignole, MD, Istituto Auxologico Italiano, Ospedale San Luca, Milan. The CRT substitution for a standard pacemaker, he explained, is thought to “counteract” the adverse remodeling effects of apical right ventricular (RV) pacing.

Dr. Brignole delivered the remarks at a media presentation before his presentation of the APAF-CRT during the virtual annual congress of the European Society of Cardiology.

The results “support ablation-CRT as a first-line therapy in patients with permanent AFib and narrow QRS who were hospitalized for heart failure,” regardless of ejection fraction, said Dr. Brignole, lead author on the study’s same-day publication in the European Heart Journal.

“The results are not surprising. They are in line with prior studies with shorter follow-up, and they justify a relatively common practice today, to implant CRT in these patients. It has previously been shown to improve heart failure and quality of life, and is now proven to improve survival because of the longer follow-up,” Michael Glikson, MD, Shaare Zedek Medical Center, Jerusalem, said at the media briefing.

“The APAF-CRT mortality trial makes an important contribution to establishment of AV-nodal ablation with CRT as first-line therapy of resistant atrial fibrillation with heart failure, mostly in patients with reduced ejection fraction,” said Dr. Glikson, who was not part of the trial.

However, he added, “the advantage of CRT over RV pacing is still somewhat unclear in patients with normal or preserved ejection fraction,” who were relatively few in APAF-CRT and in whom RV apical pacing after AV nodal ablation has not been shown to make a big difference to ventricular function.

The new analysis covered the trial’s second phase, which featured a mortality primary endpoint, in contrast to the previously reported initial stage that followed the first 102 patients over 2 years for death, worsening HF, or HF hospitalization.

The first phase had halted enrollment before reaching its planned target of 280 patients when an interim analysis showed a significant benefit for ablate and pace. The mortality trial continued to recruit at 11 centers in Europe, reaching 133 patients, who were followed for up to 4 years, the report notes. But its enrollment had also been suspended after an interim analysis saw superiority in the ablate-and-pace arm.

APAF-CRT entered patients with severely symptomatic permanent AFib for longer than 6 months, with a QRS interval no greater than 110 ms, who had at least one HF hospitalization in the last year and were considered poor candidates for AFib ablation. Their mean age was 73 years, and almost half, 47%, were women.

They were randomly assigned to ablate-and-pace with CRT or pharmacologic rate control therapy, 63 and 70 patients, respectively. Patients in either group could be given an implantable defibrillator at physician discretion.

Patients had been followed a median of 29 months when the trial was stopped for efficacy. The hazard ratio (HR) for death from any cause, ablate-and-pace vs. rate control, was 0.26 (95% confidence interval, 0.10-0.65; P = .004), with a number needed to treat to prevent an event of 3.7. The HR was 0.40 (95% CI, 0.22-0.73; P = .002) for the secondary endpoint of death or HF hospitalization.

The new ESC guidelines on cardiac pacing and cardiac resynchronization therapy recommend “that if the ejection fraction is subnormal, they should receive a CRT as the first choice,” Dr. Glikson said. “However, for patients who are undergoing AV nodal ablation and have normal ejection fractions, we thought that RV apical pacing should be okay,” so that was the main recommendation, he said.

“I think that the APAF-CRT study does not really change this approach” because the study was small and there were few data on such patients.

APAF-CRT was an investigator-initiated independent clinical trial, sponsored by a nonprofit organization, Centro Prevenzione Malattie Cardiorespiratorie ‘Nuccia e Vittore Corbella’, Rapallo, Italy, which received an unrestricted research grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee. Dr. Brignole declared no conflicts. Disclosures for the other authors are in the report. Dr. Glikson had no disclosures.

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

When a patient has permanent atrial fibrillation (AFib) and advanced heart failure (HF), rate control therapy is an option but an “ablate-and-pace” strategy may be better at improving symptoms. The ablate-and-pace approach, compared to pharmacologic rate control, may even prolong survival in a subset of such patients when the accompanying pacemaker provides cardiac resynchronization therapy (CRT), suggests a new randomized trial.

In the APAF-CRT trial, mortality fell more than 70% over 4 years for such patients with HF and narrow QRS intervals who were assigned to ablate-and-pace – that is, CRT after creation of heart block by atrioventricular (AV) junction ablation – compared to those managed medically.

The benefit was seen regardless of left ventricular ejection fraction (LVEF) at the start of the trial and probably stemmed from “the combination of strict rate control and rate regulation achieved by AV-junction ablation together with biventricular pacing,” said Michele Brignole, MD, Istituto Auxologico Italiano, Ospedale San Luca, Milan. The CRT substitution for a standard pacemaker, he explained, is thought to “counteract” the adverse remodeling effects of apical right ventricular (RV) pacing.

Dr. Brignole delivered the remarks at a media presentation before his presentation of the APAF-CRT during the virtual annual congress of the European Society of Cardiology.

The results “support ablation-CRT as a first-line therapy in patients with permanent AFib and narrow QRS who were hospitalized for heart failure,” regardless of ejection fraction, said Dr. Brignole, lead author on the study’s same-day publication in the European Heart Journal.

“The results are not surprising. They are in line with prior studies with shorter follow-up, and they justify a relatively common practice today, to implant CRT in these patients. It has previously been shown to improve heart failure and quality of life, and is now proven to improve survival because of the longer follow-up,” Michael Glikson, MD, Shaare Zedek Medical Center, Jerusalem, said at the media briefing.

“The APAF-CRT mortality trial makes an important contribution to establishment of AV-nodal ablation with CRT as first-line therapy of resistant atrial fibrillation with heart failure, mostly in patients with reduced ejection fraction,” said Dr. Glikson, who was not part of the trial.

However, he added, “the advantage of CRT over RV pacing is still somewhat unclear in patients with normal or preserved ejection fraction,” who were relatively few in APAF-CRT and in whom RV apical pacing after AV nodal ablation has not been shown to make a big difference to ventricular function.

The new analysis covered the trial’s second phase, which featured a mortality primary endpoint, in contrast to the previously reported initial stage that followed the first 102 patients over 2 years for death, worsening HF, or HF hospitalization.

The first phase had halted enrollment before reaching its planned target of 280 patients when an interim analysis showed a significant benefit for ablate and pace. The mortality trial continued to recruit at 11 centers in Europe, reaching 133 patients, who were followed for up to 4 years, the report notes. But its enrollment had also been suspended after an interim analysis saw superiority in the ablate-and-pace arm.

APAF-CRT entered patients with severely symptomatic permanent AFib for longer than 6 months, with a QRS interval no greater than 110 ms, who had at least one HF hospitalization in the last year and were considered poor candidates for AFib ablation. Their mean age was 73 years, and almost half, 47%, were women.

They were randomly assigned to ablate-and-pace with CRT or pharmacologic rate control therapy, 63 and 70 patients, respectively. Patients in either group could be given an implantable defibrillator at physician discretion.

Patients had been followed a median of 29 months when the trial was stopped for efficacy. The hazard ratio (HR) for death from any cause, ablate-and-pace vs. rate control, was 0.26 (95% confidence interval, 0.10-0.65; P = .004), with a number needed to treat to prevent an event of 3.7. The HR was 0.40 (95% CI, 0.22-0.73; P = .002) for the secondary endpoint of death or HF hospitalization.

The new ESC guidelines on cardiac pacing and cardiac resynchronization therapy recommend “that if the ejection fraction is subnormal, they should receive a CRT as the first choice,” Dr. Glikson said. “However, for patients who are undergoing AV nodal ablation and have normal ejection fractions, we thought that RV apical pacing should be okay,” so that was the main recommendation, he said.

“I think that the APAF-CRT study does not really change this approach” because the study was small and there were few data on such patients.

APAF-CRT was an investigator-initiated independent clinical trial, sponsored by a nonprofit organization, Centro Prevenzione Malattie Cardiorespiratorie ‘Nuccia e Vittore Corbella’, Rapallo, Italy, which received an unrestricted research grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee. Dr. Brignole declared no conflicts. Disclosures for the other authors are in the report. Dr. Glikson had no disclosures.

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

When a patient has permanent atrial fibrillation (AFib) and advanced heart failure (HF), rate control therapy is an option but an “ablate-and-pace” strategy may be better at improving symptoms. The ablate-and-pace approach, compared to pharmacologic rate control, may even prolong survival in a subset of such patients when the accompanying pacemaker provides cardiac resynchronization therapy (CRT), suggests a new randomized trial.

In the APAF-CRT trial, mortality fell more than 70% over 4 years for such patients with HF and narrow QRS intervals who were assigned to ablate-and-pace – that is, CRT after creation of heart block by atrioventricular (AV) junction ablation – compared to those managed medically.

The benefit was seen regardless of left ventricular ejection fraction (LVEF) at the start of the trial and probably stemmed from “the combination of strict rate control and rate regulation achieved by AV-junction ablation together with biventricular pacing,” said Michele Brignole, MD, Istituto Auxologico Italiano, Ospedale San Luca, Milan. The CRT substitution for a standard pacemaker, he explained, is thought to “counteract” the adverse remodeling effects of apical right ventricular (RV) pacing.

Dr. Brignole delivered the remarks at a media presentation before his presentation of the APAF-CRT during the virtual annual congress of the European Society of Cardiology.

The results “support ablation-CRT as a first-line therapy in patients with permanent AFib and narrow QRS who were hospitalized for heart failure,” regardless of ejection fraction, said Dr. Brignole, lead author on the study’s same-day publication in the European Heart Journal.

“The results are not surprising. They are in line with prior studies with shorter follow-up, and they justify a relatively common practice today, to implant CRT in these patients. It has previously been shown to improve heart failure and quality of life, and is now proven to improve survival because of the longer follow-up,” Michael Glikson, MD, Shaare Zedek Medical Center, Jerusalem, said at the media briefing.

“The APAF-CRT mortality trial makes an important contribution to establishment of AV-nodal ablation with CRT as first-line therapy of resistant atrial fibrillation with heart failure, mostly in patients with reduced ejection fraction,” said Dr. Glikson, who was not part of the trial.

However, he added, “the advantage of CRT over RV pacing is still somewhat unclear in patients with normal or preserved ejection fraction,” who were relatively few in APAF-CRT and in whom RV apical pacing after AV nodal ablation has not been shown to make a big difference to ventricular function.

The new analysis covered the trial’s second phase, which featured a mortality primary endpoint, in contrast to the previously reported initial stage that followed the first 102 patients over 2 years for death, worsening HF, or HF hospitalization.

The first phase had halted enrollment before reaching its planned target of 280 patients when an interim analysis showed a significant benefit for ablate and pace. The mortality trial continued to recruit at 11 centers in Europe, reaching 133 patients, who were followed for up to 4 years, the report notes. But its enrollment had also been suspended after an interim analysis saw superiority in the ablate-and-pace arm.

APAF-CRT entered patients with severely symptomatic permanent AFib for longer than 6 months, with a QRS interval no greater than 110 ms, who had at least one HF hospitalization in the last year and were considered poor candidates for AFib ablation. Their mean age was 73 years, and almost half, 47%, were women.

They were randomly assigned to ablate-and-pace with CRT or pharmacologic rate control therapy, 63 and 70 patients, respectively. Patients in either group could be given an implantable defibrillator at physician discretion.

Patients had been followed a median of 29 months when the trial was stopped for efficacy. The hazard ratio (HR) for death from any cause, ablate-and-pace vs. rate control, was 0.26 (95% confidence interval, 0.10-0.65; P = .004), with a number needed to treat to prevent an event of 3.7. The HR was 0.40 (95% CI, 0.22-0.73; P = .002) for the secondary endpoint of death or HF hospitalization.

The new ESC guidelines on cardiac pacing and cardiac resynchronization therapy recommend “that if the ejection fraction is subnormal, they should receive a CRT as the first choice,” Dr. Glikson said. “However, for patients who are undergoing AV nodal ablation and have normal ejection fractions, we thought that RV apical pacing should be okay,” so that was the main recommendation, he said.

“I think that the APAF-CRT study does not really change this approach” because the study was small and there were few data on such patients.

APAF-CRT was an investigator-initiated independent clinical trial, sponsored by a nonprofit organization, Centro Prevenzione Malattie Cardiorespiratorie ‘Nuccia e Vittore Corbella’, Rapallo, Italy, which received an unrestricted research grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee. Dr. Brignole declared no conflicts. Disclosures for the other authors are in the report. Dr. Glikson had no disclosures.

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

New data on using the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone to treat patients with type 2 diabetes and chronic kidney disease did more than further confirm this new drug’s efficacy in these patients for slowing progression to end-stage renal disease and reducing hospitalizations for heart failure.

It also strengthened the case for clinicians to be much more proactive in collecting urine specimens from patients with type 2 diabetes (T2D) to find those with albuminuria whose kidney function has not yet dropped below 60 mL/min per 1.73 m², a population that the data show finerenone can help.

The FIDELITY prespecified meta-analysis combined data from two related pivotal trials of finerenone (Kerendia) in a total of more than 13,000 patients with T2D and chronic kidney disease (CKD). Each of these two trials, FIDELIO-DKD and FIGARO-DKD, identified patients with CKD by either of two methods, or a total of four different criteria.

In sum, the two trials enrolled patients with an estimated glomerular filtration rate (eGFR) of 25-90 mL/min per 1.73 m² and a urinary albumin-to-creatinine ratio (UACR) of 30-299, or an eGFR of 25-75 mL/min per 1.73 m² and a UACR of 300-5,000. The result was that 40% of enrolled patients had an eGFR of at least 60, levels that are considered normal, but they also had some level of albuminuria that defined them as having CKD.

The results showed that during a median follow-up of 36 months, patients with a normal eGFR and albuminuria had their combined incidence of cardiovascular disease events (cardiovascular death, MI, stroke, or hospitalization for heart failure) reduced by roughly the same amount as seen in patients with lower levels of eGFR and renal function, a finding that reimagines how clinicians need to routinely screen patients with T2D for CKD, Gerasimos Filippatos, MD, reported at the virtual annual congress of the European Society of Cardiology.

“Measuring UACR in patients with type 2 diabetes is important to identify patients who will benefit from finerenone treatment independent of their eGFR,” said Dr. Filippatos, professor of medicine at the University of Athens and director of the heart failure unit at Attikon University Hospital in Athens.

The combined FIDELITY analysis showed a significant overall cut in the combined cardiovascular disease endpoint of 14% relative to placebo, which reflected a 1.7% absolute reduction in events between the two arms during 3 years of treatment. The primary driver of this benefit was the significant drop in hospitalizations for heart failure on finerenone compared with placebo, which fell by a relative 22% and by an absolute 1.1%, Dr. Filippatos reported.

Routinely screening for albuminuria is ‘practice changing’

“This is really practice changing information for cardiologists,” said Rajiv L. Agarwal, MD, a copresenter of the FIDELITY analysis and a lead investigator of the two finerenone trials.

When cardiologists and possibly other specialists see patients with T2D, they traditionally have focused on measuring left ventricular ejection fraction and checking for other indications of heart failure. The new results from FIDELIO-DKD and FIGARO-DKD showed that finerenone treatment can prevent heart failure onset or worsening in patients with T2D with finerenone, which clinicians can accomplish by “simply measuring UACR,” as well as eGFR, and then treating patients with abnormal levels of either, explained Dr. Agarwal, a nephrologist and professor of medicine at Indiana University in Indianapolis.

“Diabetologists know that when they see patients with diabetes they need to collect a urine sample to check for albuminuria. But when some other clinicians see a patient with type 2 diabetes and a normal eGFR, they often think that the patient is okay and don’t get a urine specimen,” noted Bertram Pitt, MD, another collaborator of the finerenone trials and a heart failure specialist affiliated with the University of Michigan in Ann Arbor.

American College of Cardiology

“We need to pay more attention to UACR and albuminuria; traditionally clinicians have mostly looked at eGFR,” agreed Dipti Itchhaporia, MD, a cardiologist at the Carlton Heart and Vascular Institute of Hoag Hospital in Newport Beach, Calif. UACR “is a marker that should be shared” between endocrinologists, nephrologists, and cardiologists as they together care for patients with T2D, suggested Dr. Itchhaporia, president of the American College of Cardiology.
 

Two pivotal trials with consistent findings

The FIDELITY analysis combined data from the FIDELIO-DKD trial, reported in 2020, and from the FIGARO-DKD trial that was first reported during the current congress as well as in a simultaneous report published online.

Results from the two trials were very consistent, although the primary endpoint in FIDELIO-DKD was a composite measure of renal disease with the combined cardiovascular disease metric a secondary endpoint, while this got flipped in FIGARO-DKD which had the cardiovascular disease composite as its primary endpoint as the combined renal outcomes as a secondary endpoint.

In addition to showing a consistent, significant reduction in both combined cardiovascular disease events and in the specific endpoint of hospitalization for heart failure, the two trials also showed a consistent benefit for slowing renal disease progression, including significantly fewer patients developing end-stage kidney disease. In the combined FIDELITY analysis, treatment with finerenone cut the incidence of end-stage kidney disease by a significant 20% compared with placebo, and by an absolute reduction of 0.6%.

Another common finding was a relatively low incidence of hyperkalemia compared with what’s usually seen using a steroidal MRA, spironolactone or eplerenone. In the combined analysis treatment with finerenone produced a 14% incidence of any hyperkalemia compared with 7% among placebo-treated patients, and the rate of patients stopping their treatment because of hyperkalemia was 1.7% on finerenone and 0.6% on placebo.

“Finerenone is much better tolerated” than the steroidal MRAs in causing clinically significant hyperkalemia, noted Dr. Pitt. “There are a lot of misconceptions” about the potassium-raising potential of MRAs, and “people get frightened” by the potential. Spreading the message of finerenone’s relative safety “will take a lot of education,” he acknowledged. Routine monitoring of potassium levels is a key step to minimizing the risk for hyperkalemia when using finerenone, he added.
 

Suggested benefit from combination treatment

Another intriguing observation from FIDELITY derived from the fact that roughly 7% of enrolled patients were also on treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor at entry, and about 7% were on treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, and in both subgroups the incidence of the composite cardiovascular disease endpoint appeared to suggest additive effects of agents from either of these classes when combined with finerenone. Although the numbers of patients on combined treatment were too low to show a definitive result, “our expectation is that we will see an additive effect,” said Dr. Pitt. Ideally, patients with T2D and CKD “should be on both” an SGLT2 inhibitor and finerenone, he predicted.

SGLT2 inhibitors have now been embraced as a key treatment for patients with T2D or with heart failure with reduced ejection fraction, and the preliminary data suggest that combining these agents with finerenone can provide additional benefit, agreed Dr. Itchhaporia. Aside from the need for more evidence to prove this, there are also practical considerations of “How do we pay for all these fantastic therapies?” She expressed optimism that cost-benefit analyses will eventually show that the additive benefits justify the added cost.

Based largely on results from FIDELIO-DKD, finerenone received marketing approval from the Food and Drug Administration in July 2021 for the indication of treating patients with T2D and chronic kidney disease.

FIGARO-DKD, FIDELIO-DKD, and FIDELITY were sponsored by Bayer, the company that markets finerenone. Dr. Filippatos has received lecture fees from Bayer, and has had financial relationships with Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Agarwal received travel support from and has been a consultant to Bayer and to numerous other companies. Dr. Pitt has been a consultant to Bayer and to numerous other companies. Dr. Itchhaporia had no disclosures.

mzoler@mdedge.com

New data on using the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone to treat patients with type 2 diabetes and chronic kidney disease did more than further confirm this new drug’s efficacy in these patients for slowing progression to end-stage renal disease and reducing hospitalizations for heart failure.

It also strengthened the case for clinicians to be much more proactive in collecting urine specimens from patients with type 2 diabetes (T2D) to find those with albuminuria whose kidney function has not yet dropped below 60 mL/min per 1.73 m², a population that the data show finerenone can help.

The FIDELITY prespecified meta-analysis combined data from two related pivotal trials of finerenone (Kerendia) in a total of more than 13,000 patients with T2D and chronic kidney disease (CKD). Each of these two trials, FIDELIO-DKD and FIGARO-DKD, identified patients with CKD by either of two methods, or a total of four different criteria.

In sum, the two trials enrolled patients with an estimated glomerular filtration rate (eGFR) of 25-90 mL/min per 1.73 m² and a urinary albumin-to-creatinine ratio (UACR) of 30-299, or an eGFR of 25-75 mL/min per 1.73 m² and a UACR of 300-5,000. The result was that 40% of enrolled patients had an eGFR of at least 60, levels that are considered normal, but they also had some level of albuminuria that defined them as having CKD.

The results showed that during a median follow-up of 36 months, patients with a normal eGFR and albuminuria had their combined incidence of cardiovascular disease events (cardiovascular death, MI, stroke, or hospitalization for heart failure) reduced by roughly the same amount as seen in patients with lower levels of eGFR and renal function, a finding that reimagines how clinicians need to routinely screen patients with T2D for CKD, Gerasimos Filippatos, MD, reported at the virtual annual congress of the European Society of Cardiology.

“Measuring UACR in patients with type 2 diabetes is important to identify patients who will benefit from finerenone treatment independent of their eGFR,” said Dr. Filippatos, professor of medicine at the University of Athens and director of the heart failure unit at Attikon University Hospital in Athens.

The combined FIDELITY analysis showed a significant overall cut in the combined cardiovascular disease endpoint of 14% relative to placebo, which reflected a 1.7% absolute reduction in events between the two arms during 3 years of treatment. The primary driver of this benefit was the significant drop in hospitalizations for heart failure on finerenone compared with placebo, which fell by a relative 22% and by an absolute 1.1%, Dr. Filippatos reported.

Routinely screening for albuminuria is ‘practice changing’

“This is really practice changing information for cardiologists,” said Rajiv L. Agarwal, MD, a copresenter of the FIDELITY analysis and a lead investigator of the two finerenone trials.

When cardiologists and possibly other specialists see patients with T2D, they traditionally have focused on measuring left ventricular ejection fraction and checking for other indications of heart failure. The new results from FIDELIO-DKD and FIGARO-DKD showed that finerenone treatment can prevent heart failure onset or worsening in patients with T2D with finerenone, which clinicians can accomplish by “simply measuring UACR,” as well as eGFR, and then treating patients with abnormal levels of either, explained Dr. Agarwal, a nephrologist and professor of medicine at Indiana University in Indianapolis.

“Diabetologists know that when they see patients with diabetes they need to collect a urine sample to check for albuminuria. But when some other clinicians see a patient with type 2 diabetes and a normal eGFR, they often think that the patient is okay and don’t get a urine specimen,” noted Bertram Pitt, MD, another collaborator of the finerenone trials and a heart failure specialist affiliated with the University of Michigan in Ann Arbor.

American College of Cardiology

“We need to pay more attention to UACR and albuminuria; traditionally clinicians have mostly looked at eGFR,” agreed Dipti Itchhaporia, MD, a cardiologist at the Carlton Heart and Vascular Institute of Hoag Hospital in Newport Beach, Calif. UACR “is a marker that should be shared” between endocrinologists, nephrologists, and cardiologists as they together care for patients with T2D, suggested Dr. Itchhaporia, president of the American College of Cardiology.
 

Two pivotal trials with consistent findings

The FIDELITY analysis combined data from the FIDELIO-DKD trial, reported in 2020, and from the FIGARO-DKD trial that was first reported during the current congress as well as in a simultaneous report published online.

Results from the two trials were very consistent, although the primary endpoint in FIDELIO-DKD was a composite measure of renal disease with the combined cardiovascular disease metric a secondary endpoint, while this got flipped in FIGARO-DKD which had the cardiovascular disease composite as its primary endpoint as the combined renal outcomes as a secondary endpoint.

In addition to showing a consistent, significant reduction in both combined cardiovascular disease events and in the specific endpoint of hospitalization for heart failure, the two trials also showed a consistent benefit for slowing renal disease progression, including significantly fewer patients developing end-stage kidney disease. In the combined FIDELITY analysis, treatment with finerenone cut the incidence of end-stage kidney disease by a significant 20% compared with placebo, and by an absolute reduction of 0.6%.

Another common finding was a relatively low incidence of hyperkalemia compared with what’s usually seen using a steroidal MRA, spironolactone or eplerenone. In the combined analysis treatment with finerenone produced a 14% incidence of any hyperkalemia compared with 7% among placebo-treated patients, and the rate of patients stopping their treatment because of hyperkalemia was 1.7% on finerenone and 0.6% on placebo.

“Finerenone is much better tolerated” than the steroidal MRAs in causing clinically significant hyperkalemia, noted Dr. Pitt. “There are a lot of misconceptions” about the potassium-raising potential of MRAs, and “people get frightened” by the potential. Spreading the message of finerenone’s relative safety “will take a lot of education,” he acknowledged. Routine monitoring of potassium levels is a key step to minimizing the risk for hyperkalemia when using finerenone, he added.
 

Suggested benefit from combination treatment

Another intriguing observation from FIDELITY derived from the fact that roughly 7% of enrolled patients were also on treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor at entry, and about 7% were on treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, and in both subgroups the incidence of the composite cardiovascular disease endpoint appeared to suggest additive effects of agents from either of these classes when combined with finerenone. Although the numbers of patients on combined treatment were too low to show a definitive result, “our expectation is that we will see an additive effect,” said Dr. Pitt. Ideally, patients with T2D and CKD “should be on both” an SGLT2 inhibitor and finerenone, he predicted.

SGLT2 inhibitors have now been embraced as a key treatment for patients with T2D or with heart failure with reduced ejection fraction, and the preliminary data suggest that combining these agents with finerenone can provide additional benefit, agreed Dr. Itchhaporia. Aside from the need for more evidence to prove this, there are also practical considerations of “How do we pay for all these fantastic therapies?” She expressed optimism that cost-benefit analyses will eventually show that the additive benefits justify the added cost.

Based largely on results from FIDELIO-DKD, finerenone received marketing approval from the Food and Drug Administration in July 2021 for the indication of treating patients with T2D and chronic kidney disease.

FIGARO-DKD, FIDELIO-DKD, and FIDELITY were sponsored by Bayer, the company that markets finerenone. Dr. Filippatos has received lecture fees from Bayer, and has had financial relationships with Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Agarwal received travel support from and has been a consultant to Bayer and to numerous other companies. Dr. Pitt has been a consultant to Bayer and to numerous other companies. Dr. Itchhaporia had no disclosures.

mzoler@mdedge.com

New data on using the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone to treat patients with type 2 diabetes and chronic kidney disease did more than further confirm this new drug’s efficacy in these patients for slowing progression to end-stage renal disease and reducing hospitalizations for heart failure.

It also strengthened the case for clinicians to be much more proactive in collecting urine specimens from patients with type 2 diabetes (T2D) to find those with albuminuria whose kidney function has not yet dropped below 60 mL/min per 1.73 m², a population that the data show finerenone can help.

The FIDELITY prespecified meta-analysis combined data from two related pivotal trials of finerenone (Kerendia) in a total of more than 13,000 patients with T2D and chronic kidney disease (CKD). Each of these two trials, FIDELIO-DKD and FIGARO-DKD, identified patients with CKD by either of two methods, or a total of four different criteria.

In sum, the two trials enrolled patients with an estimated glomerular filtration rate (eGFR) of 25-90 mL/min per 1.73 m² and a urinary albumin-to-creatinine ratio (UACR) of 30-299, or an eGFR of 25-75 mL/min per 1.73 m² and a UACR of 300-5,000. The result was that 40% of enrolled patients had an eGFR of at least 60, levels that are considered normal, but they also had some level of albuminuria that defined them as having CKD.

The results showed that during a median follow-up of 36 months, patients with a normal eGFR and albuminuria had their combined incidence of cardiovascular disease events (cardiovascular death, MI, stroke, or hospitalization for heart failure) reduced by roughly the same amount as seen in patients with lower levels of eGFR and renal function, a finding that reimagines how clinicians need to routinely screen patients with T2D for CKD, Gerasimos Filippatos, MD, reported at the virtual annual congress of the European Society of Cardiology.

“Measuring UACR in patients with type 2 diabetes is important to identify patients who will benefit from finerenone treatment independent of their eGFR,” said Dr. Filippatos, professor of medicine at the University of Athens and director of the heart failure unit at Attikon University Hospital in Athens.

The combined FIDELITY analysis showed a significant overall cut in the combined cardiovascular disease endpoint of 14% relative to placebo, which reflected a 1.7% absolute reduction in events between the two arms during 3 years of treatment. The primary driver of this benefit was the significant drop in hospitalizations for heart failure on finerenone compared with placebo, which fell by a relative 22% and by an absolute 1.1%, Dr. Filippatos reported.

Routinely screening for albuminuria is ‘practice changing’

“This is really practice changing information for cardiologists,” said Rajiv L. Agarwal, MD, a copresenter of the FIDELITY analysis and a lead investigator of the two finerenone trials.

When cardiologists and possibly other specialists see patients with T2D, they traditionally have focused on measuring left ventricular ejection fraction and checking for other indications of heart failure. The new results from FIDELIO-DKD and FIGARO-DKD showed that finerenone treatment can prevent heart failure onset or worsening in patients with T2D with finerenone, which clinicians can accomplish by “simply measuring UACR,” as well as eGFR, and then treating patients with abnormal levels of either, explained Dr. Agarwal, a nephrologist and professor of medicine at Indiana University in Indianapolis.

“Diabetologists know that when they see patients with diabetes they need to collect a urine sample to check for albuminuria. But when some other clinicians see a patient with type 2 diabetes and a normal eGFR, they often think that the patient is okay and don’t get a urine specimen,” noted Bertram Pitt, MD, another collaborator of the finerenone trials and a heart failure specialist affiliated with the University of Michigan in Ann Arbor.

American College of Cardiology

“We need to pay more attention to UACR and albuminuria; traditionally clinicians have mostly looked at eGFR,” agreed Dipti Itchhaporia, MD, a cardiologist at the Carlton Heart and Vascular Institute of Hoag Hospital in Newport Beach, Calif. UACR “is a marker that should be shared” between endocrinologists, nephrologists, and cardiologists as they together care for patients with T2D, suggested Dr. Itchhaporia, president of the American College of Cardiology.
 

Two pivotal trials with consistent findings

The FIDELITY analysis combined data from the FIDELIO-DKD trial, reported in 2020, and from the FIGARO-DKD trial that was first reported during the current congress as well as in a simultaneous report published online.

Results from the two trials were very consistent, although the primary endpoint in FIDELIO-DKD was a composite measure of renal disease with the combined cardiovascular disease metric a secondary endpoint, while this got flipped in FIGARO-DKD which had the cardiovascular disease composite as its primary endpoint as the combined renal outcomes as a secondary endpoint.

In addition to showing a consistent, significant reduction in both combined cardiovascular disease events and in the specific endpoint of hospitalization for heart failure, the two trials also showed a consistent benefit for slowing renal disease progression, including significantly fewer patients developing end-stage kidney disease. In the combined FIDELITY analysis, treatment with finerenone cut the incidence of end-stage kidney disease by a significant 20% compared with placebo, and by an absolute reduction of 0.6%.

Another common finding was a relatively low incidence of hyperkalemia compared with what’s usually seen using a steroidal MRA, spironolactone or eplerenone. In the combined analysis treatment with finerenone produced a 14% incidence of any hyperkalemia compared with 7% among placebo-treated patients, and the rate of patients stopping their treatment because of hyperkalemia was 1.7% on finerenone and 0.6% on placebo.

“Finerenone is much better tolerated” than the steroidal MRAs in causing clinically significant hyperkalemia, noted Dr. Pitt. “There are a lot of misconceptions” about the potassium-raising potential of MRAs, and “people get frightened” by the potential. Spreading the message of finerenone’s relative safety “will take a lot of education,” he acknowledged. Routine monitoring of potassium levels is a key step to minimizing the risk for hyperkalemia when using finerenone, he added.
 

Suggested benefit from combination treatment

Another intriguing observation from FIDELITY derived from the fact that roughly 7% of enrolled patients were also on treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor at entry, and about 7% were on treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, and in both subgroups the incidence of the composite cardiovascular disease endpoint appeared to suggest additive effects of agents from either of these classes when combined with finerenone. Although the numbers of patients on combined treatment were too low to show a definitive result, “our expectation is that we will see an additive effect,” said Dr. Pitt. Ideally, patients with T2D and CKD “should be on both” an SGLT2 inhibitor and finerenone, he predicted.

SGLT2 inhibitors have now been embraced as a key treatment for patients with T2D or with heart failure with reduced ejection fraction, and the preliminary data suggest that combining these agents with finerenone can provide additional benefit, agreed Dr. Itchhaporia. Aside from the need for more evidence to prove this, there are also practical considerations of “How do we pay for all these fantastic therapies?” She expressed optimism that cost-benefit analyses will eventually show that the additive benefits justify the added cost.

Based largely on results from FIDELIO-DKD, finerenone received marketing approval from the Food and Drug Administration in July 2021 for the indication of treating patients with T2D and chronic kidney disease.

FIGARO-DKD, FIDELIO-DKD, and FIDELITY were sponsored by Bayer, the company that markets finerenone. Dr. Filippatos has received lecture fees from Bayer, and has had financial relationships with Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Agarwal received travel support from and has been a consultant to Bayer and to numerous other companies. Dr. Pitt has been a consultant to Bayer and to numerous other companies. Dr. Itchhaporia had no disclosures.

mzoler@mdedge.com

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

Dapagliflozin might reduce the risk for ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF), a post hoc analysis of the DAPA-HF trial suggests.

The addition of dapagliflozin to standard therapy reduced the relative risk for the primary composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death by 21%, compared with placebo (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99). The absolute risk reduction was 1.5% (5.9% vs. 7.4%).

The benefit was consistent in a competing-risks analysis that included all-cause mortality (HR, 0.80; P = .043) and across the individual components of the composite outcome, James Curtain, MD, Cardiovascular Research Centre of Glasgow, said at the annual congress of the European Society of Cardiology.

As previously reported from the main trial, treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor cut the primary endpoint of cardiovascular death or worsening heart failure by 26% among 4,744 patients with HFrEF and in New York Heart Association functional class 2-4.

Cochair of the late-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin reduced sudden cardiac deaths and related events to an extent similar to that observed for cardiovascular deaths, total mortality, and the main trial’s primary endpoint.

“So does that mean it has any particular effect on arrhythmic events or does it mean, such as a beta-blocker, for example, [it] reduces calcium transience and improves handling of calcium, or does it have an effect simply by improving heart failure?” he asked.

Dr. Curtain replied they are still trying to understand the effects of this new class of drug but that studies have shown dapagliflozin and other SGLT2 inhibitors have favorable effects on adverse cardiac remodeling, which contributes to sudden death and ventricular arrhythmia. They’ve also been shown to reduce cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over time, consistent with a reduction in myocardial wall stress. “So it could indeed be one of several mechanisms by which they may exert a beneficial cardiac effect.”

Speaking with this news organization, Dr. Curtain pointed out that the Kaplan-Meier curves for the composite outcome began to separate early on, but that the clearest separation was after 9 months, suggestive of a positive action on adverse cardiac remodeling over time.

“This would improve the patients’ heart failure situation, but also thick ventricles are a key risk factor for the occurrence of sudden death and ventricular arrhythmias,” he said. “The effects on adverse cardiac remodeling, given its plausibility in terms of our Kaplan-Meier curves, are one [mechanism] that I’d look to in the first instance, but I’m sure there are more than one actions at play.”

According to the new analysis, the primary outcome occurred in 315 (6.6%) patients; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and 8 resuscitated cardiac arrests (3%). Independent predictors of the primary outcome were higher NT-proBNP levels (odds ratio, 1.54), previous ventricular arrhythmia (OR, 1.93), previous myocardial infarction (OR, 1.42), male sex (OR, 1.53), and higher body mass index (OR, 1.03).

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

In the wake of the Centers for Disease Control and Prevention’s recommendation for a third COVID-19 mRNA vaccine dose for immunocompromised people and the Food and Drug Administration’s authorization of the third dose, the National Institute of Allergy and Infectious Diseases has begun a phase 2 trial to assess the antibody response to a booster dose of the Pfizer-BioNTech, Moderna, or Janssen vaccine in people with autoimmune disease who did not respond to their original COVID-19 vaccine regimen, according to an announcement.

The investigators of the trial, called COVID‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, also want to determine if pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine.

The trial will specifically look at the effects of mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and methotrexate (MTX), or receipt of B cell–depletion therapy such as rituximab within the past 12 months on immune response to a booster dose in people with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, or pemphigus. They have to have either no serologic response to their initial COVID-19 vaccine regimen or a suboptimal response, defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result greater than or equal to 50 U/mL.

The results of studies conducted in solid-organ transplant recipients who take immunosuppressants showed that an extra dose of vaccine could improve the immune response to the vaccine in many of the individuals, which suggests that the same approach might work in people with autoimmune disease who need treatment with immunosuppressive drugs. Improving the immune response of people with autoimmune disease to COVID-19 vaccines is important because higher rates of severe COVID-19 and death have been reported in this group of patients than in the general population, and it is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The open-label trial, conducted by the NIAID-funded Autoimmunity Centers of Excellence, aims to enroll 600 people aged 18 years and older with those conditions at 15-20 sites in the United States.

Because medications commonly taken by people with these conditions have been associated with poorer immune responses to vaccines, the trial will randomize the following two cohorts to stop or continue taking their immunosuppressive medication(s) or stop them before and after the booster according to protocol:

• Cohort 1 includes people who are taking MMF or MPA, without additional B cell–depleting medications or MTX.
• Cohort 2 includes people who are taking MTX without additional B cell–depleting medications or MMF/MPA.

A third, nonrandomized cohort consists of people who have received B cell–depletion therapy within the past 12 months regardless of whether they are also taking MMF/MPA or MTX.

Besides the cohort-specific exclusions, other rheumatic disease medications, including biologics, are allowed in the groups.

The primary outcome of the trial is the proportion of participants who have a protective antibody response at week 4. Secondary outcomes will examine various antibody responses at intervals, changes in disease activity across autoimmune diseases, adverse events, and SARS-CoV-2 infections out to 48 weeks.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021, according to the National Institutes of Health.

The trial is being led by Judith James, MD, PhD; Meggan Mackay, MD, MS; Dinesh Khanna, MBBS, MSc; and Amit Bar-Or, MD.

jevans@mdedge.com

In the wake of the Centers for Disease Control and Prevention’s recommendation for a third COVID-19 mRNA vaccine dose for immunocompromised people and the Food and Drug Administration’s authorization of the third dose, the National Institute of Allergy and Infectious Diseases has begun a phase 2 trial to assess the antibody response to a booster dose of the Pfizer-BioNTech, Moderna, or Janssen vaccine in people with autoimmune disease who did not respond to their original COVID-19 vaccine regimen, according to an announcement.

The investigators of the trial, called COVID‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, also want to determine if pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine.

The trial will specifically look at the effects of mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and methotrexate (MTX), or receipt of B cell–depletion therapy such as rituximab within the past 12 months on immune response to a booster dose in people with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, or pemphigus. They have to have either no serologic response to their initial COVID-19 vaccine regimen or a suboptimal response, defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result greater than or equal to 50 U/mL.

The results of studies conducted in solid-organ transplant recipients who take immunosuppressants showed that an extra dose of vaccine could improve the immune response to the vaccine in many of the individuals, which suggests that the same approach might work in people with autoimmune disease who need treatment with immunosuppressive drugs. Improving the immune response of people with autoimmune disease to COVID-19 vaccines is important because higher rates of severe COVID-19 and death have been reported in this group of patients than in the general population, and it is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The open-label trial, conducted by the NIAID-funded Autoimmunity Centers of Excellence, aims to enroll 600 people aged 18 years and older with those conditions at 15-20 sites in the United States.

Because medications commonly taken by people with these conditions have been associated with poorer immune responses to vaccines, the trial will randomize the following two cohorts to stop or continue taking their immunosuppressive medication(s) or stop them before and after the booster according to protocol:

• Cohort 1 includes people who are taking MMF or MPA, without additional B cell–depleting medications or MTX.
• Cohort 2 includes people who are taking MTX without additional B cell–depleting medications or MMF/MPA.

A third, nonrandomized cohort consists of people who have received B cell–depletion therapy within the past 12 months regardless of whether they are also taking MMF/MPA or MTX.

Besides the cohort-specific exclusions, other rheumatic disease medications, including biologics, are allowed in the groups.

The primary outcome of the trial is the proportion of participants who have a protective antibody response at week 4. Secondary outcomes will examine various antibody responses at intervals, changes in disease activity across autoimmune diseases, adverse events, and SARS-CoV-2 infections out to 48 weeks.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021, according to the National Institutes of Health.

The trial is being led by Judith James, MD, PhD; Meggan Mackay, MD, MS; Dinesh Khanna, MBBS, MSc; and Amit Bar-Or, MD.

jevans@mdedge.com

In the wake of the Centers for Disease Control and Prevention’s recommendation for a third COVID-19 mRNA vaccine dose for immunocompromised people and the Food and Drug Administration’s authorization of the third dose, the National Institute of Allergy and Infectious Diseases has begun a phase 2 trial to assess the antibody response to a booster dose of the Pfizer-BioNTech, Moderna, or Janssen vaccine in people with autoimmune disease who did not respond to their original COVID-19 vaccine regimen, according to an announcement.

The investigators of the trial, called COVID‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, also want to determine if pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine.

The trial will specifically look at the effects of mycophenolate mofetil (MMF) or mycophenolic acid (MPA), and methotrexate (MTX), or receipt of B cell–depletion therapy such as rituximab within the past 12 months on immune response to a booster dose in people with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, or pemphigus. They have to have either no serologic response to their initial COVID-19 vaccine regimen or a suboptimal response, defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result greater than or equal to 50 U/mL.

The results of studies conducted in solid-organ transplant recipients who take immunosuppressants showed that an extra dose of vaccine could improve the immune response to the vaccine in many of the individuals, which suggests that the same approach might work in people with autoimmune disease who need treatment with immunosuppressive drugs. Improving the immune response of people with autoimmune disease to COVID-19 vaccines is important because higher rates of severe COVID-19 and death have been reported in this group of patients than in the general population, and it is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The open-label trial, conducted by the NIAID-funded Autoimmunity Centers of Excellence, aims to enroll 600 people aged 18 years and older with those conditions at 15-20 sites in the United States.

Because medications commonly taken by people with these conditions have been associated with poorer immune responses to vaccines, the trial will randomize the following two cohorts to stop or continue taking their immunosuppressive medication(s) or stop them before and after the booster according to protocol:

• Cohort 1 includes people who are taking MMF or MPA, without additional B cell–depleting medications or MTX.
• Cohort 2 includes people who are taking MTX without additional B cell–depleting medications or MMF/MPA.

A third, nonrandomized cohort consists of people who have received B cell–depletion therapy within the past 12 months regardless of whether they are also taking MMF/MPA or MTX.

Besides the cohort-specific exclusions, other rheumatic disease medications, including biologics, are allowed in the groups.

The primary outcome of the trial is the proportion of participants who have a protective antibody response at week 4. Secondary outcomes will examine various antibody responses at intervals, changes in disease activity across autoimmune diseases, adverse events, and SARS-CoV-2 infections out to 48 weeks.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021, according to the National Institutes of Health.

The trial is being led by Judith James, MD, PhD; Meggan Mackay, MD, MS; Dinesh Khanna, MBBS, MSc; and Amit Bar-Or, MD.

jevans@mdedge.com

After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.

wildpixel/iStock/Getty Images

When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.

The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).

“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”

The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.

Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.

The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
 

ECG used to define autonomic dysfunction

In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.

The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.

After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.

The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).

Arrhythmias warn of impending complications

“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”

Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.

“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”

Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.

“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
 

Data provide insight on unaddressed risk group

SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.

An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.

“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.

Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.

After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.

wildpixel/iStock/Getty Images

When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.

The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).

“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”

The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.

Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.

The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
 

ECG used to define autonomic dysfunction

In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.

The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.

After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.

The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).

Arrhythmias warn of impending complications

“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”

Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.

“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”

Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.

“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
 

Data provide insight on unaddressed risk group

SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.

An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.

“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.

Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.

After a myocardial infarction, implantable cardiac monitors (ICMs) are sensitive for detecting serious arrhythmias in patients with cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction (LVEF), according to results of the randomized SMART-MI trial.

wildpixel/iStock/Getty Images

When remote monitoring with the ICM was compared with conventional follow-up in this group of patients, serious arrhythmic events were detected at a nearly sixfold greater rate, reported Axel Bauer, MD, at the annual congress of the European Society of Cardiology.

The study further showed that these events were closely associated with subsequent major adverse cardiac and cerebrovascular events (MACCE).

“SMART-MI is the first study to test an implantable device in high-risk MI patients with a LVEF greater than 35%,” reported Dr. Bauer, a cardiologist and director of the internal medicine clinic, University of Innsbruck (Austria). It showed that the types and frequency of arrhythmias were “comparable to those of post-MI patients with reduced LVEF.”

The ability to assess risk is potentially significant because “the majority of cardiovascular complications, including sudden death, occur in patients with only moderately reduced LVEF,” explained Dr. Bauer.

Despite the greater risk, “there are no preventive strategies so far” currently available for this group, he said.

The SMART-MI study confirms the need for treatments, confirms a method for monitoring risk, and might provide the basis for trials designed to test treatments to modify this risk, he added.
 

ECG used to define autonomic dysfunction

In the SMART MI protocol, 1,305 survivors of MI with LVEF of 36%-50% at 33 participating centers in Austria and Germany were evaluated with a 20-minute high resolution electrocardiogram. They were enrolled and randomized if they demonstrated cardiac autonomic dysfunction on at least two validated ECG biomarkers.

The 400 participants were randomized to implantation of a ICM, which transmitted daily reports to a ICM core laboratory, or to conventional follow-up.

After a median follow-up of 21 months, serious events were detected in 60 of the 201 patients in the ICM group and 12 of the 199 patients in the control group (29% vs. 6%). Serious adverse events were defined as those that would typically warrant therapy, such as prolonged atrial fibrillation (at least 6 minutes) high-degree atrioventricular block, and sustained ventricular tachycardia.

The difference in the detection rate, which was the primary endpoint, was highly significant (P < .0001), but the study was also able to confirm that these events predicted MACCE, a secondary study endpoint. In those with a serious arrhythmia, the hazard ratio for subsequent MACCE was approximately sevenfold greater relative to those without a serious arrhythmia. This was true of those in the ICM group (HR, 6.8; P < .001) and controls (HR 7.3; P < .001).

Arrhythmias warn of impending complications

“The data show that the prognostic impact of detecting a serious arrhythmia does not depend on the mode of detection,” Dr. Bauer reported. The data also confirm that “subclinical serious arrhythmia events are a warning signal for an impending complication.”

Although more interventions – including pacemakers, catheter ablations, and oral anticoagulants – were offered to patients in the experimental arm, “the study was not powered to show differences in outcomes,” and, in fact, no significant differences were observed, according to Dr. Bauer. However, the evidence that ICM is effective for detecting arrhythmias does provide a structure on which to build clinical trials.

“We now need the trials to see if ICM can change practice and improve outcomes,” said Carlos Aguiar, MD, a staff cardiologist at the Hospital Santa Cruz, Lisbon. He acknowledged that this study proves that ICM can detect serious arrhythmias in patients with moderate left ventricular dysfunction, but “we need to develop and test treatment paths.”

Dr. Aguiar considers SMART-MI an important study that “goes to the heart” of a common clinical dilemma.

“In clinical practice, we see patients with LVEF that is not that suppressed and so do not have a class I indication for ICM, but there are often features that might have you concerned and make you think it would be great if the LVEF was 35% or lower [to justify intervention],” Dr. Aguiar said.
 

Data provide insight on unaddressed risk group

SMART-MI confirms earlier evidence that post-MI patients with cardiac autonomic dysfunction are at high risk. Currently, this relative increase in risk goes “unaddressed,” according to Dr. Bauer. Although he contended that the risk itself “could be an indication for ICM in a high-risk patient group without classically defined left ventricular dysfunction,” he agreed that the ultimate value of this trial might be that it “opens a window” for a rationale to test preventive strategies.

An invited ESC discussant, Gerhard Hindricks, MD, PhD, praised the study for drawing attention to the risk of events in a subset of post-MI patients with LVEF of 35% or greater. However, he suggested that criteria other than those based on ECG might be more sensitive for selecting patients who might benefit from intervention.

“We do not know whether additional methods of establishing risk, such as imaging, might be valuable,” said Dr. Hindricks, chief of the department of arrhythmology in the Heart Institute of the University of Leipzig (Germany). He believes work in this area is needed to ensure appropriate entry criteria for interventional trials designed to modify risk in post-MI patients who do not meet the traditional definition of reduced ejection fraction.

Dr. Bauer reports financial relationships with Medtronic, which sponsored this study, as well as Bayer, Boehringer Ingelheim, Edwards, and Novartis. Dr. Aguiar reports no relevant financial conflicts.