Interventional Cardiology & Surgery

Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.

In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.

Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).

The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.

The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.

Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.

With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.

FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.

Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).

At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).

Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).

Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.

When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.

“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”

Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.

Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).

“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.

Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
 

Translating the benefits

Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.

“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.

The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.

Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”

With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.

“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”

In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”

Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.

Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”

The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.

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

Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.

In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.

Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).

The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.

The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.

Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.

With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.

FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.

Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).

At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).

Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).

Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.

When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.

“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”

Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.

Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).

“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.

Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
 

Translating the benefits

Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.

“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.

The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.

Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”

With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.

“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”

In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”

Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.

Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”

The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.

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

Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.

In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.

Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).

The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.

The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.

Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.

With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.

FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.

Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).

At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).

Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).

Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.

When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.

“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”

Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.

Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).

“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.

Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
 

Translating the benefits

Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.

“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.

The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.

Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”

With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.

“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”

In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”

Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.

Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”

The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.

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

Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.

For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.

Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.

“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.

In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.

Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.

From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
 

ARBs slow annualized aortic growth rate significantly

In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.

“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.

In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).

A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.

“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.

Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.

As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
 

Results could change treatment guidelines

Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.

“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”

As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.

Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.

On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”

While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”

Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.

Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.

Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.

For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.

Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.

“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.

In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.

Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.

From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
 

ARBs slow annualized aortic growth rate significantly

In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.

“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.

In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).

A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.

“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.

Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.

As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
 

Results could change treatment guidelines

Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.

“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”

As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.

Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.

On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”

While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”

Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.

Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.

Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.

For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.

Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.

“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.

In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.

Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.

From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
 

ARBs slow annualized aortic growth rate significantly

In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.

“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.

In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).

A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.

“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.

Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.

As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
 

Results could change treatment guidelines

Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.

“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”

As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.

Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.

On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”

While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”

Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.

Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.

New randomized trial results show no benefit in clinical outcomes from active surveillance using functional testing over usual care among high-risk patients with previous percutaneous coronary intervention (PCI).

At 2 years, there was no difference in a composite outcome of death from any cause, MI, or hospitalization for unstable angina between patients who had routine functional testing at 1 year and patients receiving standard care in the POST-PCI trial.

“Our trial does not support active surveillance with routine functional testing for follow-up strategy in high-risk patients who undergo PCI,” first author Duk-Woo Park, MD, division of cardiology, Asan Medical Center, University of Ulsan, Seoul, South Korea, said in an interview.

The researchers said their results should be interpreted in the context of previous findings from the ISCHEMIA trial that showed no difference in death or ischemic events with an initial invasive versus an initial conservative approach in patients with stable coronary artery disease and moderate to severe ischemia on stress testing.

“Both the ISCHEMIA and POST-PCI trials show the benefits of a ‘less is more’ concept (i.e., if more invasive strategies or testing are performed less frequently, it will result in better patient outcomes),” the authors wrote. Although characteristics of the patients in these trials “were quite different, a more invasive therapeutic approach (in the ISCHEMIA trial) as well as a more aggressive follow-up approach (in the POST-PCI trial) did not provide an additional treatment effect beyond a conservative strategy on the basis of guideline-directed medical therapy.”

Results were presented at the annual congress of the European Society of Cardiology and published online simultaneously in the New England Journal of Medicine.
 

‘Compelling new evidence’

In an editorial accompanying the publication, Jacqueline E. Tamis-Holland, MD, Icahn School of Medicine at Mount Sinai, Mount Sinai Morningside Hospital, New York, also agreed that this new result “builds on the findings” from the ISCHEMIA trial. “Collectively, these trials highlight the lack of benefit of routine stress testing in asymptomatic patients.”

Dr. Tamis-Holland pointed out that many of the deaths in this trial occurred before the 1-year stress test, possibly related to stent thrombosis, and therefore would not have been prevented by routine testing at 1 year. And overall, event rates were “quite low, and most likely reflect adherence to guideline recommendations” in the trial. For example, 99% of patients were receiving statins, and 74% of the procedures used intravascular imaging for the PCI procedures, “a much greater proportion of use than most centers in the United States,” she noted.

“The POST-PCI trial provides compelling new evidence for a future class III recommendation for routine surveillance testing after PCI,” Dr. Tamis-Holland concluded “Until then, we must refrain from prescribing surveillance stress testing to our patients after PCI, in the absence of other clinical signs or symptoms suggestive of stent failure.”

Commenting on the results, B. Hadley Wilson, MD, executive vice chair of the Sanger Heart & Vascular Institute/Atrium Health, clinical professor of medicine at University of North Carolina at Chapel Hill, and vice president of the American College of Cardiology, said that for decades it’s been thought that patients who had high-risk PCI needed to be followed more closely for potential future events. 

“And it actually turned out there was no difference in outcomes between the groups,” he said in an interview.

“So, I think it’s a good study – well conducted, good numbers –  that answers the question that routine functional stress testing, even for high-risk PCI patients, is not effective or cost effective or beneficial on a yearly basis,” he said. “I think it will help frame care that patients will just be followed with best medical therapy and then if they have recurrence of symptoms they would be considered for further evaluation, either with stress testing or angiography.”
 

High-risk characteristics

Current guidelines do not advocate the use of routine stress testing after revascularization, the authors wrote in their paper. “However, surveillance with the use of imaging-based stress testing may be considered in high-risk patients at 6 months after a revascularization procedure (class IIb recommendation), and routine imaging-based stress testing may be considered at 1 year after PCI and more than 5 years after CABG [coronary artery bypass graft] (class IIb recommendation).”

But in real-world clinical practice, Dr. Park said, “follow-up strategy for patients who underwent PCI or CABG is still undetermined.” Particularly, “it could be more problematic in high-risk PCI patients with high-risk anatomical or clinical characteristics. Thus, we performed this POST-PCI trial comparing routine stress testing follow-up strategy versus standard-care follow-up strategy in high-risk PCI patients.”

The researchers randomly assigned 1,706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing, including nuclear stress testing, exercise electrocardiography, or stress echocardiography at 1 year, or to standard care alone.

High-risk anatomical features included left main or bifurcation disease; restenotic or long, diffuse lesions; or bypass graft disease. High-risk clinical characteristics included diabetes mellitus, chronic kidney disease, or enzyme-positive acute coronary syndrome.

Mean age of the patients was 64.7 years; 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents.

At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval, 0.61-1.35; P = .62). There were no between-group differences in the components of the primary outcome.

Secondary endpoints included invasive coronary angiography or repeat revascularization. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, −0.01 to 5.99 percentage points), and 8.1% and 5.8% of patients, respectively, had a repeat revascularization procedure (difference, 2.23 percentage points; 95% CI, −0.22 to 4.68 percentage points).

Positive results on stress tests were more common with nuclear imaging than with exercise ECG or stress echocardiography, the authors noted. Subsequent coronary angiography and repeat revascularization were more common in patients with positive results on nuclear stress imaging and exercise ECG than in those with discordant results between nuclear imaging and exercise ECG.

POST-PCI was funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical Company. Dr. Park reported grants from the Cardiovascular Research Foundation and Daewoong Pharmaceutical Company. Dr. Tamis-Holland reported “other” funding from Pfizer  outside the submitted work. Dr. Wilson reported no relevant disclosures.

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

New randomized trial results show no benefit in clinical outcomes from active surveillance using functional testing over usual care among high-risk patients with previous percutaneous coronary intervention (PCI).

At 2 years, there was no difference in a composite outcome of death from any cause, MI, or hospitalization for unstable angina between patients who had routine functional testing at 1 year and patients receiving standard care in the POST-PCI trial.

“Our trial does not support active surveillance with routine functional testing for follow-up strategy in high-risk patients who undergo PCI,” first author Duk-Woo Park, MD, division of cardiology, Asan Medical Center, University of Ulsan, Seoul, South Korea, said in an interview.

The researchers said their results should be interpreted in the context of previous findings from the ISCHEMIA trial that showed no difference in death or ischemic events with an initial invasive versus an initial conservative approach in patients with stable coronary artery disease and moderate to severe ischemia on stress testing.

“Both the ISCHEMIA and POST-PCI trials show the benefits of a ‘less is more’ concept (i.e., if more invasive strategies or testing are performed less frequently, it will result in better patient outcomes),” the authors wrote. Although characteristics of the patients in these trials “were quite different, a more invasive therapeutic approach (in the ISCHEMIA trial) as well as a more aggressive follow-up approach (in the POST-PCI trial) did not provide an additional treatment effect beyond a conservative strategy on the basis of guideline-directed medical therapy.”

Results were presented at the annual congress of the European Society of Cardiology and published online simultaneously in the New England Journal of Medicine.
 

‘Compelling new evidence’

In an editorial accompanying the publication, Jacqueline E. Tamis-Holland, MD, Icahn School of Medicine at Mount Sinai, Mount Sinai Morningside Hospital, New York, also agreed that this new result “builds on the findings” from the ISCHEMIA trial. “Collectively, these trials highlight the lack of benefit of routine stress testing in asymptomatic patients.”

Dr. Tamis-Holland pointed out that many of the deaths in this trial occurred before the 1-year stress test, possibly related to stent thrombosis, and therefore would not have been prevented by routine testing at 1 year. And overall, event rates were “quite low, and most likely reflect adherence to guideline recommendations” in the trial. For example, 99% of patients were receiving statins, and 74% of the procedures used intravascular imaging for the PCI procedures, “a much greater proportion of use than most centers in the United States,” she noted.

“The POST-PCI trial provides compelling new evidence for a future class III recommendation for routine surveillance testing after PCI,” Dr. Tamis-Holland concluded “Until then, we must refrain from prescribing surveillance stress testing to our patients after PCI, in the absence of other clinical signs or symptoms suggestive of stent failure.”

Commenting on the results, B. Hadley Wilson, MD, executive vice chair of the Sanger Heart & Vascular Institute/Atrium Health, clinical professor of medicine at University of North Carolina at Chapel Hill, and vice president of the American College of Cardiology, said that for decades it’s been thought that patients who had high-risk PCI needed to be followed more closely for potential future events. 

“And it actually turned out there was no difference in outcomes between the groups,” he said in an interview.

“So, I think it’s a good study – well conducted, good numbers –  that answers the question that routine functional stress testing, even for high-risk PCI patients, is not effective or cost effective or beneficial on a yearly basis,” he said. “I think it will help frame care that patients will just be followed with best medical therapy and then if they have recurrence of symptoms they would be considered for further evaluation, either with stress testing or angiography.”
 

High-risk characteristics

Current guidelines do not advocate the use of routine stress testing after revascularization, the authors wrote in their paper. “However, surveillance with the use of imaging-based stress testing may be considered in high-risk patients at 6 months after a revascularization procedure (class IIb recommendation), and routine imaging-based stress testing may be considered at 1 year after PCI and more than 5 years after CABG [coronary artery bypass graft] (class IIb recommendation).”

But in real-world clinical practice, Dr. Park said, “follow-up strategy for patients who underwent PCI or CABG is still undetermined.” Particularly, “it could be more problematic in high-risk PCI patients with high-risk anatomical or clinical characteristics. Thus, we performed this POST-PCI trial comparing routine stress testing follow-up strategy versus standard-care follow-up strategy in high-risk PCI patients.”

The researchers randomly assigned 1,706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing, including nuclear stress testing, exercise electrocardiography, or stress echocardiography at 1 year, or to standard care alone.

High-risk anatomical features included left main or bifurcation disease; restenotic or long, diffuse lesions; or bypass graft disease. High-risk clinical characteristics included diabetes mellitus, chronic kidney disease, or enzyme-positive acute coronary syndrome.

Mean age of the patients was 64.7 years; 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents.

At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval, 0.61-1.35; P = .62). There were no between-group differences in the components of the primary outcome.

Secondary endpoints included invasive coronary angiography or repeat revascularization. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, −0.01 to 5.99 percentage points), and 8.1% and 5.8% of patients, respectively, had a repeat revascularization procedure (difference, 2.23 percentage points; 95% CI, −0.22 to 4.68 percentage points).

Positive results on stress tests were more common with nuclear imaging than with exercise ECG or stress echocardiography, the authors noted. Subsequent coronary angiography and repeat revascularization were more common in patients with positive results on nuclear stress imaging and exercise ECG than in those with discordant results between nuclear imaging and exercise ECG.

POST-PCI was funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical Company. Dr. Park reported grants from the Cardiovascular Research Foundation and Daewoong Pharmaceutical Company. Dr. Tamis-Holland reported “other” funding from Pfizer  outside the submitted work. Dr. Wilson reported no relevant disclosures.

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

New randomized trial results show no benefit in clinical outcomes from active surveillance using functional testing over usual care among high-risk patients with previous percutaneous coronary intervention (PCI).

At 2 years, there was no difference in a composite outcome of death from any cause, MI, or hospitalization for unstable angina between patients who had routine functional testing at 1 year and patients receiving standard care in the POST-PCI trial.

“Our trial does not support active surveillance with routine functional testing for follow-up strategy in high-risk patients who undergo PCI,” first author Duk-Woo Park, MD, division of cardiology, Asan Medical Center, University of Ulsan, Seoul, South Korea, said in an interview.

The researchers said their results should be interpreted in the context of previous findings from the ISCHEMIA trial that showed no difference in death or ischemic events with an initial invasive versus an initial conservative approach in patients with stable coronary artery disease and moderate to severe ischemia on stress testing.

“Both the ISCHEMIA and POST-PCI trials show the benefits of a ‘less is more’ concept (i.e., if more invasive strategies or testing are performed less frequently, it will result in better patient outcomes),” the authors wrote. Although characteristics of the patients in these trials “were quite different, a more invasive therapeutic approach (in the ISCHEMIA trial) as well as a more aggressive follow-up approach (in the POST-PCI trial) did not provide an additional treatment effect beyond a conservative strategy on the basis of guideline-directed medical therapy.”

Results were presented at the annual congress of the European Society of Cardiology and published online simultaneously in the New England Journal of Medicine.
 

‘Compelling new evidence’

In an editorial accompanying the publication, Jacqueline E. Tamis-Holland, MD, Icahn School of Medicine at Mount Sinai, Mount Sinai Morningside Hospital, New York, also agreed that this new result “builds on the findings” from the ISCHEMIA trial. “Collectively, these trials highlight the lack of benefit of routine stress testing in asymptomatic patients.”

Dr. Tamis-Holland pointed out that many of the deaths in this trial occurred before the 1-year stress test, possibly related to stent thrombosis, and therefore would not have been prevented by routine testing at 1 year. And overall, event rates were “quite low, and most likely reflect adherence to guideline recommendations” in the trial. For example, 99% of patients were receiving statins, and 74% of the procedures used intravascular imaging for the PCI procedures, “a much greater proportion of use than most centers in the United States,” she noted.

“The POST-PCI trial provides compelling new evidence for a future class III recommendation for routine surveillance testing after PCI,” Dr. Tamis-Holland concluded “Until then, we must refrain from prescribing surveillance stress testing to our patients after PCI, in the absence of other clinical signs or symptoms suggestive of stent failure.”

Commenting on the results, B. Hadley Wilson, MD, executive vice chair of the Sanger Heart & Vascular Institute/Atrium Health, clinical professor of medicine at University of North Carolina at Chapel Hill, and vice president of the American College of Cardiology, said that for decades it’s been thought that patients who had high-risk PCI needed to be followed more closely for potential future events. 

“And it actually turned out there was no difference in outcomes between the groups,” he said in an interview.

“So, I think it’s a good study – well conducted, good numbers –  that answers the question that routine functional stress testing, even for high-risk PCI patients, is not effective or cost effective or beneficial on a yearly basis,” he said. “I think it will help frame care that patients will just be followed with best medical therapy and then if they have recurrence of symptoms they would be considered for further evaluation, either with stress testing or angiography.”
 

High-risk characteristics

Current guidelines do not advocate the use of routine stress testing after revascularization, the authors wrote in their paper. “However, surveillance with the use of imaging-based stress testing may be considered in high-risk patients at 6 months after a revascularization procedure (class IIb recommendation), and routine imaging-based stress testing may be considered at 1 year after PCI and more than 5 years after CABG [coronary artery bypass graft] (class IIb recommendation).”

But in real-world clinical practice, Dr. Park said, “follow-up strategy for patients who underwent PCI or CABG is still undetermined.” Particularly, “it could be more problematic in high-risk PCI patients with high-risk anatomical or clinical characteristics. Thus, we performed this POST-PCI trial comparing routine stress testing follow-up strategy versus standard-care follow-up strategy in high-risk PCI patients.”

The researchers randomly assigned 1,706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing, including nuclear stress testing, exercise electrocardiography, or stress echocardiography at 1 year, or to standard care alone.

High-risk anatomical features included left main or bifurcation disease; restenotic or long, diffuse lesions; or bypass graft disease. High-risk clinical characteristics included diabetes mellitus, chronic kidney disease, or enzyme-positive acute coronary syndrome.

Mean age of the patients was 64.7 years; 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents.

At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval, 0.61-1.35; P = .62). There were no between-group differences in the components of the primary outcome.

Secondary endpoints included invasive coronary angiography or repeat revascularization. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, −0.01 to 5.99 percentage points), and 8.1% and 5.8% of patients, respectively, had a repeat revascularization procedure (difference, 2.23 percentage points; 95% CI, −0.22 to 4.68 percentage points).

Positive results on stress tests were more common with nuclear imaging than with exercise ECG or stress echocardiography, the authors noted. Subsequent coronary angiography and repeat revascularization were more common in patients with positive results on nuclear stress imaging and exercise ECG than in those with discordant results between nuclear imaging and exercise ECG.

POST-PCI was funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical Company. Dr. Park reported grants from the Cardiovascular Research Foundation and Daewoong Pharmaceutical Company. Dr. Tamis-Holland reported “other” funding from Pfizer  outside the submitted work. Dr. Wilson reported no relevant disclosures.

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

Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and also in mortality in those aged younger than 70.

The DANCAVAS study was presented at the annual congress of the European Society of Cardiology, being held in Barcelona. It was also simultaneously published online in The New England Journal of Medicine.

“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Denmark, told this news organization.

“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/MI/stroke was significantly reduced by 7%.”

He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”

Dr. Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible, and our study suggests it would be cost effective compared to cancer screening,” he said.

Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”

The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.

Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.

In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2,106 men (12.6%) in the invited group and 3,915 men (13.1%) in the control group (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .06).

The hazard ratio for stroke in the invited group, compared with the control group, was 0.93 (95% confidence interval, 0.86-0.99); for MI, 0.91 (95% CI, 0.81-1.03); for aortic dissection, 0.95 (95% CI, 0.61-1.49); and for aortic rupture, 0.81 (95% CI, 0.49-1.35).

The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI, 0.89-0.97).

There were no significant between-group differences in safety outcomes.

Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI, 0.83-0.96), with no effect in men aged 70-74.

Other findings showed that in the group invited to screening, there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54) but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.  

In terms of cost-effectiveness, the total additional health care costs were €207 ($206 U.S.) per person in the invited group, which included the screening, medication, and all physician and hospital visits.

The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9,075 ($9,043) per QALY in the whole cohort and €3,860 ($3,846) in the men aged 65-69.

Dr. Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.

“This study is a step in the right direction,” Dr. Diederichsen said in an interview. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”

He said the study had also collected some data on younger men – aged 60-64 – and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
 

Increased medical therapy

Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Ont., congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”

“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.

Dr. Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.

“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some health care systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group – perhaps cigarette smokers – could have conserved additional resources,” she suggested.

Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.

Dr. Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74. 

Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.

Susanna Price, MD, Royal Brompton Hospital, London, and cochair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.

“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented.

“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”

Also commenting for this news organization, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”

Dr. Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AFib.

The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.

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

Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and also in mortality in those aged younger than 70.

The DANCAVAS study was presented at the annual congress of the European Society of Cardiology, being held in Barcelona. It was also simultaneously published online in The New England Journal of Medicine.

“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Denmark, told this news organization.

“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/MI/stroke was significantly reduced by 7%.”

He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”

Dr. Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible, and our study suggests it would be cost effective compared to cancer screening,” he said.

Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”

The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.

Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.

In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2,106 men (12.6%) in the invited group and 3,915 men (13.1%) in the control group (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .06).

The hazard ratio for stroke in the invited group, compared with the control group, was 0.93 (95% confidence interval, 0.86-0.99); for MI, 0.91 (95% CI, 0.81-1.03); for aortic dissection, 0.95 (95% CI, 0.61-1.49); and for aortic rupture, 0.81 (95% CI, 0.49-1.35).

The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI, 0.89-0.97).

There were no significant between-group differences in safety outcomes.

Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI, 0.83-0.96), with no effect in men aged 70-74.

Other findings showed that in the group invited to screening, there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54) but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.  

In terms of cost-effectiveness, the total additional health care costs were €207 ($206 U.S.) per person in the invited group, which included the screening, medication, and all physician and hospital visits.

The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9,075 ($9,043) per QALY in the whole cohort and €3,860 ($3,846) in the men aged 65-69.

Dr. Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.

“This study is a step in the right direction,” Dr. Diederichsen said in an interview. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”

He said the study had also collected some data on younger men – aged 60-64 – and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
 

Increased medical therapy

Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Ont., congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”

“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.

Dr. Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.

“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some health care systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group – perhaps cigarette smokers – could have conserved additional resources,” she suggested.

Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.

Dr. Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74. 

Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.

Susanna Price, MD, Royal Brompton Hospital, London, and cochair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.

“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented.

“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”

Also commenting for this news organization, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”

Dr. Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AFib.

The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.

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

Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and also in mortality in those aged younger than 70.

The DANCAVAS study was presented at the annual congress of the European Society of Cardiology, being held in Barcelona. It was also simultaneously published online in The New England Journal of Medicine.

“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Denmark, told this news organization.

“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/MI/stroke was significantly reduced by 7%.”

He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”

Dr. Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible, and our study suggests it would be cost effective compared to cancer screening,” he said.

Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”

The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.

Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.

In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2,106 men (12.6%) in the invited group and 3,915 men (13.1%) in the control group (hazard ratio, 0.95; 95% confidence interval, 0.90-1.00; P = .06).

The hazard ratio for stroke in the invited group, compared with the control group, was 0.93 (95% confidence interval, 0.86-0.99); for MI, 0.91 (95% CI, 0.81-1.03); for aortic dissection, 0.95 (95% CI, 0.61-1.49); and for aortic rupture, 0.81 (95% CI, 0.49-1.35).

The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI, 0.89-0.97).

There were no significant between-group differences in safety outcomes.

Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI, 0.83-0.96), with no effect in men aged 70-74.

Other findings showed that in the group invited to screening, there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54) but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.  

In terms of cost-effectiveness, the total additional health care costs were €207 ($206 U.S.) per person in the invited group, which included the screening, medication, and all physician and hospital visits.

The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9,075 ($9,043) per QALY in the whole cohort and €3,860 ($3,846) in the men aged 65-69.

Dr. Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.

“This study is a step in the right direction,” Dr. Diederichsen said in an interview. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”

He said the study had also collected some data on younger men – aged 60-64 – and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
 

Increased medical therapy

Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Ont., congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”

“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.

Dr. Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.

“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some health care systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group – perhaps cigarette smokers – could have conserved additional resources,” she suggested.

Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.

Dr. Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74. 

Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.

Susanna Price, MD, Royal Brompton Hospital, London, and cochair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.

“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented.

“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”

Also commenting for this news organization, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”

Dr. Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AFib.

The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.

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

Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.

The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.

There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.

Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.

“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”

The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.

Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.

This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.

“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.

Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”

Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.

In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”

The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”

Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.

Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.

Detailed results

Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.

The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.

During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.

LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.

With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.

Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.

Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
 

‘Modest’ degree of CAD?

An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.

“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.

He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”

Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.

He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.

The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”

George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.

Copyright American Heart Association copyright American Heart Association copyright American Heart Association

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

Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.

The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.

There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.

Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.

“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”

The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.

Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.

This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.

“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.

Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”

Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.

In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”

The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”

Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.

Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.

Detailed results

Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.

The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.

During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.

LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.

With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.

Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.

Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
 

‘Modest’ degree of CAD?

An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.

“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.

He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”

Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.

He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.

The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”

George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.

Copyright American Heart Association copyright American Heart Association copyright American Heart Association

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

Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.

The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.

There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.

Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.

“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”

The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.

Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.

This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.

“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.

Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”

Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.

In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”

The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”

Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.

Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.

Detailed results

Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.

The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.

During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.

LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.

With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.

Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.

Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
 

‘Modest’ degree of CAD?

An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.

“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.

He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”

Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.

He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.

The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”

George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.

Copyright American Heart Association copyright American Heart Association copyright American Heart Association

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

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

Video-based artificial intelligence provided a more accurate and consistent reading of echocardiograms than did experienced sonographers in a blinded trial, a result suggesting that this technology is no longer experimental.

“We are planning to deploy this at Cedars, so this is essentially ready for use,” said David Ouyang, MD, who is affiliated with the Cedars-Sinai Medical School and is an instructor of cardiology at the University of California, both in Los Angeles.

The primary outcome of this trial, called EchoNet-RCT, was the proportion of cases in which cardiologists changed the left ventricular ejection fraction (LVEF) reading by more than 5%. They were blinded to the origin of the reports.

This endpoint was reached in 27.2% of reports generated by sonographers but just 16.8% of reports generated by AI, a mean difference of 10.5% (P < .001).

The AI tested in the trial is called EchoNet-Dynamic. It employs a video-based deep learning algorithm that permits beat-by-beat evaluation of ejection fraction. The specifics of this system were described in a study published 2 years ago in Nature. In that evaluation of the model training set, the absolute error rate was 6% in the more than 10,000 annotated echocardiogram videos.
 

Echo-Net is first blinded AI echo trial

Although AI is already being employed for image evaluation in many areas of medicine, the EchoNet-RCT study “is the first blinded trial of AI in cardiology,” Dr. Ouyang said. Indeed, he noted that no prior study has even been randomized.

After a run-in period, 3,495 echocardiograms were randomizly assigned to be read by AI or by a sonographer. The reports generated by these two approaches were then evaluated by the blinded cardiologists. The sonographers and the cardiologists participating in this study had a mean of 14.1 years and 12.7 years of experience, respectively.

Each reading by both sonographers and AI was based on a single beat, but this presumably was a relative handicap for the potential advantage of AI technology, which is capable of evaluating ejection fraction across multiple cardiac cycles. The evaluation of multiple cycles has been shown previously to improve accuracy, but it is tedious and not commonly performed in routine practice, according to Dr. Ouyang.
 

AI favored for all major endpoints

The superiority of AI was calculated after noninferiority was demonstrated. AI also showed superiority for the secondary safety outcome which involved a test-retest evaluation. Historical AI and sonographer echocardiogram reports were again blindly assessed. Although the retest variability was lower for both (6.29% vs. 7.23%), the difference was still highly significant in favor of AI (P < .001)

The relative efficiency of AI to sonographer assessment was also tested and showed meaningful reductions in work time. While AI eliminates the labor of the sonographer completely (0 vs. a median of 119 seconds, P < .001), it was also associated with a highly significant reduction in median cardiologist time spent on echo evaluation (54 vs. 64 seconds, P < .001).

Assuming that AI is integrated into the routine workflow of a busy center, AI “could be very effective at not only improving the quality of echo reading output but also increasing efficiencies in time and effort spent by sonographers and cardiologists by simplifying otherwise tedious but important tasks,” Dr. Ouyang said.

The trial enrolled a relatively typical population. The median age was 66 years, 57% were male, and comorbidities such as diabetes and chronic kidney disease were common. When AI was compared with sonographer evaluation in groups stratified by these variables as well as by race, image quality, and location of the evaluation (inpatient vs. outpatient), the advantage of AI was consistent.

Cardiologists cannot detect AI-read echos

Identifying potential limitations of this study, James D. Thomas, MD, professor of medicine, Northwestern University, Chicago, pointed out that it was a single-center trial, and he questioned a potential bias from cardiologists able to guess accurately which of the reports they were evaluating were generated by AI.

Dr. Ouyang acknowledged that this study was limited to patients at UCLA, but he pointed out that the training model was developed at Stanford (Calif.) University, so there were two sets of patients involved in testing the machine learning algorithm. He also noted that it was exceptionally large, providing a robust dataset.

As for the bias, this was evaluated as predefined endpoint.

“We asked the cardiologists to tell us [whether] they knew which reports were generated by AI,” Dr. Ouyang said. In 43% of cases, they reported they were not sure. However, when they did express confidence that the report was generated by AI, they were correct in only 32% of the cases and incorrect in 24%. Dr. Ouyang suggested these numbers argue against a substantial role for a bias affecting the trial results.

Dr. Thomas, who has an interest in the role of AI for cardiology, cautioned that there are “technical, privacy, commercial, maintenance, and regulatory barriers” that must be circumvented before AI is widely incorporated into clinical practice, but he praised this blinded trial for advancing the field. Even accounting for any limitations, he clearly shared Dr. Ouyang’s enthusiasm about the future of AI for EF assessment.

Dr. Ouyang reports financial relationships with EchoIQ, Ultromics, and InVision. Dr. Thomas reports financial relationships with Abbott, GE, egnite, EchoIQ, and Caption Health.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

• High-dose furosemide after cardiac surgery is associated with increased mortality and other adverse outcomes.

Why this matters

• The influence of furosemide on prognosis after cardiac surgery is not fully understood.
• The current findings suggest that high-dose furosemide after cardiac surgery is associated with increased risk for death and other adverse events and therefore should be used cautiously in that setting.

Study design

• The retrospective cohort of 6,752 cardiac surgery patients was divided into two groups according to average daily furosemide dosage after cardiac surgery: less than 20 mg (low-dose group, n = 6,033) and at least 20 mg (high-dose group, n = 719).
• The group were compared for total furosemide dose, total furosemide dose of at least 200 mg, total dose of furosemide by patient weight, and average daily furosemide dose of at least 20 mg.
• The primary outcomes were in-hospital mortality and mortality at 1 year after cardiac surgery. Secondary outcomes were length of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours.
• The study excluded patients aged younger than 18 whose weight data was missing or who had more than 5% of their data missing.

Key results

• Patients in the high-dose furosemide group tended to be older and have a higher body mass index (BMI) and higher rates of diabetes, chronic pulmonary diseases, heart failure, renal failure, blood transfusion, vasopressor use, and valvular surgery.
• They also tended have higher white cell counts and higher levels of blood urea nitrogen, creatinine, glucose, and lactate.
• Those in the high-dose group also were on vasopressors and ventilatory support longer.
• In adjusted multivariate analysis, increased in-hospital mortality was associated with average daily furosemide dose, average daily dose of at least 20 mg/d, and total dose of at least 200 mg.
• Increased mortality at 1 year was associated with total furosemide dose and average daily furosemide dose.
• Significant multivariate predictors of hospital stay of at least 14 days, length of ICU stay of at least 3 days, and mechanical ventilation for at least 48 hours after cardiac surgery included total furosemide dose, total dose by weight, average daily furosemide dose of at least 20 mg/d, and total dose of at least 200 mg.
• In subgroup analyses, average daily furosemide dose of at least 20 mg/d significantly increased risk for in-hospital mortality among patients younger than 60 years or with BMI of at least 28 who received vasopressors or blood transfusions, those with renal failure, and those with heart failure not involving congestion.

Limitations

• No limitations were discussed.

Disclosures

• The study was supported by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Jiangsu Postdoctoral Science Foundation.
• The authors declared that they have no competing interests.

This is a summary of a preprint research study, “Association between furosemide administration and outcomes in patients undergoing cardiac surgery,” from Jinghang Li, First Affiliated Hospital of Nanjing (China) Medical University, and colleagues on published on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com. A version of this article first appeared on Medscape.com.

A multibiomarker risk score helps predict increased risk for future cardiovascular (CV) events as well as high-risk anatomy at revascularization in stable patients with atherosclerotic cardiovascular disease (ASCVD), a FOURIER trial analysis suggests.

The risk score incorporates high-sensitivity C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), and growth differentiation factor 15 (GDF-15).

These routine biomarkers of inflammation and fibrosis, ventricular strain, and myocardial injury are individually associated with incident CV in stable ASCVD and were shown in earlier work to be a multimarker score to predict CV events in patients stabilized after an acute coronary syndrome in the IMPROVE-IT trial.

Validating the score, however, wasn’t really the intent here, explained senior author Brian Bergmark, MD, with the TIMI Study Group, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston.

“We know broadly speaking people with high troponin, BNP, et cetera, are going to have broadly defined clinical events like MIs [myocardial infarctions], death. And we also know on a granular level at a single time point that people who, for example, get a coronary CT scan and have a contemporary troponin level tend to have a little bit more coronary disease,” he said.

“But that leaves this broad swath of, what if we follow people over time? Can biomarkers in some form actually predict specific coronary anatomical characteristics and revascularization procedures in conjunction with clinical events?” Dr. Bergmark continued. “That’s sort of an untouched link or translational step between some of the granular data and these clinical events.”

As published in the Journal of the American College of Cardiology, the post hoc study analyzed baseline blood samples from 21,644 FOURIER participants and adapted the previously studied multimarker score to use hsTnI in place of high-sensitivity troponin T (hsTnT). One point was assigned for each elevated biomarker: hsCRP ≥ 2 mg/L, NT-proBNP ≥ 450 pg/mL, hsTnI ≥ 6 ng/L, and GDF-15 ≥ 1,800 pg/mL.

A total of 6,444 patients had a low score (0 points), 12,439 an intermediate score (1-2 points), and 2,761 a high score (3-4 points). Patients with higher biomarker scores were older and were more likely to have hypertension, diabetes, multiple prior MIs, heart failure, prior coronary artery bypass grafting (CABG), and peripheral artery disease but were less likely to have prior percutaneous coronary intervention (PCI).

Results showed a stepwise increase in 3-year risk for major coronary events (coronary death, MI, or coronary revascularization) from 7.3% with a low score to 11.3% with an intermediate score and 21.0% with a high score. A near tripling of risk remained in those with a high score after adjustment (hazard ratio, 2.90).

Individuals with a high score had twice the risk for any coronary revascularization (HR, 2.10) and complex revascularization (HR, 2.07), as well as increased risks for complex PCI (HR, 1.80), CABG (HR, 2.57), and in-stent restenosis (ISR) revascularization (HR, 1.78).

The study is the first to show an association of these biomarkers with future ISR revascularization in a broad cohort of patients with stable ASCVD, the investigators observe.

It could be a random signal, but “it’s one piece of data as people start to look at other datasets, as we start to understand who’s at risk for ISR, as we understand this disease entity that’s really a pandemic at this point,” Dr. Bergmark said, “I think this is one piece of the puzzle that’s novel.”

Compared with those with a low score, patients with a high biomarker score had significantly higher risks for left main disease greater than 50% (HR, 2.22; P = .003), multivessel disease (HR, 1.99; P < .001), and chronic total occlusion (HR, 2.50; P < .001) at the time of revascularization.

There was no significant interaction between the biomarker score and the effect of evolocumab used in the trial; however, the assessment had limited statistical power, the authors note.

Dr. Bergmark said that the results can inform trial design to select a population at risk for specific types of events and when trying to risk adjust in a population for reimbursement purposes to understand quality metrics, for example, for people coming back with ISR.

“I think refining risk estimates has broad applicability clinically and academically,” he added. “This is one step, with one dataset, pushing these typically broad clinical endpoints to be more specific.”

In an related editorial, Giles Montalescot, MD, PhD, Pitié-Salpêtrière Hospital, Paris, and colleagues write, “Not only does this study validate the multibiomarker score in a new cohort of patients and with new coronary-focused outcomes, but it also opens novel and interesting avenues, on a global approach of cardiovascular risk.”

Possibilities include using this or another multibiomarker risk score to streamline enrichment or selection criteria for a trial or as a surrogate endpoint in proof-of-concept trials to test a new drug aimed at reducing CV risk.

“Beyond clinical research, we could imagine in the future to base our therapeutic decisions on such a score, just like we decide anticoagulation in patients with atrial fibrillation according to the CHA₂DS₂-VASc score,” the editorialists say.

This being said, Dr. Montalescot and colleagues point out that the current multibiomarker risk score assigned equal prognostic value to each of the components, whereas IMPROVE-IT and FOURIER both showed that elevated hsTnT and NT-proBNP were associated with much higher hazard ratios than hsCRP and GDF-15.

Other limitations, they say, are that the categorical nature of the variables, albeit user friendly, prevent any subtle analysis; the score does not include biological risk factors; and questions remain about the impact of the lipid-lowering intervention across risk categories.

FOURIER was funded by Amgen. The TIMI Study Group has received institutional grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr. Bergmark reports grant support from Pfizer, Ionis, AstraZeneca, and Abbott Vascular; and consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark Pharmaceuticals. Dr. Montalescot reports research grants to his institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell Prothera, CSL Behring, Europa, Idorsia, IRIS-Servier, Medtronic, MSD, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.

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

A multibiomarker risk score helps predict increased risk for future cardiovascular (CV) events as well as high-risk anatomy at revascularization in stable patients with atherosclerotic cardiovascular disease (ASCVD), a FOURIER trial analysis suggests.

The risk score incorporates high-sensitivity C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), and growth differentiation factor 15 (GDF-15).

These routine biomarkers of inflammation and fibrosis, ventricular strain, and myocardial injury are individually associated with incident CV in stable ASCVD and were shown in earlier work to be a multimarker score to predict CV events in patients stabilized after an acute coronary syndrome in the IMPROVE-IT trial.

Validating the score, however, wasn’t really the intent here, explained senior author Brian Bergmark, MD, with the TIMI Study Group, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston.

“We know broadly speaking people with high troponin, BNP, et cetera, are going to have broadly defined clinical events like MIs [myocardial infarctions], death. And we also know on a granular level at a single time point that people who, for example, get a coronary CT scan and have a contemporary troponin level tend to have a little bit more coronary disease,” he said.

“But that leaves this broad swath of, what if we follow people over time? Can biomarkers in some form actually predict specific coronary anatomical characteristics and revascularization procedures in conjunction with clinical events?” Dr. Bergmark continued. “That’s sort of an untouched link or translational step between some of the granular data and these clinical events.”

As published in the Journal of the American College of Cardiology, the post hoc study analyzed baseline blood samples from 21,644 FOURIER participants and adapted the previously studied multimarker score to use hsTnI in place of high-sensitivity troponin T (hsTnT). One point was assigned for each elevated biomarker: hsCRP ≥ 2 mg/L, NT-proBNP ≥ 450 pg/mL, hsTnI ≥ 6 ng/L, and GDF-15 ≥ 1,800 pg/mL.

A total of 6,444 patients had a low score (0 points), 12,439 an intermediate score (1-2 points), and 2,761 a high score (3-4 points). Patients with higher biomarker scores were older and were more likely to have hypertension, diabetes, multiple prior MIs, heart failure, prior coronary artery bypass grafting (CABG), and peripheral artery disease but were less likely to have prior percutaneous coronary intervention (PCI).

Results showed a stepwise increase in 3-year risk for major coronary events (coronary death, MI, or coronary revascularization) from 7.3% with a low score to 11.3% with an intermediate score and 21.0% with a high score. A near tripling of risk remained in those with a high score after adjustment (hazard ratio, 2.90).

Individuals with a high score had twice the risk for any coronary revascularization (HR, 2.10) and complex revascularization (HR, 2.07), as well as increased risks for complex PCI (HR, 1.80), CABG (HR, 2.57), and in-stent restenosis (ISR) revascularization (HR, 1.78).

The study is the first to show an association of these biomarkers with future ISR revascularization in a broad cohort of patients with stable ASCVD, the investigators observe.

It could be a random signal, but “it’s one piece of data as people start to look at other datasets, as we start to understand who’s at risk for ISR, as we understand this disease entity that’s really a pandemic at this point,” Dr. Bergmark said, “I think this is one piece of the puzzle that’s novel.”

Compared with those with a low score, patients with a high biomarker score had significantly higher risks for left main disease greater than 50% (HR, 2.22; P = .003), multivessel disease (HR, 1.99; P < .001), and chronic total occlusion (HR, 2.50; P < .001) at the time of revascularization.

There was no significant interaction between the biomarker score and the effect of evolocumab used in the trial; however, the assessment had limited statistical power, the authors note.

Dr. Bergmark said that the results can inform trial design to select a population at risk for specific types of events and when trying to risk adjust in a population for reimbursement purposes to understand quality metrics, for example, for people coming back with ISR.

“I think refining risk estimates has broad applicability clinically and academically,” he added. “This is one step, with one dataset, pushing these typically broad clinical endpoints to be more specific.”

In an related editorial, Giles Montalescot, MD, PhD, Pitié-Salpêtrière Hospital, Paris, and colleagues write, “Not only does this study validate the multibiomarker score in a new cohort of patients and with new coronary-focused outcomes, but it also opens novel and interesting avenues, on a global approach of cardiovascular risk.”

Possibilities include using this or another multibiomarker risk score to streamline enrichment or selection criteria for a trial or as a surrogate endpoint in proof-of-concept trials to test a new drug aimed at reducing CV risk.

“Beyond clinical research, we could imagine in the future to base our therapeutic decisions on such a score, just like we decide anticoagulation in patients with atrial fibrillation according to the CHA₂DS₂-VASc score,” the editorialists say.

This being said, Dr. Montalescot and colleagues point out that the current multibiomarker risk score assigned equal prognostic value to each of the components, whereas IMPROVE-IT and FOURIER both showed that elevated hsTnT and NT-proBNP were associated with much higher hazard ratios than hsCRP and GDF-15.

Other limitations, they say, are that the categorical nature of the variables, albeit user friendly, prevent any subtle analysis; the score does not include biological risk factors; and questions remain about the impact of the lipid-lowering intervention across risk categories.

FOURIER was funded by Amgen. The TIMI Study Group has received institutional grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr. Bergmark reports grant support from Pfizer, Ionis, AstraZeneca, and Abbott Vascular; and consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark Pharmaceuticals. Dr. Montalescot reports research grants to his institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell Prothera, CSL Behring, Europa, Idorsia, IRIS-Servier, Medtronic, MSD, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.

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

A multibiomarker risk score helps predict increased risk for future cardiovascular (CV) events as well as high-risk anatomy at revascularization in stable patients with atherosclerotic cardiovascular disease (ASCVD), a FOURIER trial analysis suggests.

The risk score incorporates high-sensitivity C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), and growth differentiation factor 15 (GDF-15).

These routine biomarkers of inflammation and fibrosis, ventricular strain, and myocardial injury are individually associated with incident CV in stable ASCVD and were shown in earlier work to be a multimarker score to predict CV events in patients stabilized after an acute coronary syndrome in the IMPROVE-IT trial.

Validating the score, however, wasn’t really the intent here, explained senior author Brian Bergmark, MD, with the TIMI Study Group, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston.

“We know broadly speaking people with high troponin, BNP, et cetera, are going to have broadly defined clinical events like MIs [myocardial infarctions], death. And we also know on a granular level at a single time point that people who, for example, get a coronary CT scan and have a contemporary troponin level tend to have a little bit more coronary disease,” he said.

“But that leaves this broad swath of, what if we follow people over time? Can biomarkers in some form actually predict specific coronary anatomical characteristics and revascularization procedures in conjunction with clinical events?” Dr. Bergmark continued. “That’s sort of an untouched link or translational step between some of the granular data and these clinical events.”

As published in the Journal of the American College of Cardiology, the post hoc study analyzed baseline blood samples from 21,644 FOURIER participants and adapted the previously studied multimarker score to use hsTnI in place of high-sensitivity troponin T (hsTnT). One point was assigned for each elevated biomarker: hsCRP ≥ 2 mg/L, NT-proBNP ≥ 450 pg/mL, hsTnI ≥ 6 ng/L, and GDF-15 ≥ 1,800 pg/mL.

A total of 6,444 patients had a low score (0 points), 12,439 an intermediate score (1-2 points), and 2,761 a high score (3-4 points). Patients with higher biomarker scores were older and were more likely to have hypertension, diabetes, multiple prior MIs, heart failure, prior coronary artery bypass grafting (CABG), and peripheral artery disease but were less likely to have prior percutaneous coronary intervention (PCI).

Results showed a stepwise increase in 3-year risk for major coronary events (coronary death, MI, or coronary revascularization) from 7.3% with a low score to 11.3% with an intermediate score and 21.0% with a high score. A near tripling of risk remained in those with a high score after adjustment (hazard ratio, 2.90).

Individuals with a high score had twice the risk for any coronary revascularization (HR, 2.10) and complex revascularization (HR, 2.07), as well as increased risks for complex PCI (HR, 1.80), CABG (HR, 2.57), and in-stent restenosis (ISR) revascularization (HR, 1.78).

The study is the first to show an association of these biomarkers with future ISR revascularization in a broad cohort of patients with stable ASCVD, the investigators observe.

It could be a random signal, but “it’s one piece of data as people start to look at other datasets, as we start to understand who’s at risk for ISR, as we understand this disease entity that’s really a pandemic at this point,” Dr. Bergmark said, “I think this is one piece of the puzzle that’s novel.”

Compared with those with a low score, patients with a high biomarker score had significantly higher risks for left main disease greater than 50% (HR, 2.22; P = .003), multivessel disease (HR, 1.99; P < .001), and chronic total occlusion (HR, 2.50; P < .001) at the time of revascularization.

There was no significant interaction between the biomarker score and the effect of evolocumab used in the trial; however, the assessment had limited statistical power, the authors note.

Dr. Bergmark said that the results can inform trial design to select a population at risk for specific types of events and when trying to risk adjust in a population for reimbursement purposes to understand quality metrics, for example, for people coming back with ISR.

“I think refining risk estimates has broad applicability clinically and academically,” he added. “This is one step, with one dataset, pushing these typically broad clinical endpoints to be more specific.”

In an related editorial, Giles Montalescot, MD, PhD, Pitié-Salpêtrière Hospital, Paris, and colleagues write, “Not only does this study validate the multibiomarker score in a new cohort of patients and with new coronary-focused outcomes, but it also opens novel and interesting avenues, on a global approach of cardiovascular risk.”

Possibilities include using this or another multibiomarker risk score to streamline enrichment or selection criteria for a trial or as a surrogate endpoint in proof-of-concept trials to test a new drug aimed at reducing CV risk.

“Beyond clinical research, we could imagine in the future to base our therapeutic decisions on such a score, just like we decide anticoagulation in patients with atrial fibrillation according to the CHA₂DS₂-VASc score,” the editorialists say.

This being said, Dr. Montalescot and colleagues point out that the current multibiomarker risk score assigned equal prognostic value to each of the components, whereas IMPROVE-IT and FOURIER both showed that elevated hsTnT and NT-proBNP were associated with much higher hazard ratios than hsCRP and GDF-15.

Other limitations, they say, are that the categorical nature of the variables, albeit user friendly, prevent any subtle analysis; the score does not include biological risk factors; and questions remain about the impact of the lipid-lowering intervention across risk categories.

FOURIER was funded by Amgen. The TIMI Study Group has received institutional grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr. Bergmark reports grant support from Pfizer, Ionis, AstraZeneca, and Abbott Vascular; and consulting fees from Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark Pharmaceuticals. Dr. Montalescot reports research grants to his institution or consulting/lecture fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cell Prothera, CSL Behring, Europa, Idorsia, IRIS-Servier, Medtronic, MSD, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

After 2 years of virtual gatherings, the annual European Society of Cardiology Congress 2022 is back and celebrating its 70th birthday live in the raucously beautiful city of Barcelona.

Much of the upcoming event, scheduled for Aug. 26 to 29, however, will also be broadcast online, and the full program will be available on-demand after the meeting.

The hybrid format is intentional, leveraging the social interaction that only live meetings can provide and the global reach of online access, Program Committee Chair Stephan Windecker, MD, Bern University Hospital, Switzerland, told this news organization.

“It enables a lot of people who, for some reason, cannot travel to still connect, and it also provides what we’ve done in the past, but I think in a more natural way of doing it,” he said. “You can connect later on again, read, digest, look at sessions that you may have missed, and that’s a nice experience to take advantage of.”

Thus far, early registrations are favoring the sunny climes, with about 14,000 onsite and 4,200 online attendees.

This year’s spotlight theme is cardiac imaging, with programming throughout the Congress devoted to its role in diagnosis, treatment, follow-up, and, increasingly, guidance of interventions.

“Particularly as it relates to the transcatheter heart valves, it’s really a new discipline, and I think you can’t overemphasize that enough, because the interventional result directly depends on the quality of imaging,” Dr. Windecker said. “This will certainly logarithmically increase during the next few years.”

The always highly anticipated Hot Line sessions mushroomed this year to 10, featuring 36 studies, up from just 4 sessions and 20 studies last year.

“Especially during the COVID pandemic, many investigators and trialists experienced difficulties in recruitment, difficulties in terms of also personnel shortages, and so on. So really, we feel very privileged at the large number of submissions,” he said. “I think there are really very interesting ones, which we tried to spread throughout the 4 days.”
 

Hot Line sessions 1-5

Among the studies Dr. Windecker highlighted is TIME, which kicks off Hot Line 1 on Friday, Aug. 26, and aimed to establish whether antihypertensive medications taken at night are truly more cardioprotective than those taken in the morning.

The topic has been hotly debated, with proponents pointing to a near halving of mortality and cardiovascular events with bedtime dosing in the Hygia Chronotherapy trial. Skeptics question the validity and conduct of the trial, however, prompting an investigation by the European Heart Journal, which found no evidence of misconduct but has many looking for more definitive data.

Also in this session is SECURE, pitting a cardiovascular polypill that contains aspirin, ramipril, and atorvastatin against usual care in secondary prevention, and PERSPECTIVE, comparing the effects of sacubitril/valsartan with valsartan on cognitive function in patients with chronic heart failure and preserved ejection fraction (HFpEF).

Hot Line 2, the first of three Hot Lines taking place on Saturday, Aug. 27, features the Danish cardiovascular screening trial DANCAVAS, the phase 4 ADVOR trial of acetazolamide (Diamox) in acute decompensated heart failure (HF), and the DANFLU-1 trial of high- versus standard-dose influenza vaccine in the elderly.

Also on tap is the BOX trial, comparing two blood pressure and two oxygenation targets in comatose out-of-hospital cardiac arrest patients.

“It addresses an understudied patient population, and the second element is that sometimes things you do out of ordinary application – so, the application of oxygen – may have beneficial but also adverse impact,” Dr. Windecker said. “So, to study this in a randomized clinical trial is really important.”

Additionally, he highlighted REVIVED, which will be presented in Hot Line 3 and is the first trial to examine percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) versus OMT alone in the setting of severe ischemic cardiomyopathy.

“We have data from the STICH trial, where surgical revascularization was investigated in ischemic cardiomyopathy, but the open question is: What about PCI as revascularization?” Dr. Windecker said. “The other reason it’s interesting is that we have these evidence-based drugs that have dramatically improved outcomes in patients with heart failure, and REVIVED certainly has been conducted now in an era where at least some of these drugs are more systematically implemented.”

Rounding out this session are the Scottish ALL-HEART study of allopurinol in ischemic heart disease and EchoNet-RCT, looking at whether artificial intelligence (AI) can improve the accuracy of echocardiograms.

Hot Line 4 features DELIVER, a phase 3 trial of the SGLT2 inhibitor dapagliflozin (Farxiga) in HF with preserved or mildly reduced ejection fraction. Topline results, released in May, showed that the study has met its primary endpoint of cardiovascular death or worsening HF.

Dr. Windecker said DELIVER will be a “highlight” of the meeting, particularly because EMPEROR-Preserved, presented at ESC 2021, showed a benefit for another SGLT2 inhibitor, empagliflozin, in this very specific setting. Two prespecified analyses will also be presented, pooling data from EMPEROR-Preserved and from the DAPA-HF study of dapagliflozin in patients with reduced EF. “This will be a session very rich in terms of information.”

Another not-to-be-missed session is Hot Line 5, which will focus on antithrombotic therapy, according to Dr. Windecker, who will cochair the Sunday, Aug. 28 session.

First up is the investigator-initiated INVICTUS-VKA, testing rivaroxaban noninferiority versus standard vitamin K antagonists in patients with atrial fibrillation (AFib) and rheumatic heart disease, a setting in which non–vitamin K antagonists have not been sufficiently tested.

This is followed by three phase 2 trials – PACIFIC-AMI, PACIFIC-STROKE, and AXIOMATIC-SSP – investigating the novel factor XIa inhibitors BAY 2433334 and BMS-986177 in patients with myocardial infarction or stroke.
 

Hot Line sessions 6-10

Sunday’s Hot Line 6 takes another look at smartphone-based AFib screening in eBRAVE-HF, use of causal AI to improve the validity of cardiovascular risk prediction, and AI-enhanced detection of aortic stenosis.

Hot Line 7 rounds out the day, putting coronary imaging center stage. It includes perfusion scanning with MR or PET after a positive angiogram in DanNICAD-2, the PET tracer 18F-sodium fluoride as a marker of high-risk coronary plaques in patients with recent MIs in PREFFIR, and fractional flow reserve- versus angiography-guided PCI in acute MI with multivessel disease in FRAME-AMI.

After a weekend of top-notch science and, no doubt, a spot of revelry, the focus returns on Monday, Aug. 29 to three Hot Line sessions. The first of these, Hot Line 8, updates five clinical trials, including 5-year outcomes from ISCHEMIA-CKD EXTEND, 15-month results from MASTER DAPT, and primary results from FOURIER-OLE, the open-label extension study of evolocumab out to 5 years in approximately 1,600 study participants.

The session closes out with causes of mortality in the FIDELITY trial of finerenone and a win-ratio analysis of PARADISE-MI.

Hot Line 9, billed as an “evidence synthesis on clinically important questions,” includes a Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis on the effects of statins on muscle symptoms and a meta-analysis of angiotensin-receptor blockers and beta-blockers in Marfan syndrome from the Marfan Treatment Trialists’ Collaboration.

Also featured is evidence on radial versus femoral access for coronary procedures, and PANTHER, a patient-level meta-analysis of aspirin or P2Y12 inhibitor monotherapy as secondary prevention in patients with established coronary artery disease.

COVID-19, deeply rooted in the minds of attendees and considered in 52 separate sessions, takes over the final Hot Line session of the Congress. Hot Line 10 will report on antithrombotic therapy in critically ill patients in COVID-PACT and on anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin alone or in combination with rivaroxaban in the ACT inpatient and outpatient trials. Although such early trials have been largely negative, the latest details will be interesting to see, Dr. Windecker suggested.

In terms of COVID-19 protocols, ESC will recommend but not mandate masks and will have test kits available should attendees wish to have a test or if they become symptomatic, he noted.
 

New guidelines released

Four new ESC guidelines will be released during the congress on cardio-oncology, ventricular arrhythmias and sudden cardiac death, pulmonary hypertension, and cardiovascular assessment and management of patients undergoing noncardiac surgery.

In addition to a guideline overview on Friday, one guideline will be featured each day in a 1-hour session, with additional time for discussions with guideline task force members, and six sessions devoted to the implementation of existing guidelines in clinical practice.

The ESC already has a position paper on cardio-oncology, but now, for the first time, has a full guideline with formal laws and level-of-evidence recommendations, Dr. Windecker pointed out.

“I think what will be the great asset, not only of the guideline but out of this emerging field, is that people in the future will probably not only be treated when it’s too late or suffer from toxicity but that there will be screening, and people will be aware before the implementation of therapy,” he added.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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