No Benefit for Beta-Blockers After Acute MI

In patients with acute myocardial infarction with preserved ejection fraction, long-term use of beta-blockers does not reduce the risk of death or a second heart attack, according to results from the REDUCE-AMI study.

“Similarly, there was no apparent benefit on any of the secondary or safety endpoints” across all prespecified subgroups, lead author Troels Yndigegn, MD, said at the recent 2024 annual scientific sessions of the American College of Cardiology (ACC).

“I think that, following this study, many doctors will not find an indication to routinely treat all their patients with beta-blockers following a heart attack,” Dr. Yndigegn, Lund University, Sweden, said in a statement.

Both US and European guidelines widely recommend beta-blockers use after myocardial infarction (MI) because of their efficacy in heart failure (HF) with reduced ejection fraction and a mortality benefit of about 20% post-MI, he noted. Most of the trials, however, involved large MIs with left ventricular dysfunction and were conducted in the 1980s before reperfusion, modern medical therapies, and secondary prevention.

Contemporary observational studies including acute MI patients with preserved ejection fraction have yielded conflicting results, prompting the study. The results were published simultaneously in the New England Journal of Medicine.

Clinical Endpoints

REDUCE-AMI enrolled 5020 patients at 45 centers in Sweden (95%), Estonia, and New Zealand who had a preserved ejection fraction of at least 50% and obstructive coronary artery disease. Data were collected in Sweden from the SWEDEHEART registry and other national registries and from electronic case-report forms and hospital records in Estonia and New Zealand.

Patients were randomized to no beta-blockers or either metoprolol to a target daily dose of at least 100 mg (62.2%) or 5 mg bisoprolol (37.8%). The median age was 65 years and 95.5% underwent percutaneous coronary intervention.

Over a median of 3.5 years follow-up, the primary endpoint of all-cause mortality or new MI occurred in 7.9% of the beta-blocker group and 8.3% of the no-beta-blocker group (P = 0.64).

There were 97 deaths from any cause with beta-blockers and 103 deaths without (P = 0.66).

“This study, to me, its value is that it allows us to confidently reduce the number of medications in this particular subgroup, who probably don’t stand to benefit. (That’s) hugely important because we’ve now got six or seven medications these patients are going to be on,” Wayne Batchelor, MD, chair of the ACC interventional council, told MedCentral.

At discharge, 97.4% of the patients were on aspirin, 95.8 % on a P2Y12 receptor blocker, 98.5% on a statin, and 80.2% on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker.

The median dose was 100 mg for metoprolol and 5 mg for bisoprolol. This reflects clinical practice where beta-blockers are typically underdosed, but normally physicians are instructed to push the dose up to the maximum dose, for example, up to 200 mg for metoprolol, Dr. Batchelor said. “It’s amazing how the two arms looked almost identical and it just makes me wonder if the dosing was lower than maybe we would have liked to have seen.”

Shifting to Tailored Beta-Blocker Use

Historically, clinicians routinely treated almost all people after MI with beta-blockers, but in the past 10 years, they have turned away from this in patients with preserved ejection fraction and little myocardial damage, observed Dr. Batchelor, system director of interventional cardiology, Inova Schar Heart and Vascular, Fairfax, Virginia.

“It used to be you’d get dinged by your hospital quality committees if you didn’t use beta-blockers after myocardial infarction and then we sort of refined that recommendation,” he said. “Of course, this study is going to really help us stand more firmly on the basis that it’s not needed in everyone and only in those with reduced ejection fraction.”

What’s unclear is how to treat patients with a mid-range ejection fraction of 40% to 49% post-MI, Dr. Batchelor observed.

“On average, those patients probably should and will be placed on a beta-blocker because the tendency is to err on the side of caution and treat based on the previous data that showed benefit of beta-blockers on all-comers that’s now refined by this study,” he said.

Not All Are Convinced to Peel Back Beta-Blockers

“We’re looking to get beta-blockers off but I don’t know that this particular study has 100% convinced me we should do it in normal ejection fraction right now,” Roxana Mehran, MD, professor of medicine, Icahn School of Medicine, Mount Sinai, New York, NY, said in an interview.

She questioned whether REDUCE-AMI enrolled a select population with only 22% women, 35% with ST-elevation MI, and most with 1- to 2-vessel disease. Additionally, the trial was powered to detect a whopping 25% reduction in the primary endpoint and assumed a 6% annual event rate but got a 3% event rate over the years.

“What you see if you look at the confidence interval (for the primary outcome) is that the hazard ratio is 0.96 but the lower limit is 0.79 and the upper limit is 1.16, which means that beta-blockers could be, at one end of the spectrum, 21% effective or 16% worse,” said Dr. Mehran, who served as one of the formal discussants for the trial.

“Overall, it looks like there was no difference in this patient population. That’s why I was saying we need to wait for more data before we change our guidelines,” she said. “And remember, that even if this is true, it would be in a very select patient population.”

New Data on the Horizon

The good news is that there are a handful of trials coming out questioning the role of beta-blockers post-MI, Dr. Mehran pointed out. The trials are detailed in an accompanying editorial and include: DANBLOCK, BETAMI, REBOOT, SMART DECISION, ABYSS, and ABBREVIATE.

“Given the difficulty of unambiguously showing an absence of benefit with beta-blocker therapy and the limitations of a single, somewhat underpowered, open-label trial, it may be too early to cut beta-blockers from the ‘secondary prevention team’ definitively,” wrote editorialist Philippe Gabriel Steg, MD, Universite Paris-Cite, France.

Disclosures: The study was funded by the Swedish Research Council, Swedish Heart Lung Foundation, and Stockholm County Council. Dr. Yndigegn reported having no disclosures. Dr. Batchelor reported consulting fees/honoraria from Abbott Laboratories, Boston Scientific, V-Wave Medical, Idorsia, Edwards, NovoNordisk and Medtronic Dr. Mehran reported relationships with multiple entities. Dr. Steg reported relationships with multiple entities.