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ATLANTA — Beta-blockers have been a mainstay of therapy for patients who have revascularization after an acute myocardial infarction (MI), but people who have had smaller MIs and survive with preserved ejection fraction (EF) may be able to skip the beta-blockers and leave the hospital with one less prescription, a large, registry-based, open-label trial suggested.

The REDUCE-AMI trial randomized 5020 patients who had coronary angiography after an acute MI and had a left ventricular EF of 50% or greater, to either long-term treatment with the beta-blockers metoprolol or bisoprolol or no beta-blocker therapy.

After an average follow-up of 3.5 years, the rate of all-cause death or MI was 7.9% in the beta-blocker group and 8.3% in the no beta-blocker group, according to results presented at the American College of Cardiology meeting here.

The findings were published simultaneously online in the New England Journal of Medicine.

The results mean that cardiologists can consider subtracting long-term beta-blocker therapy from the medication list for a large number of patients with post-MI, lead study investigator Troels Yndigegn, MD, chief of cardiology at Skåne University Hospital in Lund, Sweden, told theheart.org | Medscape Cardiology.

"What we see today is that patients with myocardial infarction are healthier than they were 10, 20, or 30 years ago," he said. "This patient population is not that small actually. We see that up to 50% of patients with myocardial infarction fit this description of patients with preserved ejection fraction, so it's quite a large part of the population that will benefit from not having the side effects of unnecessary medication."

SWEDEHEART Registry

The study enrolled adults within a week after they had either an ST-elevation MI (STEMI) or non-STEMI, had coronary angiography during their hospitalization, and had an EF of 50% or greater confirmed on echocardiography. Percutaneous coronary intervention was done in 95.5% of the patients, and coronary-artery bypass grafting was done in 3.9%. At the time of discharge, 97.4% of the patients were also receiving aspirin, 95.8% were on a P2Y12 receptor blocker, 80.2% were on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, and 98.5% were on a statin.

The study ran from September 2017 through May 2023 and enrolled patients from 45 centers in Sweden, Estonia, and New Zealand, using data from the SWEDEHEART registry for the 38 centers in Sweden. Some 99.7% of patients completed follow-up.

In the beta-blocker group, 62.2% received metoprolol and 37.8% bisoprolol.

The study also included six secondary endpoints, all of which saw similar outcomes. For all-cause death alone, the rates were 3.9% and 4.1% in the beta-blocker and no beta-blocker groups (P = .66). Rates of hospital admission, either because of atrial fibrillation or heart failure, were also similar between the two groups: 1.1% and 1.4% (P = .37) for the former; and 0.8% and 0.9% for the latter (P = .76). Safety endpoints were also similar, Yndigegn noted.

"On the other hand," Yndigegn told Medscape Medical News, "we cannot say that we didn't see a detrimental effect of beta-blocker therapy."

Reducing prescriptions in this patient population may be a desirable goal, he said. "These are healthy patients with a small risk," Yndigegn continued. "They had a small myocardial infarction, they are revascularized, and they want to go on living their lives as normal.

"The standard is, you are healthy one day, then you have a small myocardial infarction, and you're put on at least five more medications. Patients always ask us, 'Do we really need five medications for this small incident'?"

He added, "We cannot say that patients who are living an active life, who are doing secondary prevention with exercise, that when they're put on a beta-blocker, maybe they are not able to exercise," he added. "That could lead to a worse outcome for the patient, but we haven't proven that either."

Yndigegn acknowledged several limitations with the study. It was an open-label trial without blinding, the endpoints from registries were not reviewed for consistency, and it did not account for patients crossed over from one regimen to the other.

A 'Reductionist' Approach

Drug studies typically take an "additive" approach, said Wayne Batchelor, MD, director of interventional cardiology at the Inova Schar Heart and Vascular Institute in Fairfax, Virginia, and chair of the ACC's Interventional Council, in critiquing the REDUCE-AMI trial. "But the message of this study is that we might be able to have somewhat of a reductionist approach," he said.

"To me, the message here is that we can tell physicians and patients that — because one of the biggest challenges after a heart attack is that you're on like a gazillion medications — we can finally start to say with some degree of confidence that if your left ventricle ejection fraction is preserved greater than 50% and you don't have any other reason to be on a beta-blocker, you probably don't need to throw that in."

However, Batchelor added a word of caution. "This does not address the midrange ejection fraction patients — patients whose EF is 40%-49%."

Yndigegn had no relevant financial relationships. Batchelor had no relevant financial relationships to disclose.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.