Long-term treatment with beta-blockers may not lower the risk of death or myocardial infarction (MI) in patients with MI, a preserved left ventricular ejection fraction (LVEF) of ≥50% and coronary artery disease, according to the results of the REDUCE-AMI study, presented during a Late-Breaking Clinical Trial session at ACC.24 and published simultaneously in the New England Journal of Medicine.

The parallel-group, open-label trial, conducted from September 2017 through May 2023 at 45 centers across Sweden, Estonia and New Zealand randomly assigned 5,020 patients (median age 65, 22.5% women) with acute MI who had participated in the SWEDEHEART registry, undergone coronary angiography and had an LVEF ≥50% to long-term treatment with one of two beta-blockers – metoprolol or bisoprolol (median dose of metoprolol 100 mg and bisoprolol 5 mg) or to no beta-blocker treatment.

Results showed that at a median follow-up of 3.5 years, the primary composite endpoint of death from any cause or new MI occurred in 199 (7.9%) of patients in the beta-blocker group and 208 (8.3%) of patients in the no-beta-blocker group (hazard ratio, 0.96; 95% CI, 0.79-1.16; p=0.64).

Beta-blocker treatment did not lower the incidence of the secondary endpoints. Death from any cause occurred in 97 (3.9%) of patients in the beta-blocker group and 103 (4.1%) in the control group. Death from cardiovascular causes occurred in 38 (1.5%) and 33 (1.3%) respectively. MI occurred in 112 (4.5%) and 117 (4.7%), hospitalization for atrial fibrillation occurred in 27 (1.1%) and 34 (1.4%), and hospitalization for heart failure occurred in 20 (0.8%) and 22 (0.9%).

The occurrence of the safety endpoints was similar in the two groups. Hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope or implantation of a pacemaker occurred in 3.4% and 3.2% of the beta-blocker and control groups, respectively, while hospitalization for asthma or chronic obstructive pulmonary disease occurred in 0.6% of each group and hospitalization for stroke occurred in 1.4% and 1.8%.

“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,” said Troels Yndigegn, MD, the study’s lead author. “We believe that the evidence still supports beta-blockers for patients with a large myocardial infarction that experience heart failure, but for patients with no signs of heart failure and a normal ejection fraction, this trial establishes that there’s no indication that routine use of beta-blockers is beneficial.”

“A critical axiom in evidence-based medicine is that ‘absence of evidence is not evidence of absence,’” wrote Philippe Gabriel Steg, MD, FACC, in an accompanying editorial commentary.  “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. While we await the results of the multiple upcoming trials re-evaluating the role of beta-blockers in contemporary care, it may be prudent to place routine beta-blocker therapy after myocardial infarction on ‘injured reserve.’”