For at least a quarter of a century, the initiation of beta-blockers for secondary prevention of cardiovascular disease (CVD) in patients after myocardial infarction (MI) or acute coronary syndrome (ACS) has been the unquestioned standard of care.

Until now.

 

Surprising findings

 

The REDUCE-AMI trial was a parallel-group, open-label trial of 5,020 patients, performed at centers in New Zealand, Sweden, and Estonia.

Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. 2024;390:1372–1381.

Patients with acute MI who had undergone coronary angiography and maintained a left ventricular ejection fraction (LVEF) of at least 50% were randomized to receive either long-term treatment with metoprolol or bisoprolol, or no beta-blocker treatment.

 

The primary endpoint was a composite of all-cause death or recurrent MI over a median follow-up of 3.5 years.

Death from any cause occurred in 3.9% of patients receiving beta-blockers and 4.1% of patients in the no-beta-blocker group; respective results for other endpoints were death from cardiovascular causes, 1.5% and 1.3%; hospitalization for heart failure, 0.8% and 0.9%; myocardial infarction, 4.5% and 4.7%; and hospitalization for atrial fibrillation, 1.1% and 1.4%.

Hospitalization for safety endpoints of bradycardia, atrioventricular block, syncope, hypotension, or pacemaker implantation occurred in 3.4% of patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group.

From these findings, the study authors concluded: “Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved [LVEF] (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use.”

 

Why the change?

 

As the researchers note, the majority of clinical trials that have shown benefit from beta-blocker treatment post-MI included patients with large infarct territories and were conducted years ago—that is, in an era “before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists.”

It is also important to note that this study was limited to patients with preserved ejection fraction, and the use of beta-blockers such as carvedilol in patients with reduced ejection fraction or other cardiomyopathies has not yet been challenged.

 

Reflections from an expert

 

As a preventive cardiologist whose entire career has been focused on primary, secondary, and tertiary prevention of CVD, I have embraced the use of beta-blockers as a mainstay of therapy in my patients with established CAD, regardless of ejection fraction. However, this new trial provides compelling evidence for a reconsideration. 

Against our current backdrop of more-effective therapies and a change in general patient presentation (particularly from larger to smaller MIs at presentation), beta-blockers may no longer be necessary or even beneficial for secondary prevention and beyond in patients with preserved LVEF.

The impact of these new findings is likely to be quite similar to what we have seen—and continue to see—regarding the diminishing benefit of aspirin for CVD prevention,

Murphy E, Curneen JMG, McEvoy JW. Aspirin in the modern era of cardiovascular disease prevention. Methodist Debakey Cardiovasc J. 2021;17(4):36–47.

and for similar reasons: Advances in CVD treatment and prevention are making the old ways obsolete.