The findings come from the REBOOT Trial, a large international study led by senior investigator Valentin Fuster, MD, PhD, President of Mount Sinai Fuster Heart Hospital and General Director of Spain’s Centro Nacional de Investigaciones Cardiovasculares (CNIC). Results were presented during a “Hot Line” session at the European Society of Cardiology Congress in Madrid and published in The New England Journal of Medicine.

A 40-Year Standard Is Challenged

Beta blockers became standard after heart attacks at a time when modern cardiac care looked very different. Today, blocked coronary arteries are often reopened quickly, and patients also receive powerful therapies such as statins, antiplatelet drugs, and other evidence-based treatments. That shift has raised a major question: do beta blockers still add meaningful protection for patients whose hearts are pumping normally after an uncomplicated heart attack?

REBOOT tested that question directly. Researchers enrolled 8,505 patients from 109 hospitals in Spain and Italy. After leaving the hospital, participants were randomly assigned to receive beta blockers or to avoid them. Everyone otherwise received current standard care, and researchers followed them for a median of almost four years.

The result was striking: beta blockers did not significantly reduce death, repeat heart attack, or hospitalization for heart failure in patients whose heart function was preserved. For a drug given so routinely for so long, that lack of benefit could have major implications.

“This trial will reshape all international clinical guidelines. It joins other previous landmark trials led by CNIC and Mount Sinai — such as SECURE with the polypill and DapaTAVI, with SLT2 inhibition associated to TAVI — that have already transformed some global approaches to cardiovascular disease,” says Dr. Fuster.

Why the Finding Matters

According to the investigators, more than 80 percent of patients with uncomplicated myocardial infarction are currently sent home on beta blockers. If many of these patients do not actually benefit, doctors could eventually reduce unnecessary medication use, limit side effects, and make recovery regimens easier to follow.

“REBOOT will change clinical practice worldwide,” says Principal Investigator Borja Ibáñez, MD, CNIC’s Scientific Director, who presented the results. “Currently, more than 80 percent of patients with uncomplicated myocardial infarction are discharged on beta blockers. The REBOOT findings represent one of the most significant advances in heart attack treatment in decades.”

Although beta blockers are generally considered safe, they can cause fatigue, bradycardia (low heart rate), and sexual dysfunction. For patients already taking multiple drugs after a heart attack, removing an unhelpful medication could make treatment simpler and improve quality of life.

Concerning Signal in Women

A REBOOT substudy published in the European Heart Journal added another important layer. Women who received beta blockers had a higher risk of death, heart attack, or hospitalization for heart failure compared with women who did not receive the drugs. The same increased risk was not seen in men.

The sex-specific finding was especially notable among women whose heart function was completely normal after a heart attack, defined as a left ventricular ejection fraction of 50 percent or higher. In that group, women treated with beta blockers had a 2.7 percent higher absolute risk of mortality during 3.7 years of follow-up compared with women who were not treated with beta blockers. Women with mildly reduced cardiac function did not show the same excess risk.

The finding does not mean patients should stop taking prescribed medication on their own. It does suggest that one-size-fits-all prescribing after heart attack may need to give way to more personalized decisions, especially for patients with preserved heart function.

Modern Treatment Has Changed the Equation

“After a heart attack, patients are typically prescribed multiple medications, which can make adherence difficult,” explains Dr. Ibáñez. “Beta blockers were added to standard treatment early on because they significantly reduced mortality at the time. Their benefits were linked to reduced cardiac oxygen demand and arrhythmia prevention. But therapies have evolved. Today, occluded coronary arteries are reopened rapidly and systematically, drastically lowering the risk of serious complications such as arrhythmias. In this new context — where the extent of heart damage is smaller — the need for beta blockers is unclear. While we often test new drugs, it’s much less common to rigorously question the continued need for older treatments.”

That was the central motivation behind REBOOT: to test whether an old standard still makes sense in the era of rapid artery reopening and modern prevention.

“The trial was designed to optimize heart attack care based on solid scientific evidence and without commercial interests. These results will help streamline treatment, reduce side effects, and improve quality of life for thousands of patients every year,” Dr. Ibanez adds.

REBOOT was conducted without pharmaceutical industry funding.

Other Major Trials Add Nuance

REBOOT is not the only recent study to question routine beta blocker use after heart attack. The REDUCE-AMI trial, published in 2024, also found no significant reduction in death or another heart attack among patients with preserved heart function who received beta blockers after myocardial infarction.

However, the picture is not identical for all patients. The BETAMI-DANBLOCK trials, also presented at the European Society of Cardiology Congress in 2025, found that beta blockers reduced a combined measure of death and major cardiovascular events in selected heart attack patients with preserved or mildly reduced heart function.

A later individual patient data meta-analysis helped clarify the difference. For patients with normal heart function, defined as a left ventricular ejection fraction of at least 50 percent, beta blockers did not reduce death, heart attack, or heart failure after myocardial infarction. But separate pooled data suggested that patients with mildly reduced heart function, with a left ventricular ejection fraction of 40 to 49 percent, may still benefit.

Toward More Personalized Heart Attack Care

Together, the evidence points toward a more selective future for beta blockers after heart attack. They remain important for many patients, especially those with reduced heart function or other medical reasons to take them. But for patients who recover from an uncomplicated heart attack with normal pumping function, the routine prescription of beta blockers is now under serious scrutiny.

The shift fits a broader movement in heart care: not simply adding more medications, but asking which treatments still matter most for today’s patients. For millions of heart attack survivors, that could eventually mean fewer pills, fewer side effects, and a recovery plan built more carefully around individual risk.