For decades, beta blockers have been one of the routine medications taken by many patients after a heart attack. They are widely used in heart disease and have long been considered a standard part of recovery after myocardial infarction. But a major clinical trial in 2025 suggests that many people with good heart function who have uncomplicated heart attacks may not benefit at all from taking these drugs.
The findings come from the REBOOT trial, a large international study led by senior investigator Valentin Faster, MD, director of Mount Sinai Faster Heart Hospital and executive director of Spain’s Center for Cardiovascular Investigation (CNIC). The results were presented at the European Society of Cardiology’s ‘Hotline’ session in Madrid. New England Medical Journal.
40 years of challenging standards
At a time when modern heart care was very different, beta-blockers became standard after a heart attack. Now, blocked coronary arteries often reopen quickly, and patients also receive intensive treatments such as statins, antiplatelet drugs, and other evidence-based treatments. This change raised a big question: Do beta-blockers still offer meaningful protection for patients whose hearts are beating normally after an uncomplicated heart attack?
REBOOT tested that question directly. Researchers enrolled 8,505 patients from 109 hospitals in Spain and Italy. After discharge, participants were randomly assigned to receive beta-blockers or avoid beta-blockers. All others otherwise received the current standard of care, and the researchers followed them for a median of nearly four years.
The results were amazing. Beta-blockers did not significantly reduce death, repeated heart attacks, or hospitalization for heart failure in patients with preserved heart function. For drugs that are routinely administered for very long periods of time, their lack of efficacy can have major implications.
“This trial will reshape all international clinical guidelines. It joins previous landmark trials led by CNIC and Mount Sinai, such as SECURE with the polypill and DapaTAVI with TAVI-related SLT2 inhibition, which are already transforming some of the global approaches to cardiovascular disease,” said Dr. Faster.
Why the findings matter
More than 80% of patients with uncomplicated myocardial infarction are now sent home on beta-blockers, according to researchers. If many of these patients do not actually benefit, doctors may ultimately be able to reduce unnecessary drug use, limit side effects, and make it easier to follow a recovery plan.
“REBOOT will change clinical practice around the world,” said Borja Ibáñez, MD, CNIC’s scientific director and principal investigator, who announced the results. “More than 80 percent of patients with uncomplicated myocardial infarction are now discharged from the hospital on beta-blockers. The REBOOT study results represent one of the most important advances in heart attack treatment in recent decades.”
Although beta blockers are generally considered safe, they can cause fatigue, bradycardia (slow heart rate), and sexual dysfunction. For patients who are already taking multiple medications after a heart attack, removing unhelpful medications can simplify treatment and improve quality of life.
About female signals
The REBOOT substudy is european heart journal Another important layer has been added. Women who received beta-blockers had a higher risk of death, heart attack, or hospitalization for heart failure than women who did not receive beta-blockers. A similar increased risk was not seen in men.
This sex-specific finding was particularly pronounced in women whose heart function was completely normal (defined as a left ventricular ejection fraction of 50 percent or higher) after the heart attack. In that group, women treated with beta-blockers had a 2.7 percent higher absolute risk of death during 3.7 years of follow-up compared with women who were not treated with beta-blockers. Women with mildly impaired cardiac function did not show a similar excess risk.
This finding does not mean patients should stop taking prescription drugs on their own. This suggests that one-size-fits-all prescriptions after a heart attack may need to be replaced by more individualized decisions, especially for patients with preserved heart function.
Modern treatments have changed the equation
“After a heart attack, patients are usually prescribed multiple medications, which can make compliance difficult,” Dr. Ibáñez explains. “Beta-blockers were added to the standard of care early on because they significantly reduced mortality rates at the time. Their benefits were associated with lowering the heart’s oxygen demand and preventing arrhythmias. However, treatments have evolved. Now, occluded coronary arteries can be rapidly and systematically recanalized to prevent arrhythmias, etc. The risk of serious complications is significantly lower. In this new situation where the extent of cardiac damage is smaller, the need for beta-blockers is unclear. We frequently test new drugs, but it is much less common to severely question the continued need for older treatments. ”
That was the core motivation behind REBOOT. That is, to test whether old standards still make sense in the era of rapid arterial recanalization and modern prevention.
“This trial was designed to optimize heart attack treatment without commercial interest and based on solid scientific evidence. These results will help streamline treatment, reduce side effects, and improve the quality of life for thousands of patients each year,” Dr. Ibanez added.
REBOOT was carried out without funding from the pharmaceutical industry.
Other major trials add nuance
REBOOT is not the only recent study to question the routine use of beta-blockers after a heart attack. The REDUCE-AMI trial, published in 2024, also found no significant reduction in death or another heart attack in patients with preserved heart function who received beta-blockers after a myocardial infarction.
However, the situation is not the same for all patients. The BETAMI-DANBLOCK trial, also presented at the 2025 European Congress of Cardiology, found that beta-blockers reduced a composite measure of death and major cardiovascular events in selected heart attack patients with preserved or mildly impaired heart function.
A subsequent meta-analysis of individual patient data clarified the differences. For patients with normal heart function, defined as a left ventricular ejection fraction of at least 50 percent, beta-blockers did not reduce death after myocardial infarction, heart attack, or heart failure. However, separate pooled data suggest that patients with left ventricular ejection fractions of 40 to 49 percent and mildly decreased heart function may still benefit.
Aiming for more personalized heart attack treatment
Taken together, these evidences point to a future in which beta-blockers become more selective after heart attack. They remain important for many patients, especially those with compromised heart function or those taking them for other medical reasons. But the routine prescription of beta-blockers for patients who recover from an uncomplicated heart attack with normal pump function is now under intense scrutiny.
This change fits into a broader movement in cardiac care that goes beyond simply adding more drugs and asks which treatments are still most important for today’s patients. For millions of heart attack survivors, that could ultimately mean lower doses of medication, fewer side effects, and a more carefully constructed recovery plan based on individual risk.
