Decades of Beta Blocker Use Questioned as Major Study Shows No Benefit
The REBOOT trial found no benefit of beta blockers after heart attack in patients with preserved heart function.
Decades after beta blockers became standard therapy following heart attacks, new research is challenging their routine use.
Conducted across 109 hospitals in Spain and Italy and published in The New England Journal of Medicine, the REBOOT trial found no benefit of beta blockers in patients with preserved or mildly reduced heart function.
A substudy also revealed potential sex-specific differences, with women experiencing higher risks of hospitalization for heart failure, particularly at higher beta blocker doses.
How beta blockers became standard post-heart attack therapy
Beta blockers have been prescribed after heart attacks for many years, but their role in modern care is being reconsidered. Early clinical trials in the 1970s and 1980s showed the drugs reduced mortality by lowering heart rate and preventing arrhythmias.
However, those findings were made in a different era of cardiology. At that time, patients often received limited treatment beyond supportive care. Modern treatments such as stenting, dual antiplatelet therapy and high-intensity statins have reduced heart damage and complications.
Despite this shift, international guidelines have continued to recommend beta blockers after myocardial infarction, even for patients with preserved heart function. Observational studies and meta-analyses have produced inconsistent results. More recently, the REDUCE-AMI trial in 2024, which included patients with a left ventricular ejection fraction (LVEF) >50%, reported no reduction in death or recurrent heart attack with beta blockers. However, that study excluded patients with mildly reduced heart function, leaving uncertainty for this broader group.
Left ventricular ejection fraction (LVEF)
The percentage of blood pumped out of the left ventricle with each heartbeat; used to measure heart function.
“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,” said lead author Dr. Borja Ibáñez, the director of Clinical Research of the National Center for Cardiovascular Research.
“While we often test new drugs, it's much less common to rigorously question the continued need for older treatments,” said Ibáñez.
The REBOOT trial was designed to address this question directly: do beta blockers provide benefit in patients with myocardial infarction and preserved or mildly reduced LVEF in the setting of contemporary care? A pre-specified substudy also examined differences between men and women, a long-neglected area in cardiovascular research.
The REBOOT trial and its findings on beta blockers
The REBOOT trial was a randomized, open-label study that enrolled patients across 109 hospitals in Spain and Italy. A total of 8,438 participants were included, 19% of whom were women. All had experienced a heart attack, had a LVEF >40% and showed no signs of heart failure.
Patients were randomly assigned at discharge to begin a beta blocker or to forgo the medication. They were otherwise treated with current standard therapies, including statins and dual antiplatelet drugs. Follow-up continued for a median of 3.7 years, and the primary outcome was a combined measure of all-cause death, another heart attack or hospitalization for heart failure.
“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,” said Ibáñez.
The main results showed no difference between groups. The primary outcome occurred at similar rates, with a hazard ratio of 1.04. When the three components were examined individually – death, reinfarction or hospitalization for heart failure – none showed significant differences. Although safety outcomes also did not differ, suggesting no hidden benefit or harm from routine beta blocker use.
Hazard ratio
A measure used in clinical trials to compare the risk of a specific event happening in one group versus another over time.
In the substudy, among the 1,627 women enrolled, event rates were higher than in men. Women who received beta blockers had worse outcomes, with a hazard ratio of 1.45. Women on higher beta blocker doses experienced the greatest increase in risk, particularly for mortality. By contrast, the 6,811 men showed no evidence of harm or benefit, with a hazard ratio of 0.94.
Implications of REBOOT for beta blocker prescriptions
The REBOOT findings suggest that, for patients with an uncomplicated heart attack and preserved heart function, beta blockers may no longer be needed. If incorporated into practice, these results could drive a major shift in international guidelines. Reducing unnecessary prescriptions also means fewer side effects such as fatigue, low heart rate and sexual dysfunction.
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“Currently, more than 80% 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,” said Ibáñez.
However, for the first time, a large randomized trial points to possible harm in women.
Although there are limits to what REBOOT can answer. The trial was not powered to test sex differences, meaning those results remain exploratory. Its conclusions apply only to patients with preserved or mildly reduced ejection fraction.
Evidence also remains strong that patients with reduced function (40% or less) still benefit from beta blockers.
Future studies are needed to confirm these sex-specific findings and guide more personalized post-heart attack care.
References:
1. Ibanez B, Latini R, Rossello X, et al. Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction. N Engl J Med. 2025:NEJMoa2504735. doi: 10.1056/NEJMoa2504735
2. Rossello X, Dominguez-Rodriguez A, Latini R, et al. Beta-blockers after myocardial infarction: effects according to sex in the REBOOT trial. Eur Heart J. 2025:ehaf673. doi: 10.1093/eurheartj/ehaf673
This article is a rework of a press release issued by Mount Sinai. Material has been edited for length and content.
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