A major international clinical trial has overturned four decades of standard cardiac care, finding that beta-blockers provide no benefit for most heart attack survivors with preserved heart function. The REBOOT study, involving over 8,500 patients, could reshape treatment guidelines worldwide.
The REBOOT clinical trial has delivered a seismic shift to cardiovascular medicine, challenging one of its most entrenched treatment paradigms. This landmark study, coordinated by Spain’s Centro Nacional de Investigaciones Cardiovasculares (CNIC), found that beta-blockers – routinely prescribed to heart attack patients for over 40 years – offer no clinical benefit for those with uncomplicated myocardial infarction.
The findings, published simultaneously in The New England Journal of Medicine and The Lancet on 30 August 2025, emerged from the largest trial ever conducted on this question. Researchers enrolled 8,505 patients across 109 hospitals in Spain and Italy, following them for nearly four years after their heart attacks.
Most patients show no benefit from standard treatment
The trial focused on patients whose heart attacks left their cardiac function relatively intact – specifically those with left ventricular ejection fractions above 40%. This represents the vast majority of modern heart attack survivors, as improved emergency cardiac care means approximately 70% now survive with preserved heart function.
“REBOOT will change clinical practice worldwide,” said principal investigator Dr Borja Ibáñez, CNIC Scientific Director and cardiologist at Hospital Universitario Fundación Jiménez Díaz. “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.”
The study revealed no significant differences between patients who received beta-blockers and those who didn’t in rates of death, recurrent heart attack, or hospitalisation for heart failure. This null result challenges decades of clinical practice based on earlier studies conducted when cardiac care was less advanced.
Subgroup analysis reveals crucial distinctions
However, the research uncovered important nuances through detailed subgroup analysis. While patients with fully preserved heart function (ejection fraction above 50%) showed no benefit from beta-blockers, those with moderately reduced function (40-50%) appeared to derive some advantage.
To investigate this finding further, the researchers conducted a meta-analysis with other trials, published in The Lancet. This confirmed that beta-blockers significantly reduce risks of death, recurrent heart attack, or heart failure only in patients with moderately reduced cardiac contractile function.
“Taken together, these two studies provide compelling evidence that post-infarction patients with fully preserved contractile function do not benefit from beta-blockers, whereas those with moderate or greater dysfunction do,” explained Dr Xavier Rosselló, CNIC scientist and cardiologist at University Hospital Son Espases in Mallorca.
Clinical context drives paradigm shift
The timing of this research reflects fundamental changes in cardiac care since beta-blockers first showed benefit in the 1980s. Modern treatment involves systematic, rapid reopening of blocked coronary arteries, dramatically reducing complications like dangerous heart rhythms that beta-blockers were originally intended to prevent.
“Today, occluded coronary arteries are systematically reopened rapidly, drastically lowering the risk of serious complications such as arrhythmias,” noted Dr Ibáñez. “In this new context, where the extent of heart damage is smaller, the need for beta-blockers is unclear.”
The implications extend beyond efficacy to patient quality of life. Beta-blockers, whilst generally safe, can cause side effects including fatigue, bradycardia, and sexual dysfunction. Eliminating unnecessary prescriptions could improve patient adherence to essential medications whilst reducing adverse effects.
European research collaboration sets new standards
REBOOT demonstrated the power of academic-led research free from commercial influence. More than 500 researchers from Spain and Italy participated voluntarily, with the study funded entirely by public institutions including CNIC, the Spanish Society of Cardiology, and CIBERCV.
“The trial was designed to optimise heart attack care based on solid scientific evidence and without commercial bias,” emphasised Dr Ibanez. “These results will help simplify and streamline treatment, reduce adverse effects, and improve the quality of life for thousands of patients every year.”
The research affects millions of patients annually. More than two million Europeans suffer heart attacks each year, including around 70,000 in Spain alone. Until now, the majority were discharged with beta-blocker prescriptions – a practice now fundamentally questioned.
Dr Valentin Fuster, CNIC General Director and senior REBOOT investigator, placed the findings in broader context: “This trial will reshape all international clinical guidelines. It joins other land, mark trials led by CNIC that have already transformed the global approach to cardiovascular disease.”
Reference:
REBOOT Trial Investigators. (2025). Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction. The New England Journal of Medicine.
doi: https://doi.org/10.1056/NEJMoa2504735
