Beta-blockers after myocardial infarction without reduced ejection fraction: no benefit in REBOOT trial

The role of beta-blockers after myocardial infarction (MI) has been debated in the contemporary era of routine reperfusion, revascularization, and optimal pharmacotherapy. While early trials in the pre-reperfusion era suggested a 23% reduction in mortality, more recent observational studies and meta-analyses have yielded heterogeneous results, particularly for patients with preserved or mildly reduced left ventricular ejection fraction (LVEF).

The REBOOT trial (Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction), a pragmatic, open-label, randomized study with blinded endpoint adjudication, enrolled 8,438 patients across 109 centers in Spain and Italy. Eligible patients had ST-elevation or non–ST-elevation MI, underwent invasive care, and had LVEF >40% at discharge. Participants were randomized to receive beta-blocker therapy (bisoprolol in 85.9% of cases, with smaller numbers receiving metoprolol, carvedilol, or nebivolol) or no beta-blocker, with a median follow-up of 3.7 years.

The primary endpoint, a composite of all-cause death, reinfarction, or hospitalization for heart failure, occurred in 316 patients (22.5/1000 patient-years) in the beta-blocker arm and 307 (21.7/1000 patient-years) in the control arm (HR 1.04; 95% CI 0.89–1.22; P=0.63). Secondary outcomes, including all-cause death (HR 1.06), reinfarction (HR 1.01), and HF hospitalization (HR 0.89), also showed no significant differences.

Safety outcomes were comparable, with no excess in advanced atrioventricular block or arrhythmic events. Subgroup analyses suggested possible heterogeneity by sex (higher event rates in women on beta-blockers) and infarct type (higher events in STEMI patients on beta-blockers), but these were exploratory and hypothesis-generating.

These results align with the REDUCE-AMI and CAPITAL-RCT trials and reinforce recent meta-analyses showing no clear long-term benefit of beta-blockers after MI when LVEF is preserved. Notably, current guidelines (ACC/AHA 2025 and ESC 2023) still recommend beta-blockers post-MI regardless of EF, but the present findings may prompt reconsideration, particularly for uncomplicated patients with LVEF >40%.

#MyocardialInfarction #BetaBlockers #Cardiology #REBOOTTrial #NEJM

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