Beta-Blockers Linked to Worse Outcomes in Women Following a Heart Attack

Valentín Fuster, MD, PhD
Credit: Mount Sinai

Research from the European Society of Cardiology (ESC) Congress 2025 provides important new insight into the sex-specific outcomes following a heart attack, including the effect of beta-blockers.

The data, which were an analysis of the REBOOT clinical trial, suggest women experience worse outcomes than their male counterparts following a myocardial infarction (MI) and those treated with beta-blockers post-event had a greater risk of mortality, reinfarction, and hospitalization for heart failure compared to women not receiving the class of medication.^1,2

“We have been investigating sex-differences in cardiovascular disease for a long time. We already knew that cardiovascular disease presentation is different in women and men, and this study significantly adds to this knowledge by showing that response to medications is not necessarily equal in women and men,” said study investigator Valentín Fuster, MD, PhD, president of the Mount Sinai Foster Heart Hospital and at the Nacional de Investigaciones Cardiovasculares Carlos III (CNIC).² “This study should spark the much-needed sex-specific approach for cardiovascular disease”.

Initiated by investigators at the CNIC as a randomized, open-blinded endpoint trial, the REBOOT trial was launched in 2018 to explore the effect of beta-blocker therapy, a guideline-directed medical therapy in patients with heart failure with reduced ejection fraction, in patients with a MI and who had a left ventricular ejection fraction (LVEF) of at least 40% or more. Presented at ESC Congress 2025 and simultaneously published in the New England Journal of Medicine, the overall trial concluded there was no evidence of an effect on all-cause death, reinfarction or heart failure admission, with events occurring among 316 patients in the beta-blocker group and in 307 patients in the no beta-blocker group (hazard ratio (HR), 1.04; 95% confidence interval [CI], 0.89 to 1.22; P = .63).³

In addition to primary results, investigators presented a post hoc analysis at ESC Congress 2025 examining sex-specific differences in the trial.¹

Of the 8438 patients included in the intention-to-treat population, 1627 were women. Results suggested women in the trial were older, had more comorbidities, and received fewer guideline-based therapies than men.¹

During a median follow-up of 3.7 years, women had overall higher rates of the primary composite outcome than men, with an incidence rate in women of 30.4 per 1000 patient-years in the beta-blocker group and 21.0 per 1000 patient-years in the no beta-blocker group (HR, 1.45; 95% CI, 1.04 to 2.03). In contrast, no significant differences were observed among men included in the trial (HR, 0.94; 95% CI, 0.79 to 1.13; P for interaction = .026).¹

Further analysis demonstrated the excess risk observed in women was primarily driven by increased mortality and was most evident among those with preserved LVEF (P for interaction = .030) and those receiving higher beta-blocker doses (P for interaction = .045).¹

"Our findings suggest that a one-size-fits-all approach may not be appropriate and that sex-specific considerations are crucial for cardiovascular interventions prescriptions,” said study investigator Xavier Rosselló, MD, PhD, a scientist at CNIC and a cardiologist at University Hospital Son Espases in Mallorca.²

References:

1. Rosello X, Dominguez-Rodriguez A, Latini R. Beta-blockers after myocardial infarction: effects according to sex in the REBOOT trial. European Heart Journal. Published online August 30, 2025. doi: 10.1093/eurheartj/ehaf673

2. Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.). New study finds that, after a heart attack, women have worse prognosis when treated with beta-blockers. EurekAlert! Published August 30, 2025. Accessed August 31, 2025. https://www.eurekalert.org/news-releases/1096049

3. Ibanez B, Latini R, Rossello X, et al. Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction. New England Journal of Medicine. Published online August 30, 2025. doi: 10.1056/nejmoa2504735