Article Impact Level: HIGH Data Quality: STRONG Summary of European Heart Journal, ehaf673. https://doi.org/10.1093/eurheartj/ehaf673 Dr. Xavier Rossello et al.
Points
- The REBOOT trial found that beta-blockers increased the risk of adverse outcomes in women post-myocardial infarction with preserved ejection fraction, an effect not seen in men.
- Women receiving beta-blockers had a 45% higher relative risk of the primary composite outcome and a 2.7% higher absolute mortality risk over a 3.7-year follow-up period.
- This elevated risk was most pronounced in women with a left ventricular ejection fraction of 50% or higher and in those who were receiving higher doses of beta-blockers.
- Compared to men, female participants in the trial were older, had more comorbidities, and were less likely to receive other guideline-recommended therapies for secondary prevention after their heart attack.
- These findings suggest a personalized, sex-specific approach is crucial for post-myocardial infarction care, as a one-size-fits-all beta-blocker prescription may cause harm in certain female patients.
Summary
A pre-specified sex-specific subgroup analysis of the REBOOT trial evaluated beta-blocker therapy in 8438 post-myocardial infarction (MI) patients with a left ventricular ejection fraction (LVEF) > 40%. The intention-to-treat population included 1627 women, who were older and had more comorbidities than the male participants. Over a median follow-up of 3.7 years, women had a higher overall rate of the primary composite outcome, which included death, MI, or heart failure hospitalization. This analysis revealed a significant interaction between sex and treatment effect (P for interaction = .026), indicating a differential response to beta-blockers.
For women, beta-blocker therapy was associated with a significantly increased risk of the primary endpoint, with an incidence rate of 30.4/1000 patient-years, compared to 21.0/1000 patient-years in the no beta-blocker group (hazard ratio, 1.45; 95% confidence interval, 1.04–2.03). In contrast, no significant difference was observed in men (hazard ratio, 0.94; 95% confidence interval, 0.79–1.13). An increase in mortality primarily drove the excess risk in women, corresponding to a 2.7% higher absolute risk of mortality over the study period.
The detrimental effect in women was most evident among those with a preserved LVEF of 50% or higher (P for interaction = .030) and those receiving higher beta-blocker doses (P for interaction = .045). Baseline data also showed women were less likely to receive other guideline-recommended therapies and had a worse overall prognosis (4.3% mortality vs. 3.6% in men). These findings from the largest randomized trial on this topic suggest that beta-blocker therapy may be harmful in women after MI without reduced LVEF, underscoring the need for a sex-specific approach to post-MI care.
Link to the article: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf673/8243876
References Rossello, X., Dominguez-Rodriguez, A., Latini, R., Sánchez, P. L., Raposeiras-Roubín, S., Anguita, M., Barrabés, J. A., Grigis, G., Owen, R., Pocock, S., Gómez-Talavera, S., García-Lunar, I., Escalera, N., Pérez-García, C. N., Di Fusco, S. A., Pizarro, G., López Benito, M., Pongetti, G., Rincón-Díaz, L. M., … Ibanez, B. (2025). Beta-blockers after myocardial infarction: Effects according to sex in the REBOOT trial. European Heart Journal, ehaf673. https://doi.org/10.1093/eurheartj/ehaf673
