Women Face Worse Outcomes Post-Heart Attack When Treated with Beta-Blockers, New Study Finds

A groundbreaking analysis from the REBOOT (Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction) clinical trial has highlighted significant sex-specific differences in the effects of beta-blocker therapy following a heart attack. Conducted and coordinated by the Centro Nacional de Investigaciones Cardiovasculares (CNIC), this extensive international study, recently published in the European Heart Journal, raises important questions about the universality of current post-heart attack treatments.

REBOOT is the largest trial to date examining the impact of beta-blockers in patients who survive a myocardial infarction (heart attack) without substantial deterioration in cardiac function. Specifically, it included 8,505 patients from 109 hospitals across Spain and Italy, focusing on individuals with a left ventricular ejection fraction greater than 40%. While women represented a smaller proportion of the trial population—a common trend in cardiovascular research—they accounted for the largest number of women ever enrolled in a beta-blocker post-infarction study, providing valuable insights.

Participants were randomly assigned to receive either beta-blockers, a widely prescribed medication for heart attack recovery, or no beta-blockers, alongside standard care. The follow-up period averaged nearly four years. The findings revealed notable sex differences: men did not experience significant benefits or risks from beta-blocker treatment, whereas women treated with beta-blockers faced a markedly increased risk of death, reinfarction, or hospitalization for heart failure compared to women who did not receive the medication.

Specifically, women on beta-blockers had a 2.7% higher absolute risk of mortality over the median follow-up of 3.7 years. The increased risk was particularly evident in women with fully normal cardiac function, indicated by a left ventricular ejection fraction of 50% or higher. In these cases, beta-blockers appeared to do more harm than good. Conversely, women with mild cardiac deterioration did not show the same elevated risk.

Additional analysis showed that women with infarctions often presented with a more complex cardiovascular profile despite overall worse outcomes. They were generally older, with higher incidences of hypertension, diabetes, and dyslipidemia, and more frequently experienced infarctions without obstructive coronary arteries (6% in women vs. 2% in men). Furthermore, women were less likely than men to receive some guideline-recommended therapies, including antiplatelets, statins, ACE inhibitors, ARBs, or participation in cardiac rehabilitation.

The study also confirmed that women had a worse overall prognosis than men, with a mortality rate of 4.3% compared to 3.6% in men during the study period. Leading the research, Dr. Borja Ibáñez emphasized that these findings reinforce previous observational data, demonstrating that women with infarctions tend to have a worse cardiovascular profile and prognosis. Crucially, the response to beta-blocker treatment differs by sex, underscoring the need for personalized therapy.

Cardiologist Xavier Rosselló highlighted the importance of considering sex differences in treatment decisions, suggesting that a one-size-fits-all approach may be ineffective or even harmful. The trial's insights imply that clinicians should carefully evaluate the risks and benefits of beta-blocker therapy in women after an uncomplicated heart attack, potentially adjusting doses or exploring alternative treatments.

The REBOOT trial's comprehensive data underscore a vital shift towards personalized medicine in cardiology. Tailoring treatments based on sex and individual patient profiles could significantly improve outcomes and reduce adverse effects for women. Dr. Valentín Fuster, CNIC General Director, emphasized the importance of recognizing these sex-based differences, stating that this study adds a crucial piece to understanding how cardiovascular responses vary between men and women and calls for a sex-specific approach to cardiovascular care.

Published by the CNIC in collaboration with the Mario Negri Institute in Italy, the REBOOT trial provides robust evidence that could influence future guidelines, promoting safer and more effective treatment strategies tailored to each patient's unique profile.