Key Findings from the REBOOT Trial

A comprehensive analysis from the REBOOT (Treatment with Beta-blockers after Myocardial Infarction without Reduced Ejection Fraction) clinical trial has unveiled significant sex-based differences in outcomes for women treated with beta-blockers following heart attacks. Conducted by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and published in the European Heart Journal, this study raises critical questions about existing treatment protocols.

The REBOOT trial, the largest contemporary study examining the effects of beta-blockers on patients who survive myocardial infarction with preserved cardiac function, included 8,505 participants across 109 hospitals in Spain and Italy. While the proportion of women involved was relatively low, it marked the largest number of female subjects in such trials to date, lending robust statistical power to the findings.

Trial Methodology and Results

Participants were randomly assigned to either receive beta-blockers, a commonly prescribed medication post-heart attack, or to forego this treatment while continuing standard care. Over a median follow-up period of nearly four years, the results revealed stark differences between the sexes. Men showed no significant benefits or risks associated with beta-blocker therapy, whereas women treated with these medications exhibited a notably higher risk of mortality, reinfarction, or hospitalization due to heart failure compared to their counterparts who did not receive the drug.

Specifically, women on beta-blockers had a 2.7% higher absolute risk of death throughout the study's duration, particularly those with normal cardiac function post-infarction (left ventricular ejection fraction of 50% or higher). In contrast, women who experienced only mild deterioration in heart function did not face an increased risk from beta-blocker treatment.

Gender Disparities in Heart Health

The analysis also highlighted that women presenting with myocardial infarctions had a more severe cardiovascular profile, often being older and having a higher prevalence of comorbid conditions such as hypertension, diabetes, and dyslipidemia. Furthermore, women were more likely to experience heart attacks without obstructive coronary arteries compared to men (6% vs. 2%).

Despite high overall prescription rates for secondary prevention therapies among trial participants, women were less frequently administered some guideline-recommended treatments, including antiplatelets, statins, angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARBs), and cardiac rehabilitation programs. Throughout the study, women faced a significantly worse prognosis than men, with mortality rates of 4.3% for women compared to 3.6% for men.

Implications for Clinical Practice

The principal investigator of the REBOOT trial emphasized the study's confirmation of previous observational data regarding the poorer cardiovascular outcomes for women following heart attacks. The results call into question the traditional one-size-fits-all approach to treatment and underscore the necessity for sex-specific considerations in prescribing cardiovascular interventions.

The collaboration between the CNIC and the Mario Negri Institute for Pharmacological Research in Milan, Italy, has yielded crucial insights into the personalized treatment of heart attack survivors. Experts involved in the research suggest that the routine prescription of beta-blockers for women post-heart attack may be counterproductive, advocating for a careful evaluation of risks and benefits, as well as potential adjustments in dosing or consideration of alternative therapies.

These findings highlight the importance of tailoring post-heart attack treatment to individual patient profiles, particularly factoring in gender differences, to improve health outcomes for women globally.