BACKGROUND AND AIMS: Recent trials have challenged the guideline recommendation of beta-blockers for post-myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF). Whether these recent findings apply equally to women and men remains unknown.
METHODS: Using data from REBOOT (tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion), the largest randomized trial evaluating the effect of beta-blockers after acute MI with LVEF > 40%, a pre-specified sex-specific subgroup analysis was performed. A total of 8438 out of the 8505 randomized patients comprised the intention-to-treat population.
RESULTS: Among 8438 patients, 1627 were women, who were older, had more comorbidities, and received fewer guideline-based therapies than men. Over a median follow-up of 3.7 years, women had overall higher rates of the primary composite outcome (death, MI, or heart failure hospitalization) than men. The incidence rate of the primary endpoint in women was 30.4 and 21.0/1000 patient-years in the beta-blocker group and no beta-blocker group, respectively (hazard ratio 1.45, 95% confidence interval 1.04-2.03). No significant differences were observed in men (hazard ratio .94, 95% confidence interval .79-1.13; P for interaction = .026). The excess risk in women was mainly 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).
CONCLUSIONS: In the REBOOT trial of MI patients managed according to contemporary standards, beta-blocker therapy was associated with evidence of harm in women-particularly those with preserved LVEF and receiving higher doses-an effect not observed in men.
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| Cardiology |
This is likely a chance finding that is essentially limited to a subgroup (those with LVEF >=50% but NOT <50%, and receiving higher doses), only for mortality (and not the other CV endpoints), and is not a particularly robust finding (overall small number of events). These findings are also in contrast with other beta-blocker trials showing no difference by sex. So, hypothesis-generating but not practice-changing.
Sex-specific effects of beta-blockers after myocardial infarction in patients without reduced left ventricular ejection fraction (LVEF =40) are presented. The main finding is that beta-blocker therapy was associated with harm in women, especially those with preserved LVEF and those receiving higher doses. This harmful effect was not observed in men. The study highlights important sex differences in response to beta-blockers post-MI and suggests the need for reconsidering beta-blocker use in women without reduced LVEF.
An important addition to the literature. As guidelines continue to evolve on using beta-blockers after MI, the REBOOT trial has a compelling suggestion that investigating sex-specific effects of medications is important and may yield additional secondary insights into management differences.
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