Women Face 45% Higher Mortality Risk From Beta-Blockers After Heart Attack

Women treated with beta-blockers (β-blockers) for post-myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF) have a 45% increased risk of MI, heart failure hospitalization, or death compared with men, according to new study findings. The results, published in the European Heart Journal, suggest a need to re-evaluate β-blocker use in post-MI women without reduced LVEF, with a view toward more sex-specific prescribing strategies.¹

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“Despite the underlying reasons not being fully understood, it is well established that women and men do not receive equal management—including pharmacological therapies—following an ACS [acute coronary syndrome],” the authors discussed. “Moreover, although findings vary across studies, several reports suggest that women may experience worse long-term outcomes than men after ACS."¹

Cardiovascular disease (CVD) affects nearly 60 million women in the United States alone, and only 44% see it as a significant health threat for women. This is largely in response to the prioritization of male enrollment in CVD clinical trials due to dissimilarities in women’s and men’s hormones, platelet reactivity, P2Y12 inhibitors, and the likelihood of developing comorbidities, which greatly impact responses to treatment. Continued evidence shows that women with cardiovascular conditions have increased adverse responses to cardiovascular drugs compared with men, with a risk that is 1.5 to 1.7 times higher. This underscores the critical need for inclusion of women in cardiovascular trials, as well as sex-based treatment guidelines.²

The authors assessed a pre-specified sex-specific subgroup analysis of REBOOT (NCT03596385), the largest randomized trial evaluating the effect of beta-blockers after acute MI with LVEF less than 40%. The assessment included a total of 8438 patients, of whom 1627 were older, had more comorbidities, and received fewer guideline-based therapies than men.^1,3

Over nearly 4 years of follow-up, women who had a heart attack were more likely than men to experience serious health problems such as death, another heart attack, or hospitalization for heart failure. Among women, these events happened more often in those who were taking beta-blockers compared with those who were not (about 30 vs 21 cases per 1,000 patients each year). This means women on beta-blockers had about a 45% higher risk of adverse events.¹

For men, there was no meaningful difference between taking beta-blockers or not. The higher risk seen in women was mostly due to increased deaths, and it was especially noticeable in women who had normal heart pumping function and in those who received higher doses of beta-blockers.¹

“Despite women and men differing with respect to baseline risk, causes, and prognosis of MI, current guidelines do not differentiate between the use of beta-blockers in women and men,” wrote the authors. “… our study provides robust evidence of an interaction between sex and beta-blocker therapy and suggests an increased risk of the composite endpoint of all-cause death, MI, or HF hospitalization, mainly in women with preserved LVEF receiving higher doses of beta-blockers.”¹

REFERENCES

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

2. Gerlach A. Closing the gap: Addressing underrepresentation of women in cardiovascular clinical trials. Pharmacy Times. May 24, 2024. Accessed September 3, 2025. https://www.pharmacytimes.com/view/closing-the-gap-addressing-underrepresentation-of-women-in-cardiovascular-clinical-trials

3. TREatment With beta-blockers After myOcardial Infarction withOut Reduced Ejection fraction. Updated June 6, 2025. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT03596385