For decades, beta-blockers have been a standard treatment for people recovering from heart attacks.
But new research suggests that this widely used drug may not always be safe for women, challenging long-standing medical practice and raising important questions about sex-specific care in cardiology.
The findings come from the REBOOT trial, the largest modern study of beta-blockers in heart attack patients who did not suffer severe loss of heart function.
The trial, coordinated by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and conducted in Spain and Italy, included more than 8,500 patients across 109 hospitals.
Results were presented at the European Society of Cardiology Congress in Madrid and published in the European Heart Journal.
Patients were randomly assigned either to receive beta-blockers in addition to standard post-heart attack care or to receive no beta-blockers.
They were then followed for nearly four years. When the data were analyzed, striking sex-specific differences emerged.
For men, beta-blockers showed no clear benefit or harm.
But for women, the picture was different: those prescribed beta-blockers had a significantly higher risk of dying, suffering another heart attack, or being hospitalized for heart failure compared with women who did not take the drug.
During the nearly four-year follow-up, women taking beta-blockers had a 2.7% higher risk of death than those not on the medication.
This increased risk was particularly evident in women whose heart function was completely normal after their heart attack, with a left ventricular ejection fraction of 50% or higher. Women with only mild impairment in heart function did not show this excess risk.
The study also found broader differences between male and female patients. Women presenting with a heart attack tended to be older, with more health problems such as high blood pressure, diabetes, and high cholesterol.
They were also more likely to experience heart attacks without blocked arteries. Despite these higher risks, women were less often prescribed other guideline-recommended treatments, such as statins, antiplatelet drugs, or cardiac rehabilitation.
Overall, women in the study had a worse prognosis than men, with mortality rates of 4.3% compared to 3.6% in men.
“These findings confirm what smaller studies have suggested: women not only have different heart attack profiles but may also respond differently to common treatments,” said Dr. Borja Ibáñez, the trial’s lead investigator. “Prescribing beta-blockers to women after an uncomplicated heart attack may, in some cases, do more harm than good.”
The researchers emphasize that a “one-size-fits-all” approach may not be appropriate. Instead, doctors should consider sex-specific responses when prescribing treatments after heart attacks. The REBOOT trial highlights the urgent need to rethink current guidelines and move toward more personalized therapies that take into account differences between men and women.
As Dr. Valentín Fuster, one of the study leaders, noted, “We have known for years that cardiovascular disease often looks different in women and men. Now we know that the treatments may need to be different too.”
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