A major trial suggests women face worse outcomes than men when prescribed beta-blockers post-heart attack.
Beta-blockers may not be as helpful in women as men, with research showing that women who take the medication after a heart attack have worse outcomes.
Researchers found that women have a higher risk of dying, myocardial infarction or being hospitalised for heart failure within four years of a previous myocardial infarction if they were treated with beta blockers compared to men.
“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,” the researchers said in the European Heart Journal.
The analysis included 8438 myocardial infarction patients – including 1627 women – with left ventricular ejection fraction greater than 40%.
The Spanish and Italian researchers used data from the REBOOT trial – tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion – to conduct a sex-specific subgroup analysis.
The researchers assessed sex differences in the effect of beta-blocker therapy on all-cause death, myocardial infarction or hospitalisation due to heart failure over a median follow-up of 3.7 years.
“Women randomised to beta-blockers had a 45% higher relative risk (corresponding to an excess absolute risk of approximately 0.9% per year) of the primary composite outcome compared with those in the control group, mainly driven by increased all-cause mortality,” they wrote.
The researchers said trials assessing beta-blocker therapy after myocardial infarction were conducted decades ago and did not include enough women for robust analyses.
One meta-analysis of five randomised studies evaluating the effects of metoprolol on mortality included only 1121 women, they said.
“Although the analysis showed a similar reduction in cardiovascular death for both sexes, these findings – reported in 1992 – are unlikely to be generalisable to contemporary MI patients, who are managed with modern standards of care including early invasive strategies, complete revascularisation, troponin-based diagnostics, dual antiplatelet therapy (DAPT), and high-intensity statin treatment,” the authors wrote.
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The researchers said the two recent randomised clinical trials – REBOOT and REDUCE-AMI – evaluated the efficacy of beta-blockers in patients with myocardial infarction without reduced LVEF and showed no consistent clinical benefit in patients treated with the latest standards of care.
“These findings challenge the long-standing paradigm that advocated beta-blocker use in all post-MI patients regardless of LVEF,” they wrote.
“Whether this lack of benefit applies equally to women and men remains uncertain. However, there are plausible biological and clinical reasons to suspect that the treatment effect may differ by sex.”
The researchers said there was evidence showing differences in pharmacokinetics and pharmacodynamics of beta-blockers between women and men, and it was well established that women and men did not receive the same medical management after acute coronary syndromes (ACS).
“Although findings vary across studies, several reports suggest that women may experience worse long-term outcomes than men after ACS,” they wrote.
“These disparities have led some authors to propose the development of sex-specific cardiovascular guidelines.”
The researchers said the median dose of beta-blocker was the same for male and female participants, but they noted that the female participants were older – with a median age of 65 years compared to 60 years for men – and had more comorbidities such as hypertension, diabetes and dyslipidaemia.
“Women more frequently presented non-obstructive coronary arteries on index angiography (5.9% vs 1.7% in men) and less frequently underwent revascularisation,” they wrote.
“Compared with men, women were less frequently prescribed with DAPT, statins, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) and were less frequently referred to cardiac rehabilitation program.”
