BACKGROUND AND PURPOSE:

• Medications for heart failure with reduced ejection fraction (HFrEF) include
  • Angiotensin-converting-enzyme (ACE) inhibitors | Angiotensin-receptor blockers (ARBs) | β blockers
  • Men and women are prescribed the same doses
• Santema et al. (Lancet, 2019) investigated whether there are sex differences in the optimal doses of these medications for HFrEF

METHODS:

• Post-hoc analysis of prospective BIOSTAT-CHF study (11 European countries)
  • Study to evaluate heart failure treatment with left ventricular ejection fraction less than 40%
  • Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF
• Primary outcome
  • A composite of time to all-cause mortality or hospitalization for heart failure

RESULTS:

• 1,308 men and 402 women
• Women were
  • Older (74 vs 70 years; p<0.0001)
  • Lower bodyweights (72 kg vs 85 kg; p<0.0001)
  • Heights (162 cm vs 174 cm; p<0.0001)
  • No difference in BMI
• A similar number of men and women reached guideline-recommended target doses
• Sex differences related to drug dosage and risk for death or hospitalizations for heart failure
  • Men: Lowest numbers of death or hospitalizations for heart failure occurred at 100% of the recommended medication dose
  • Women: 30% lower risk of death or hospitalizations at only 50% of the recommended doses and no further decrease in risk at higher dose levels
  • Adjusting for age and body surface area did not alter results
  • Findings were similar in the second ASIAN-HF study

CONCLUSION:

• Women may require half the dose of heart failure medications compared to men
• This finding is particularly important as literature demonstrates that women may have more adverse drug reactions and these reactions may be more severe than those seen in men
• This study highlights the pervasive bias towards male-based medical guidelines in research and in addition the authors state

This study also underlines the importance of performing prespecified sex-specific analyses in all drug trials

Learn More – Primary Sources:

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

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