Heart failure: women may benefit from lower medication doses

  • Lancet

  • International Clinical Digest
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Takeaway

  • Women with heart failure with reduced ejection fraction (HFrEF) might benefit from lower doses of common therapies, even though guidelines recommend up-titration to maximal doses.
  • This observational study found sex differences in optimal doses of angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARB), and beta-blockers.

Why this matters

  • Editorial: this “thoughtful and thorough” study fills a gap and suggests that up-titration in women offers no additional benefit.

Key results

  • Numbers reaching the target doses for all 3 drug classes were similar between sexes, but outcomes at percentage of target dose were not.
  • Women showed a U- or J-shaped dose response for all drugs with titration from 1% to 100% of target dose.
  • Benefit for women peaked at about 60% of target dose for beta-blockers and at about 40% of ARB/ACEi target doses before fading out with increasing doses.
  • Men, on the other hand, showed a steady decline or plateau as doses approached 100% of target.
  • Validation using separate registry data showed a similar pattern.

Study design

  • Post hoc analysis of prospective, multinational BIOSTAT-CHF10 study (n=1710; 24% women).
  • Results validated using ASIAN-HF data (n=4500).
  • HFrEF: left ventricular ejection fraction
  • Outcome: composite of all-cause mortality/HF hospitalization.
  • Funding: European Commission.

Limitations

  • Post hoc; no assessment of side-effects, serum drug concentrations; disproportionately male.