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