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Optimal Doses of Heart Failure Medications in Men vs. Women
Study Questions:
Are there gender differences in the optimal dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers in patients with heart failure with reduced ejection fraction (HFrEF)?
Methods:
The study authors conducted a post hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with HF in whom initiation and up-titration of ACE inhibitors or ARBs and beta-blockers was encouraged by protocol. They included only patients with left ventricular ejection fraction (LVEF) <40%, and excluded those who died within the first 3 months. The primary outcome was a composite of time to all-cause mortality or hospitalization for HF. The median follow-up duration for the primary endpoint was 21 months (interquartile range, 15–27). They validated their findings in ASIAN-HF, an independent cohort of 3,539 men and 961 women with HFrEF. Because BIOSTAT-CHF and ASIAN-HF were not randomized controlled trials, the study authors adjusted for treatment indication bias.
Results:
Of 1,819 patients with LVEF <40% from the BIOSTAT-CHF study, 109 people died within the first 3 months (up-titration phase). A total of 1,710 patients were studied, of whom 402 (24%) were women. Among 1,308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs. 70 [12] years, p < 0.0001) and had lower bodyweights (72 [16] kg vs. 85 [18] kg, p < 0.0001) and heights (162 [7] cm vs. 174 [8] cm, p < 0.0001) than did men, although body mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs. 304 [23%], p = 0.61) and beta-blockers (57 [14%] vs. 168 [13%], p = 0.54). In men, the lowest hazards of death or hospitalization for HF occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These gender differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and beta-blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels.
Conclusions:
The authors of this study concluded that women with HFrEF might need lower doses of ACE inhibitors or ARBs and beta-blockers than men.
Perspective:
This is the first study to describe gender-specific outcome in relation to the prescribed dose levels of medications for HF. As we move towards personalized medicine, the important findings of this study suggest that the one-size-fits-all approach to management of HF is less than optimal. The findings of this post hoc study suggest that future HF clinical trials must have prespecified gender analysis to determine optimal doses for all genders.
Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Body Mass Index, Body Surface Area, Geriatrics, Heart Failure, Medication Therapy Management, Peptidyl-Dipeptidase A, Stroke Volume, Treatment Outcome, Women
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