Pharmacological treatments for heart failure showed no significant sex differences in efficacy, with pooled difference in log(REM) between women and men of 0.01 (p=0.76).
Do pharmacological treatments for heart failure have different efficacy in women compared to men?
Pharmacological treatments for heart failure demonstrate similar relative efficacy in women and men across randomized controlled trials, suggesting that the historical underrepresentation of women has not obscured meaningful sex-specific differences in therapeutic efficacy.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Women have historically been underrepresented in heart failure (HF) trials, which raises concerns about potential undetected sex-related differences in treatment efficacy. Limited enrollment of women in randomized controlled trials (RCTs) may obscure potential variations in drug response between women and men. It remains unclear whether increasing female representation in RCTs would reveal meaningful sex-specific differences in therapeutic outcomes. Purpose This study aims to assess sex differences in HF treatment efficacy and explore whether these differences are influenced by the proportion of women included in trials. Methods A systematic search of Embase, Medline Ovid, and Cochrane Central was conducted up until May 7, 2024. RCTs comparing any pharmacological treatments for HF against placebo or usual care and assessing clinical events as the primary outcome were included. A meta-analysis using a random-effects model was conducted to evaluate sex differences in the relative effect measure (REM) of the primary efficacy endpoint and to obtain a pooled estimate of this difference. Additionally, a meta-regression was performed to examine the relationship between the proportion of women in the trial and both the sex differences in REM and the point estimate of the REM. Results Of 5,297 publications screened, 133 RCTs met inclusion criteria. These RCTs investigated various types of pharmacotherapies, ranging from beta-blockers to SGLT2-inhibitors, with a range of endpoints, including all-cause mortality and hospitalization for HF. The inclusion rate of women ranged from 1% to 60% of the total trial population. Based on 70 RCTs that provided sex-stratified information on the REM, we found no sex-differences in primary efficacy outcome: the pooled difference in log(REM) between women and men was 0.01 (95% confidence interval –0.03, 0.04; p-value 0.76; heterogeneity I2: 0.0%), see Figure 1 (meta-analysis). Meta-regression neither showed a significant association between the proportion of women in the trial and sex differences in efficacy (70 RCTs, p-value 0.25), nor with the magnitude of the point estimate of the primary endpoint (133 RCTs, p-value 0.35); see Figure 1 (meta-regression A and B). Conclusions This meta-analysis demonstrated similar relative efficacy of treatments for HF in women and men across all RCTs evaluated. Specifically, the pooled results of over 100 RCTs suggest that potential differences in drug efficacy between sexes are unlikely to have been missed. A key objective of RCTs is to assess efficacy. Hence, these findings provide reassurance in the context of ongoing discussions about the underrepresentation of women in clinical (HF) trials. However, although beyond the scope of this research, safety and adverse effects also play a role in clinical practice. Therefore, systematic analyses of sex differences in this regard are warranted in future research.Figure 1:graphical abstract
Bijl et al. (Sat,) reported a other. Pharmacological treatments for heart failure showed no significant sex differences in efficacy, with pooled difference in log(REM) between women and men of 0.01 (p=0.76).