Women are underrepresented in cardiac resynchronization therapy trials

Introduction: Current guidelines for cardiac resynchronization therapy (CRT) device implant are the same across both sexes however women have been traditionally underrepresented in randomized controlled trials (RCTs). We aimed to identify if the number of women included in CRT trials is representative of the real-world burden of heart failure (HF) in women.

Methods: RCTs evaluating the benefit of CRT in HF patients referenced in the 2012 EHRA/HRS expert consensus statement on CRT in HF were included. Studies were evaluated for gender representation, baseline variables, and gender-based analysis of outcomes.

Results: A total of 10 CRT trials including 8107 patients were studied. Of the total patient population in these RCTs, only 23% were women. Analysis of outcomes based on sex was reported only in 5 out of 10 trials. Of these five trials reporting sex-based outcomes, multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) and resynchronization-defibrillation for ambulatory heart failure trial (RAFT) showed a greater benefit in women compared to men. Both MADIT and RAFT trials had a lower ejection fraction (EF) cut-off in the inclusion criteria (EF ≤ 30%) compared to the studies that did not find gender-based differences in the outcome (inclusion criteria: EF ≤ 35% or 40%). Additionally, women had less ischemic cardiomyopathy and more left bundle branch block (LBBB) compared to men in these two trials.

Conclusion: Women are underrepresented in CRT trials; however, they have been shown to derive a greater benefit from CRT compared to men. Appropriate measures should be taken in future studies to enhance the participation of women in clinical trials for more generalizable evidence.