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.

Introduction: Ivabradine has been shown to be associated with atrial fibrillation (AF) in a metanalysis of 11 studies, however, AF has not been routinely reported as an adverse event of ivabradine in clinical trials. The FDA Adverse Event Reporting System (FAERS) is a publicly available database of adverse events (AE) of various drugs. We analyzed the database for real-world AF reporting with Ivabradine. Methods: FAERS was searched for the adverse events reported for ivabradine. All AF cases were individually analyzed. Results: A total of 3550 AE reports of Ivabradine were reported to FAERS from April 2011 to August 2021 out of which 1117 were cardiac adverse events. A total of 78 cases of AF were reported, accounting for 2.1% of the total AE reports and 31% of cardiac AE reports. Sex was reported in 83% of total AF cases, of which 50% were male, and the other 50% were female. 79% of the AF cases were reported by health care professionals, and 21% by consumers. 51% of cases were reported from the United States, 10% from France, and 9% from Germany. In 51% of the cases, no concomitant drug was given with ivabradine, and in 49% a concomitant drug was given; 10% of those was Digoxin/Digitalis that has been associated with AF. When searched using OpenVigilFDA (a web-based user interface to the FAERS for extraction and analysis of adverse events reports), the reporting odds ratio (ROR) of Ivabradine for AF was 3.18 (95% CI: 2.46 - 4.10) and the proportional reporting ratio was 3.15. The comparison of RORs of ivabradine with the drugs traditionally known to cause AF is shown in the figure. Conclusions: Disproportionate reporting of AF with ivabradine indicates that AF is associated with Ivabradine use. Further studies are required to confirm this association