Sex Diversity in Heart Failure Clinical Trials

Corresponding Author

D espite substantial advancements in guideline-based medical therapies, heart failure (HF) persists as a major global health challenge, impacting millions worldwide including a high prevalence of women. 1 Despite women being affected by HF more commonly than men across certain age groups and growing knowledge suggesting marked sex differences in presentation, clinical trajectory, response to therapy and outcomes, women patients remain underrepresented in clinical trials, and sex-specific data are lacking. 2,3Of note, throughout this editorial, we use the term sex to refer to the biological variable that is genetically determined (female/male), as opposed to gender, which is a multidimensional social construct (women/ men).Since the vast magnitude of clinical studies rely on self-identified gender, we opted to use the terms women/men as a proxy for biological sex, while acknowledging that this has complex limitations.
In this issue of JACC: Advances, Ekpo et al 4  The authors should be commended for their study, which once again highlights the well-documented lack of enrollment of women across HF clinical trials.The present study reiterates this disparity but, more importantly, should serve as a catalyst for change.Diversity is known to be a driver of innovation and excellence in medical research.However, the field of cardiology has yet to fully harness this potential, primarily due to the persistent underrepresentation of women. 6This gap not only hinders the development of more inclusive and effective HF care but also represents a missed opportunity for leveraging diverse perspectives that can lead to groundbreaking advancements in the field.Including women in HF trials is vital for several reasons.unveiling novel therapeutic targets.Ultimately, embracing sex diversity in HF research not only enhances the scientific rigor and relevance of the studies but also leads to more equitable health care outcomes, ensuring that both men and women benefit equally from the advancements in HF treatment and management.
The underrepresentation of women in HF clinical trials is a known and persistent problem. 2,6At this point, this matter demands more than acknowledgment; moving beyond mere words, it's time for immediate, deliberate, and action-oriented solutions.
Effectively addressing these disparities requires a multifaceted approach, including the commitment from researchers, regulators, and industry to ensuring that women are adequately represented in all aspects of clinical research, from trial design to execution and analysis (Figure 1).Among possible solutions, it has been shown that enrollment of women in clinical trials is more likely to occur when female investigators are part of the trial leadership; as such, increasing the representation of female researchers is critical.doubling the typical proportions seen in similar studies. 7Importantly, the Food and Drug Administration had a recent policy change that underscores this commitment to diversity, whereby it requires sponsors to submit comprehensive plans for enrolling diverse patient groups, providing clear targets and strategies for achieving these goals. 8Similarly, In conclusion, the study by Ekpo et al 4 present a thought-provoking study that adds to the growing body of evidence indicating that women are underrepresented in HF clinical trials.In their analysis, they specifically included HF clinical trials that observed mortality or hospitalization for HF, and they mirrored the timeline used by the 2022 American Heart Association/American College of Cardiology/ Heart Failure Society of America Guidelines for the Management of Heart Failure, 5 which included studies that were published through September 2021.Their final analysis comprised 33 randomized controlled trials with 104,972 trial participants; among these, only 23.2% were women (n ¼ 24,366), with an overall participation prevalence ratio of 0.58 indicating significant underrepresentation.There was no change in representation over time, and underrepresentation was observed across all geographic regions of enrollment and trial funding type, though government-funded trials were significantly less representative than industry-funded trials.
Diverse participant pools lead to more comprehensive data, ensuring that findings are applicable to a broader section of the population.This inclusivity also aids in identifying unique drug responses and potential side effects across different groups, thereby enhancing the safety and efficacy of medical therapies.Furthermore, the inclusion of women in HF trials can reveal valuable insights into sex-specific disease mechanisms and progression, potentially ISSN 2772-963X https://doi.org/10.1016/j.jacadv.2023.100786*Editorials published in JACC: Advances reflect the views of the authors and do not necessarily represent the views of JACC: Advances or the American College of Cardiology.From the a Inova Schar Heart and Vascular, Falls Church, Virginia, USA; b Abiomed, J&J MedTech, Danvers, Massachusetts, USA; and the c Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate.For more information, visit the Author Center.

FIGURE 1 4 Sex
FIGURE 1 Increasing Representation of Women in HF Clinical Trials As we move forward, it is crucial to translate our understanding of this issue into action, ensuring that clinical research in HF and beyond truly reflects and serves the diverse population it aims to heal.The future of equitable and effective medical therapy depends on our ability to embrace and implement these changes.FUNDING SUPPORT AND AUTHOR DISCLOSURESDr Bogaev serves as vice president for heart failure at Abiomed, Inc.All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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