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Am Heart J Plus
Am Heart J Plus
American Heart Journal Plus: Cardiology Research and Practice
2666-6022
Elsevier

S2666-6022(24)00070-3
10.1016/j.ahjo.2024.100427
100427
Editorial
Special issue: Women and cardiovascular trials
Volgman Annabelle Santos Annabelle_Volgman@rush.edu
⁎
Division of Cardiology, Rush University Medical Center, Chicago, IL United States of America
Rush Heart Center for Women, Chicago, IL United States of America
⁎ Corresponding author at: Division of Cardiology, Rush University Medical Center, Chicago, IL United States of America. Annabelle_Volgman@rush.edu
25 7 2024
9 2024
25 7 2024
45 100427© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
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pmcThe editors of this journal initiated a special issue focusing on the crucial topic and the progress of the inclusion of women in cardiovascular trials. It is widely acknowledged that women are often underrepresented in many cardiac trials, and this can lead to potential inappropriate management of cardiac disease in women. In this special issue of the American Heart Journal Plus, we present a collection of papers addressing various facets of this issue that seek to understand why more women are not participating in trials and suggest possible solutions to this problem.

Gianos et al. delve into the epidemiology of cardiovascular disease (CVD) in women [1]. They raised pertinent questions about the influence of hormones on CVD, with specific attention to the menstrual cycle, pregnancy, and menopause. In addition, what is the unique impact of psychological stress on women and differences in symptomatology?

Mattioli et al. summarize the reasons why “Teaching gender medicine can enhance the quality of healthcare.” [2].

Brown et al. critically assessed that despite the National Institutes of Health's (NIH) effort to increase women's participation in NIH-sponsored CVD trials, there would be no significant increase in enrollment if the single-sex-based trials, such as the Women's Health Study and the Women's Health Initiative, were excluded [3].

Carland et al. reviewed the pharmacologic basis for the need for sex-specific assessment of cardiovascular drug therapies [4]. They also reviewed the sex-specific reporting of landmark drug trials in hypertension, coronary artery disease (CAD), hyperlipidemia, and heart failure (HF). The good news is that several areas, including drug trials for cardiometabolic syndrome, hypertension, and newer anticoagulation trials, showed improvement in enrolling women. However, heart failure, acute coronary syndrome, device, or procedural trials have not improved in enrolling more women.

Han and Russo summarized the under-representation of women in implantable cardioverter defibrillator trials [5]. They stated that age and comorbidities may be partially responsible when excluded. Ciuffo and Redberg wrote an editorial about the paper by Han and Russo. They argued that until better data has been generated, it remains unclear if women have any benefit from ICD implantation for primary prevention, especially in the new area of therapy for heart failure [6].

Reza et al. summarize the medical literature regarding women's participation in heart failure clinical trials [7]. They also explain the evidence surrounding sex- and gender-specific barriers to enrollment in heart failure clinical trials and offer solutions to resolve this gender and sex disparity. Their chart on strategies to increase the enrollment of women in heart failure trials throughout the clinical trial lifespan is a great template for increasing women's participation in all trials to improve CVD outcomes. Some examples are educating women about clinical trials and providing resources to women from their caretaking duties to be able to participate in trials. They also suggest diversifying trial recruiters and investigators.

We included an example of a systematic meta-analysis by Rivera et al. that investigated sex differences in using sodium-glucose transporter 2 inhibitors (SGLT2is) in five randomized controlled trials of heart failure patients (36 % were females) [8]. My co-authors and I found that although SGLT-2is reduce the risk of primary composite outcomes in patients with heart failure in men and women, there were more adverse events in women than in men.

Filbey et al. also suggested many improvements in clinical trial design that can increase the enrollment of women [9]. These includediversifying research teams and recruiting and retaining women trialists, which is independently associated with increased enrollment of diverse women participants. It may help to modify the trial design by eliminating default sex-specific exclusion criteria, developing patient-centered consent and participation processes, incorporating pragmatic follow-up schemes, and incorporating sex/gender analysis into trial planning, which may also increase the enrollment of women participants. Another suggestion was for journals and funding bodies to require trials to report participants to prevalence ratios, sex-disaggregated trial flow, and sex-treatment interactions. Healthcare systems also have a role in helping create research-ready cultures that both enhance patient engagement in trials and expedite end-of-trial knowledge translation.

In the paper “Why is it important for male cardiologists to enroll more women in cardiovascular trials?” Mamas and Van Spall discussed the many reasons to enroll women in clinical trials and provided a great figure for this issue [10]. They highlight that enrolling more women in CVD trials will offer them the benefits of trial participation. It will close evidence gaps in treatment efficacy and safety in women, develop targeted strategies to improve care in women, and, lastly, achieve research and healthcare equity.

Finally, we included a paper showing the importance of the increasing need for cardiologists to understand how to treat transgender people. The study by Stamatiou and Kararigas showed that there is only a small number of CVD clinical trials that study or include transgender persons [11].

This special issue of the American Heart Journal Plus aims to catalyze action toward improving the representation of diverse populations in clinical CVD trials that better represent the population we treat. The proposed solutions offered by the various authors offer valuable insights that could address the under-enrollment of women and other marginalized groups, ultimately enhancing the quality and relevance of cardiovascular care.

Declaration of competing interest

Sanofi – consulting, Novartis and Janssen -clinical trials, Janssen – advisory board, Apple Inc – stock.
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References

1 Gianos E. Khaliq A. Pearte C. Epidemiology of cardiovascular disease in women - a long way from our “founding fathers” Am Heart J Plus 13 2022 100087
2 Mattioli A.V. Bucciarelli V. Gallina S. Teaching gender medicine can enhance the quality of healthcare American Heart Journal Plus: Cardiology Research and Practice 44 2024 100418
3 Brown R.M. Weinberg C. Ong C. Mieres J.H. Underrepresentation of women in cardiac imaging trials: a review Am Heart J Plus 13 2022 100102
4 Carland C. Hansra B. Parsons C. Lyubarova R. Khandelwal A. Adequate enrollment of women in cardiovascular drug trials and the need for sex-specific assessment and reporting Am Heart J Plus 17 2022 100155
5 Han J.K. Russo A.M. Underrepresentation of women in implantable cardioverter defibrillator trials Am Heart J Plus 14 2022 100120
6 Ciuffo L.A. Redberg R.F. Sex differences in ICDs for primary prevention: time to include women in ICD trials! Am Heart J Plus 16 2022 100141
7 Reza N. Gruen J. Bozkurt B. Representation of women in heart failure clinical trials: barriers to enrollment and strategies to close the gap Am Heart J Plus 2022 13
8 Rivera F.B. Tang V.A.S. De Luna D.V. Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: a systematic review and meta-analysis Am Heart J Plus 2023 26
9 Filbey L. Khan M.S. Van Spall H.G.C. Protection by inclusion: increasing enrollment of women in cardiovascular trials Am Heart J Plus 13 2022 100091
10 Mamas M.A. Van Spall H.G.C. Why is it important for male cardiologists to enroll more women in cardiovascular trials? Am Heart J Plus 13 2022 100090
11 Stamatiou R. Kararigas G. Participation of transgender and gender diverse persons in cardiovascular clinical trials American Heart Journal Plus: Cardiology Research and Practice 44 2024 100420
