Women Still Underrepresented in Key Cardiovascular Trials

Women continue to be underrepresented in many cardiovascular clinical trials, according to a new systematic review of 1079 trials registered from 2017 to 2023.1 In total, 1,396,104 participants were enrolled, of whom 571,641 (41%) were women. According to the study, women were especially left out of studies on arrhythmia, coronary heart disease (CHD), acute coronary syndrome (ACS), and heart failure.

The analysis, published in JAMA Network Open, evaluated trials by disease type, intervention, region, age distribution, sponsor, and study size, and contextualized enrollment using a participation:prevalence ratio (PPR), a metric that compares the share of women in a trial to the share of women with that condition in the underlying population. PPRs below 0.8 indicate underrepresentation; those above 1.2 suggest overrepresentation.

Where Gaps Are Largest

Women's trial participation went up during the COVID-19 pandemic. | Image credit: © Studio Romantic – stock.adobe.com

Across disease areas, the median female:male (F:M) ratio was lowest in trials focused on:

• Heart failure: 0.51
• Arrhythmias: 0.50
• CHD: 0.39
• ACS: 0.32

When benchmarked against population prevalence, median PPRs were low in trials on:

• ACS: 0.79
• Stroke: 0.74
• CHD: 0.66

On the other hand, trials in pulmonary hypertension (PH) and obesity enrolled proportionally more women, with median F:M ratios of 2.86 and 2.29, and PPRs around 1.3 and 1.44, respectively. According to researchers, these patterns likely mirror higher female prevalence and targeted outreach strategies in these domains.

Enrollment also varied by trial characteristics. Women were more likely to be included in studies led by research institutions (F:M, 0.97; PPR, 1.12) than in industry- or government-sponsored trials, which had ratios of 0.57 and 0.34, respectively. Lifestyle intervention trials showed higher female participation (F:M, 1.51) than drug or device studies, and US-based trials generally achieved higher PPRs than studies conducted in Europe or in multiregion global programs. Trials enrolling cohorts 55 years and younger enrolled higher proportions of women than trials with older median ages, reflecting disease states with younger onset among women.

“Drug trials for hypertension and dyslipidemia had comparatively higher enrollment of women, with hypertension drug trials showing a significant upward trend during the COVID-19 pandemic years,” researchers said. “Although device trials are often associated with lower female participation, the proportion of women did not differ significantly across intervention types (drug, device, or lifestyle).”

Using nonparametric trend testing, the investigators did not find a statistically significant overall change in women’s participation from 2017 to 2024 (z = 1.91; P = .06). Notably, however, there was a significant uptick in women’s participation between 2019 and 2022 (PPR, 0.98; z = 3.01; P = .003), driven largely by hypertension trials and coinciding with wider adoption of decentralized or hybrid trial designs utilizing telehealth and remote visits during the COVID-19 pandemic. Heart failure trials also showed a modest but significant increase in women’s participation across the study window (z = 1.99; P = .046).

“The COVID-19 pandemic tested the resilience of trial structures but also spurred innovation,” the authors said. “To our knowledge, this is the first study to document increased women’s participation in CV [cardiovascular] trials during the pandemic.”

Barriers and Levers for Change

According to the authors, these findings highlight both the progress and challenges in enrolling women in cardiovascular trials, as these gaps not only limit the generalizability of study findings but also perpetuate inequities in care.2

“This pattern underscores the need for prioritizing enrollment improvements not only based on PPR but also on disease burden,” they said.1 “Addressing these gaps requires both improved trial inclusion and broader strategies, such as sex- and gender-based education, clinician awareness, and tools like coronary artery calcium scoring for individualized risk.”

They also cataloged intersecting drivers of underrepresentation that span the trial lifecycle:

• Diagnostic and phenotype bias: traditional, male-centric diagnostic paradigms can miss female-predominant phenotypes such as ischemia with nonobstructive coronary arteries, limiting eligibility3,1
• Reproductive considerations: exclusion of pregnant and lactating individuals and stringent contraception requirements can depress enrollment among women of reproductive age, with industry-sponsored trials particularly constrained by liability concerns
• Age-related exclusions: upper age cutoffs and comorbidity restrictions disproportionately exclude older adults, despite later-life presentation of many cardiovascular conditions in women.
• Socioeconomic barriers: caregiving responsibilities, transportation, and rigid visit schedules may reduce participation; decentralized and hybrid models appeared to mitigate some of these barriers during the pandemic
• Reporting gaps and leadership: fewer than one-third of phase 3 cardiovascular trial publications report sex-stratified outcomes; trials led by female investigators tend to enroll more women, but women remain underrepresented in leadership roles

References

1. Rivera FB, Magalong JV, Bantayan NRB, et al. Participation of women in cardiovascular trials from 2017 to 2023: a systematic review. JAMA Netw Open. 2025;8(8):e2529104. doi:10.1001/jamanetworkopen.2025.29104
2. Bibbins-Domingo K, Helman A, Dzau VJ. The imperative for diversity and inclusion in clinical trials and health research participation. JAMA. 2022;327(23):2283-2284. doi:10.1001/jama.2022.9083
3. Klein HE. Empagliflozin shown to reduce endothelial dysfunction in women with INOCA. AJMC®. September 10, 2025. Accessed September 11, 2025. https://www.ajmc.com/view/empagliflozin-shown-to-reduce-endothelial-dysfunction-in-women-with-inoca