Women Remain Underrepresented in Cardiovascular Trials, Perpetuating Healthcare Inequities
new research reveals persistent underrepresentation of women in cardiovascular clinical trials, hindering the generalizability of findings and exacerbating existing disparities in care. A systematic review published in JAMA Network open in 2025, analyzing trials from 2017 to 2023, highlights ongoing challenges in achieving equitable enrollment.
The study underscores that prioritizing enrollment improvements based on population proportion representation (PPR) alone is insufficient, and must be coupled with consideration of disease burden. Researchers advocate for sex- and gender-based education for clinicians, increased awareness, and individualized risk assessment tools like coronary artery calcium scoring.
Several intersecting factors contribute to this underrepresentation throughout the trial lifecycle. Diagnostic and phenotype bias, stemming from traditionally male-centric diagnostic criteria, can lead to missed diagnoses of female-predominant conditions like ischemia with nonobstructive coronary arteries. Strict exclusion criteria related to reproductive health – including the exclusion of pregnant and lactating individuals and stringent contraception requirements – also significantly limit enrollment among women of reproductive age, particularly in industry-sponsored trials due to liability concerns.
Age-related exclusions, such as upper age cutoffs and comorbidity restrictions, disproportionately impact older women, despite the fact that many cardiovascular conditions manifest later in life in this population. Socioeconomic barriers,including caregiving responsibilities,transportation issues,and inflexible visit schedules,further impede participation,though decentralized and hybrid trial models showed some promise in mitigating these challenges during the pandemic.
The review also points to systemic issues within trial reporting and leadership. Fewer than one-third of phase 3 cardiovascular trial publications report sex-stratified outcomes. Trials with female investigators tend to enroll a higher proportion of women, yet women remain significantly underrepresented in leadership roles.
“Addressing these gaps requires both improved trial inclusion and broader strategies,” the researchers stated.
The study’s findings build upon previous calls for diversity and inclusion in clinical research, as emphasized by Bibbins-Domingo, Helman, and Dzau in a 2022 JAMA article highlighting the imperative for equitable participation.
References:
- 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
- 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
- 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
