Why Are We Still Seeing Gaps in Women’s Heart Care?

It is no secret that women have historically faced a number of disparities in heart disease research and, as a result, care.

For decades, women were systematically underrepresented in cardiovascular clinical trials, largely due to the misconception that heart disease was predominantly a male condition. This skewed focus on men’s health resulted in treatments and guidelines being developed without fully understanding how heart disease affects women differently. The issue was exacerbated in 1977 when the FDA issued guidelines that discouraged the participation of women of childbearing age in clinical trials due to concerns about potential harm to fetuses.¹ As a result, sex-specific differences in cardiovascular disease went largely unstudied.

It wasn’t until the 1990s that significant steps were taken to address this disparity. The National Institutes of Health (NIH) began requiring the inclusion of women in federally funded research, and more emphasis was placed on analyzing clinical trial data by sex. This policy was turned into federal law when Congress wrote it into a section of the NIH Revitalization Act of 1993.²

But, in the year 2024, why are women still being left out?

How Big Is the Gap in Clinical Trial Enrollment?

A review of 706 studies revealed significant underrepresentation of women in heart failure with reduced ejection fraction (HFrEF) trials.³ Only 26% of the participants across these studies were women, with no significant differences in their representation across various interventions, such as pharmacologic or device therapy.

Women have been underrepresented in heart disease clinical trials for decades | Image credit: Seventyfour – stock.adobe.com

Although female participation gradually increased toward the end of the decade, the median percentage of women in HFrEF trials remained under 50%. This under-enrollment challenges the generalizability of trial findings, given the known sex-based differences in heart failure characteristics and treatment responses. While efforts by government and industry stakeholders have led to some progress, further actions are necessary to identify and address barriers to female recruitment, ensuring trials are sufficiently powered to detect sex-specific interactions.

In a separate review of women’s participation across 740 cardiovascular trials between 2010 and 2017, researchers found that of more than 860,000 enrolled adults, 38.2% were women.⁴ Women were more represented in trials for hypertension and pulmonary hypertension, but less so in trials for arrhythmia, coronary heart disease, acute coronary syndrome, and heart failure.

Additionally, government-funded trials, studies with women aged 61 to 65 years, and procedural trials had much lower female representation than multi-sponsor–funded trials, studies with women aged 55 years and younger, and lifestyle intervention trials. While the review found notable increases in female participation in stroke and heart failure trials from 2013 to 2017, men still predominated in cardiovascular trials overall, highlighting the need for continued efforts to achieve gender equity in clinical research.

“The lower participation rate of women in cardiovascular clinical trials logically begs the question, ‘Why don’t women participate in trials at rates similar to men?’” the review authors said. “Hypothetically, multiple opportunities exist for a patient to fall out of the enrollment pathway, and several of these opportunities can likely be influenced by both patient-related and trial site–related factors.”

Why Are Women Still Being Left Out of Clinical Trials?

Women's underrepresentation in cardiovascular trials stems from various factors. As noted in the review from 2010 to 2017, awareness of trial opportunities is crucial, either through patient identification via consumer channels or through proactive engagement by study sites. Access to trial centers is another hurdle, requiring appropriate referrals and logistical support for transportation and childcare.

Kathryn Lindley, MD, FACC, associate professor of medicine and associate professor of obstetrics and gynecology at Vanderbilt University Medical Center, echoed this point during an exclusive interview with The American Journal of Managed Care^® (AJMC^®).⁵ She noted that women are often less likely to have health care insurance or access to transportation or childcare, as well as other barriers that may be less apparent.

“It's more difficult for women to participate in clinical trials because…you're busy working your job and taking care of your kids and taking care of your parents,” Lindley said. “It's physically more challenging to set aside time to participate in research studies, so a lot of our studies have really focused on men's health and not thought about the ways that it might be different for women.”

It’s also important for trial participants to not just understand but be comfortable with the clinical trial process and give informed consent.⁴ Additionally, cultural backgrounds, biases, communication approaches, and trial materials all influence women's comfort with enrollment. Studies have also indicated that women are generally less willing to participate in cardiovascular prevention trials compared with men, often due to perceptions of higher risk associated with trial participation.

“Women had also been shown to take fewer risks than men under stress, and large health-based decisions could certainly be a source of stress,” the review authors said. “Randomized clinical trials present an added element of risk and uncertainty, and women have been shown to be more reluctant than men to consider participation.”

The decision-making process can also differ between men and women, with women often requiring more time and external input, such as from friends, family, or health care providers. Women are also more likely to be influenced by altruistic or selfless motivations, such as participating for “the greater good” rather than for a financial incentive.⁶

To address these enrollment gaps, Lindley called for a multi-pronged, comprehensive approach that includes:

• Ensuring women have opportunities to participate in research
• Studying how sex and gender interact with cardiovascular health
• Educating clinicians on the differences in how heart disease affects women
• Empowering women to advocate for themselves and seek care when they sense something is wrong

“As clinicians, it's important that we're listening to our patients and are well educated on the ways that heart disease might affect women differently,” Lindley added.⁵ “Oftentimes women don't realize that they're at higher risk for certain heart conditions, so I think that's where it's really important that women just are able to access that knowledge and then advocate for themselves when they feel like something's not quite right.”

References

1. McCarthy CR. Historical background of clinical trials involving women and minorities. Acad Med. 1994;69(9):695-698. doi:10.1097/00001888-199409000-00002
2. NIH inclusion outreach toolkit: how to engage, recruit, and retain women in clinical research. NIH. Accessed October 14, 2024. https://orwh.od.nih.gov/toolkit/recruitment/history
3. Gulab A, Essa H, Lo KB, Sankaranarayanan R, Rangaswami J. Gender distribution in randomized controlled trials among patients with heart failure with reduced ejection fraction: a systematic review. Glob Heart. 2022;17(1):8. doi:10.5334/gh.1093
4. Jin X, Chandramouli C, Allocco B, Gong E, Lam CSP, Yan LL. Women's participation in cardiovascular clinical trials from 2010 to 2017. Circulation. 2020;141(7):540-548. doi:10.1161/CIRCULATIONAHA.119.043594
5. Klein HE. Dr Kathryn Lindley addresses barriers to women’s heart disease diagnosis. AJMC. June 15, 2024. Accessed October 14, 2024. https://www.ajmc.com/view/dr-kathryn-lindley-addresses-barriers-to-women-s-heart-disease-diagnosis
6. Lobato L, Bethony JM, Pereira FB, Grahek SL, Diemert D, Gazzinelli MF. Impact of gender on the decision to participate in a clinical trial: a cross-sectional study. BMC Public Health. 2014;14:1156. doi:10.1186/1471-2458-14-1156