A study published in February 2020 in the journal Circulation found that, in a decade worth of cardiovascular studies, women constituted 38.2 percent of research participants, much lower than previous reports indicated. And that’s a problem, the researchers say, because the female heart is different from the male heart. “Many women — even many healthcare providers — do not recognize that heart disease is the No. 1 killer of women around the world,” says Joseph A. Hill, MD, PhD, chief of cardiology at the University of Texas Southwestern Medical Center in Dallas and the editor in chief of Circulation. “It is vitally important that we study females with or at risk for heart disease,” he says. According to Dr. Hill, the female heart is typically a bit smaller than a male’s, which means the arteries are smaller, too, so different treatments or devices, such as smaller stents, might be necessary. “The effects of sex hormones, both estrogen and androgens, are different and the genetic blueprint of the female heart is different from the male heart. To some extent, heart disease in women can manifest differently than in men,” says Hill. RELATED: Heart Attacks Are Becoming More Common in Younger Women
Analysis a ‘Loud and Necessary Reminder’ to Be Mindful of Sex Differences
To determine the difference in clinical trial representation according to gender, investigators performed a comprehensive analysis of 740 cardiovascular trials reported between January 1, 2010, and December 31, 2017, on ClinicalTrials.gov. There were a total of 862,652 adults in the studies, and the average age for both men and women was 60.8, with the age range between 25 and 89 years old. The following trends were reported:
Only 26 percent of women between the ages of 61 and 65 were enrolled in trials despite having the largest number of trials registered for this age group.Participation of women versus men in clinical trials was comparable for stroke, pulmonary hypertension, and hypertension trials, but low in coronary heart disease and acute coronary syndrome and lowest in heart failure trials, relative to their respective real-world disease prevalence.The lowest proportions of women were in government-sponsored trials (excluding National Institutes of Health trials). The authors suggested this is because many trials are sponsored by the Veterans Affairs Office of Research and Development, and over 90 percent of veterans are male, according to the National Conference of State Legislators, making it difficult to have adequate female representation when recruiting from this group.
On a hopeful note, there have been significant increases in recruitment of women into stroke and heart failure trials in the last few years, a commendable effort to push things in the right direction, says Chanchal Chandramouli, PhD, coauthor and clinical research fellow at National Heart Centre Singapore. Although participation in heart failure trials significantly improved in 2016–2017, heart failure still remains near the bottom for participation among women. “Our study serves as a loud and necessary reminder for physicians to be mindful of sex differences in disease diagnosis, manifestation, treatment, and prognosis,” says Dr. Chandramouli.
Why Is It Important for Women to Participate in Cardiovascular Trials?
Although cardiovascular disease is the No. 1 cause of death in men and women, there have been several important studies that have highlighted sex differences in pathophysiology, clinical presentation, and outcomes, according to Chandramouli. “A classic example is the recent PARAGON-HF trial [published in October 2019 in The New England Journal of Medicine], which recruited more women than most prior heart failure trials,” she says. The study identified a greater treatment benefit in women than men with heart failure and preserved ejection fraction, a measurement of the amount of blood that leaves the heart each time it contracts, when given a combination of sacubitril-valsartan compared with valsartan, according to Chandramouli. “This finding would have never been possible without sufficient numbers for sex-stratified analyses,” she adds. Including both men and women in clinical trials, as well as people from different ethnic groups, is necessary to ensure that each person is getting the treatment that is best for them, according to Pamela Ouyang, MBBS, director of the Johns Hopkins Women’s Cardiovascular Health Center in Baltimore. “These therapies or interventions coming out of trials are going to be used to treat everyone; the more representation of every kind of person that’s going to be receiving that therapy, the better. The more data that is collected can help ensure that there’s no differential in efficacy, side effects, or adverse events,” says Dr. Ouyang.
A History of Excluding Women in Many U.S. Clinical Trials
In 1977, the U.S. Food and Drug Administration issued a policy that actually recommended excluding women who were able to have children from Phase 1 and early Phase 2 drug trials, even if they used contraception, were single, or their husbands had had a vasectomy, according to the National Institutes of Health (NIH). This policy was mostly due to a few drug-related incidents that resulted in great harm for some people, particularly with women who took the drug thalidomide. The drug, developed in the 1950s, was marketed as a mild sleeping pill even for pregnant women. But it caused thousands of babies to be born with malformed limbs. Because this policy resulted in a shortage of data on how drugs impacted women, there was pushback from many who advocated for women to be able to choose themselves whether to take on the potential risk of participating in a clinical trial. In 1987, the NIH published a new policy that encouraged researchers to include women in studies, and it became a Federal law in 1993, called the Women and Minorities as Subjects in Clinical Research. According to the law, trials should be designed and executed to examine how different variables may affect women and minorities differently, and cost is not an acceptable reason for excluding minorities and women. And yet, participation of women in clinical trials is still lacking. Chandramouli believes that the institutions and companies could do a better job of informing women of the opportunity to participate in trials through effective consumer channels or study investigators. “Sex-specific trial education materials and recruitment strategies could also potentially help,” she says.
How Can I Get Involved in a Clinical Trial?
The National Institutes of Health (NIH) Clinical Trial Registry lists more than 200,000 trials in over 190 countries. You can search for a trial according to the disease or condition, medication or therapy used, or site country. Tips for how to find a clinical trial for a specific condition can be found at the NIH website. If you don’t have a specific disease but you’re interested in participating in and even driving the direction of research, the American Heart Association has something called Project Baseline, according to Ouyang. This project is a way for individuals to participate in clinical research, surveys, and focus groups. “It’s a way for people to share what health issues people think are important and where they would like to see more medical research,” says Ouyang. Research Goes Red is part of Project Baseline, with the stated goal of trying to empower women to contribute to health research and find new ways to treat, beat, and prevent heart disease in women. By joining the project (which costs nothing) you can sign up to be alerted when a study that matches your medical condition or interests becomes available. The bottom line: Research has made it clear that the hearts of men and women are wired differently, says Chandramouli. “Instead of dismissing these differences, let’s embrace them. The only way to do so is to have adequate representation of women in cardiovascular trials, comparable with their real-life disease prevalence figures,” she says. “This will enable the medical community to tailor sex-specific therapeutic options based on differing drug efficacies and responses,” she adds.
