Including more females in cardiac device trials can benefit all patients

A cardiac device trial published in eClinicalMedicine shows that improving enrollment of females in such trials can better guide care for all patients.

The BIO-LIBRA study investigated how well implantable cardiac defibrillators work for patients with non-ischemic cardiomyopathy, a weakening of heart muscle that is more common in females. Because nearly 48% of study participants were assigned female at birth—a number that is unheard-of in cardiac device trials—the one-year interim study results revealed that participants assigned male at birth were twice as likely to die or experience life-threatening heart rhythm abnormalities.

“This is the first study that had a large enough number of females enrolled to show this difference,” said Valentina Kutyifa, MD, Ph.D., professor of Medicine, Cardiology Heart Research at the University of Rochester Medical Center and co-lead of BIO-LIBRA.

“We learned that patients with non-ischemic cardiomyopathy do well with these devices, but they still have a residual risk of developing life-threatening ventricular arrhythmias or dying, and this risk is lower in females. Our data will help clinicians identify patients at higher risk and potentially intensify their treatment.”

The study enrolled 1,000 patients with non-ischemic cardiomyopathy and investigated how well they did with devices commonly used to treat the disease. Patients received either an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRT-D) to monitor heart rhythm and deliver impulses to correct irregular beats and/or coordinate heart contraction.

One year after device implantation, 13% of males in the study had experienced a life-threatening heart rhythm abnormality or died, compared to just 6% of females. While the rate of arrhythmias or death among female participants is clinically meaningful, it amounts to a 52% lower risk.

The trial will continue to monitor patients to evaluate the differences in rates of arrhythmias and death between male and female patients at three years after device implantation.

Representation matters

Despite making up roughly half of the global population, females have historically been underrepresented in research generally, and particularly in medical device trials. The original trials testing ICDs and CRT-Ds led by URMC researchers decades ago focused on ischemic cardiomyopathy, which is more common in males, and only enrolled 15–29% females.

This gap in the data may have contributed to the fact that females are less likely to be treated with ICDs or CRT-Ds.

When Kutyifa and Jeanne Poole, MD, professor of Medicine at UW Medicine, designed the BIO-LIBRA study, they set out to fill this data gap. To enroll more females and better reflect the demographics of patients impacted by non-ischemic cardiomyopathy, they had to address multiple barriers that prevent females from enrolling in studies.

“Clinical trials might be too much of a time demand, too much to juggle with family, because females are still more likely to be caregivers,” said Kutyifa. “Females may not know about studies, and doctors and study staff may assume females are at low risk or ineligible for a study.”

To address those barriers, Kutyifa and Poole designed the study visits to coincide with regular care appointments and used remote monitoring to reduce the study time demands. Unlike previous studies, they did not exclude patients based on age or comorbidities, which can inadvertently disproportionately exclude females. They educated study teams about the importance of increasing female participation in clinical trials and provided practical guidance to help teams enroll more females.

That extra effort was well worth it. Not only did Kutyifa and Poole blow past their goal of enrolling 40% females, but they also enrolled greater proportions of several other groups that are typically underenrolled.

“As we’ve shown in this study, enrolling participants that better reflect the actual patient population benefits everyone, not just those who have been left out in the past,” Kutyifa said.