Why We Support More Representative Trials in Cardiology

One such example are trials that study treatment options for heart failure. Researchers in Canada, the US, and UK recently looked at the MEDLINE, EMBASE, and CINAHL databases for randomized clinical trials that recruited adults with heart failure and a reduced ejection fraction. Researchers analyzed studies appearing in high-impact journals between January 2000 and May 2019 and found that women were under-enrolled in over 70 percent of heart failure trials, relative to how many women suffer from the condition. Furthermore, researchers found that these enrollment figures—averaging around 25 percent—did not change much over the 19-year window under review.  That led the researchers to conclude that trial design was likely a contributing factor, and that recruitment needed to address ways to get more representative data.

Some studies have already reported findings suggesting that women may even respond slightly better to CRT—but they draw from trials in which women were already underrepresented. De Waard et al used a post-hoc analysis of the RAFT trial to find that women had improved hospitalization and death rates using a CRT-D when compared with men. They were also less likely to suffer from ventricular arrhythmias. However, the authors themselves acknowledged that because fewer than 20 percent of the patients they analyzed were women, the data was still potentially underpowered. Dewidar et al put 97 studies together in a meta-analysis to find that women had a lower risk of all-cause mortality after CRT and experienced higher improvements in left ventricular ejection fraction. However, women made up only about 40 percent of the patients analyzed.

So how can we improve representation in trials to get better data? That’s what two BIOTRONIK-sponsored studies—BIOWOMEN and BIO-LIBRA—are working to answer. Although having experienced some delays in final enrolment due to COVID—19, BIOWOMEN has enrolled participants from 27 sites across seven European countries and Israel. It has enrolled 494 people—with as close to a 50-50 split between women and men as possible—who have a de novo indication for CRT implantation. Researchers will follow up after 12 months to see if there is a difference in CRT response between women and men.

Although BIO-LIBRA takes a slightly different approach, it too aims to improve the available data on whether gender influences responses to cardiac device therapy. Enrollment finished in October 2021, with 1,000 patients across 48 centers in the US. The study exceeded its goal of enrolling at least 40 percent women, who make up 47 percent of the participants! The trial investigates whether there is any difference between the sexes in how patients with non-ischemic cardiomyopathy respond to an ICD or CRT therapy.

Co-principal investigator Dr. Jeanne Poole says BIO-LIBRA will hopefully be able to help make future treatment guideline decisions that are well-informed with balanced data. “What is the response rate in women for defibrillator therapy—is it the same as men? We believe it should be. There’s no reason not to think that, but we simply don’t know from the randomized trials we’ve obtained to date,” she said in a previous interview. “We’ll be better able to identify compared to the prior data that we have, that women should or should not be receiving defibrillators in exactly the same way that men are.”

Dr. Valentina Kutyifa of the University of Rochester Medical Center pointed out in another interview with BIOTRONIK that BIO-LIBRA has so far been briefing trial recruiters to expect that women may take a little longer to make decisions about enrolling in a clinical trial than men might — something previous studies have confirmed. That may be because they consult more widely with family and friends before making decisions, but that doesn’t mean they’re any less interested in participating. Recruiters also use materials that are specifically targeted to women, rather than to an imagined general audience.

Finally, representation in cardiology itself plays a role. Only about 14 percent of American cardiologists, to use just one example, are women. Conversely, the Whitelaw et al review of 2000-2019 trials mentioned above found that heart failure trials where women were lead investigators tended to have higher proportions of women enrolled in their studies. Beyond supporting important trials like BIO-LIBRA and BIOWOMEN, in order to get more representative data, having better treatment for all potential cardiology patients involves making cardiology itself more representative. That’s why we proudly support all possible ways to get the best, most representative data possible.