Review: Heart failure trials lack women, older patients
Although heart failure researchers have made strides in enrolling more racial and ethnic minorities in clinical trials, women and older patients remain underrepresented, according to a systematic review published in JAMA Cardiology.
Those subgroups are disproportionately affected by heart failure, wrote researchers led by Ayman Samman Tahhan, MD, with Emory University School of Medicine in Atlanta. And the continued underrepresentation of these patients in clinical trials could limit the studies’ generalizability to real-world settings.
“Given important biological differences by age, sex, and race/ethnicity, the risks and benefits of tested therapies may be anticipated to differ based on differing demographic profiles,” Tahhan et al. wrote. “Furthermore, ensuring adequate representation of key demographic subsets concordant with the U.S. HF population may also affect regulatory decision making for drug/device approval.”
The authors analyzed 118 trials published from 2001 through 2016 which encompassed more than 215,000 patients. They found:
- The mean age of participants in heart failure with reduced ejection fraction (HFrEF) trials was 65, while the mean age of those in HF with preserved ejection fraction (HFpEF) trials was 71. Those averages are four and two years younger, respectively, than the typical patient with those conditions based on U.S. epidemiological studies.
- 56 percent of HFpEF trial participants were women, compared to 24 percent of HFrEF trial enrollees. Women are estimated to comprise 62 and 29 percent of HFpEF and HFrEF patients, respectively, in the U.S.
- The proportion of nonwhite participants increased from 13 percent for studies published in 2001 to 2004 to 30 percent for those published in 2013 to 2016.
“Differences in traditionally underrepresented patient groups between trials and epidemiologic studies persist but are less than previously reported,” Tahhan and colleagues concluded. “Enrollment of racial and ethnic minorities has improved over time but may be subject to reporting bias.”
That potential bias results from less than half of studies reporting any race/ethnicity data for their enrollees, as well as incomplete data in other cases.
The authors advocated for complete reporting of race/ethnicity data in future trials. Even if those studies are underpowered to draw race-specific conclusions about outcomes, subgroup analyses may help guide hypotheses for future studies, they said.
Tahhan et al. also noted the increase in nonwhite participants over time was driven primarily by Asian patients, who represented just 1 percent of study patients in the early years of the analysis but 20 percent during the final years. Participation among blacks actually dropped over time, from 8 percent to 5 percent.
“The inclusion of industry-sponsored trials with increasing global sites (many of which are located in Asia) may explain the relative increase in Asian enrollment over time while representation of black individuals remains poor,” the authors wrote.
As for the lack of older patients, Tahhan and colleagues acknowledged it is often difficult to enroll them in trials based on strict exclusion/inclusion criteria, the intensity and duration of follow-up and testing and a lack of financial and social support.
“Characterizing and addressing limitations to enrollment are vital to strategically improving the design and representation of all age groups in HF clinical trials,” the researchers noted. “Continued efforts to improve reporting of age, sex, and race/ethnicity data within HF clinical trials and enhance the representativeness of trial populations are needed.”
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.