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Trial characteristics associated with under‐enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review
Author(s) -
Whitelaw Sera,
Sullivan Kristen,
Eliya Yousif,
Alruwayeh Mohammad,
Thabane Lehana,
Yancy Clyde W.,
Mehran Roxana,
Mamas Mamas A.,
Van Spall Harriette G.C.
Publication year - 2021
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.2034
Subject(s) - medicine , ejection fraction , confidence interval , randomized controlled trial , heart failure , odds ratio , ambulatory , logistic regression
Aims To evaluate temporal trends in the enrolment of females in randomized controlled trials (RCTs) of heart failure with reduced ejection fraction (HFrEF) published in high‐impact journals, and assess RCT characteristics associated with under‐enrolment. Methods and results We searched MEDLINE, EMBASE and CINAHL for studies published from January 2000 to May 2019 in journals with impact factor ≥10. We included RCTs that recruited adults with HFrEF. We used a 20% threshold below the sex distribution of HFrEF to define under‐enrolment. We used multivariable logistic regression to assess trial characteristics independently associated with under‐enrolment. We included 317 RCTs. Among the 183 097 participants, mean (standard deviation) age was 63.0 (7.0) years and 25.5% were female. Females were under‐enrolled in 71.6% [95% confidence interval (CI) 66.6–76.6%] of the RCTs; enrolment did not increase significantly between 2000–2019. Sex‐related eligibility criteria [odds ratio (OR) 2.05, 95% CI 1.01–4.16; P = 0.046]; recruitment in ambulatory settings (OR 2.56, 95% CI 1.37–4.81; P = 0.003); trial coordination in North America (OR 4.44, 95% CI 1.09–18.07; P = 0.037), Europe (OR 6.79, 95% CI 1.63–27.39; P = 0.018) and Asia (OR 9.33, 95% CI 1.40–12.40; P = 0.033); drug (OR 1.76, 95% CI 1.96–7.36; P < 0.001) and device/surgical interventions (OR 1.69, 95% CI 1.16–9.43; P = 0.002); and men in first and last authorship position (OR 1.32, 95% CI 1.12–3.54; P = 0.047) were associated with under‐enrolment of females. Conclusions Females were under‐enrolled relative to disease distribution in a majority of high‐impact HFrEF RCTs, with no change in temporal trends between 2000 and 2019. Trial characteristics and gender of trial leaders were associated with under‐enrolment.