Enrollment of women in cardiovascular clinical trials has traditionally been much lower than men. This limits the generalizability of the data creating a gap when it comes to making an impact in women’s cardiovascular health. Study design, inclusion criteria, and ability to recruit female participants have all be thought to play a role in the lack of equitable enrollment in many landmark cardiovascular trials.
Results from RCTs in heart failure between 1985-1999, include a mostly white, male population with only 21% of study participants being women even though women represent 50% of the general heart failure population. Furthermore, there is also a gap in age distribution in 60% of studies. The mean age of patients included in the study was 61. However, the mean age for heart failure is 75 [1]. Since the heart failure symptoms may present later in women, by limiting the age in clinical trials, we are not including a large proportion of the affected population. Similar trends can be seen in two studies that enrolled almost 20 years apart; the HPS and REVEAL trials. In both studies women were more likely to be excluded from the studies at various stages of trial screening. For instance, in the HPS trial, a trial that investigated the effect of Anacetrapib in patients with atherosclerotic disease, in the initial screening, 44% of the participants were women but only 18% of them entered the run-in. Ultimately, only 10% of women were randomized [2,3].
Despite the growing awareness of this recruitment gap and efforts to improve recruitment of women, there is much more improvement needed, as explained by the keynote speaker, Dr. Barbara Casadei, Foundation Professor of Cardiovascular Medicine at University of Oxford at the RISE 2023, Women as One conference.
In Dr. Casadei’s talk entitled, “Strategies to improve outcomes and care for women with heart disease: Research,” demonstrates the female under-representation in cardiovascular clinical trials and how to approach this discrepancy.
Dr. Casadei suggested that patient characteristics such as frailty, multimorbidity, and polypharmacy could be present in women more than men driving the differences in patient enrollment. Furthermore, she highlighted the lack of elderly and minorities. This makes the assessment of clinical trials difficult to generalize to the general population for therapy efficacy and adverse effects.
She also suggested several mitigating strategies to include more women as study participants such as avoiding the upper and lower age limits in inclusion of women and to increase efforts for the intentional recruitment for women. Additionally, she proposed using national dataset or registry data for long term pragmatic trials to increase representation of women in the studies. Dr. Casadei emphasized that using populations of trial subjects that do not represent inclusivity of women is not beneficial and can mislead the therapeutic plan.
Recognizing this important gap in clinical trial recruitment and implementing effective mitigating strategies will hopefully continue to move the needle towards equitable trial enrollment and improve diagnostic and therapeutic for all patients.
Dr. Maryam Barkhordarian is a Palisades Medical Center internal medicine resident and CardioNerds Intern and was CardioNerds Conference Scholar for the RISE 2023 conference hosted by Women as One.
References:
- Heiat A, Gross CP, Krumholz HM. Representation of the Elderly, Women, and Minorities in Heart Failure Clinical Trials. Arch Intern Med. 2002;162(15):No Pagination Specified. doi:10.1001/archinte.162.15.1682
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3. PMID: 12114036.
- HPS3/TIMI55–REVEAL Collaborative Group; Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, Wiviott SD, Cannon CP, Braunwald E, Sammons E, Landray MJ. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. 2017 Sep 28;377(13):1217-1227. doi: 10.1056/NEJMoa1706444. Epub 2017 Aug 28. PMID: 28847206.