Representation of Women and Older Patients in Trials of Lipid Lowering Therapy: A Systematic Review

Introduction: Lipid lowering therapies are the cornerstone of the management of atherosclerotic cardiovascular disease (ASCVD). We sought to assess the temporal trend of women and older patients participating in major clinical outcome trials of lipid lowering therapies.Hypothesis: Women and older patients might be underrepresented in clinical trials of lipid lowering therapies.Methods: A total of 60 clinical trials (490,142 patients; 32 trials of statin therapy, 12 of n-3 PUFA, 6 of PCSK9 inhibitors, 3 of ezetimibe, 5 of fibrates and 2 of niacin) with sample size of [greater than or equal]1000 patients and follow-up of [greater than or equal]1 yr were selected using PubMed and ClinicalTrials.gov (search years 1990-2018).Results: The median number of participants per trial was 5,407 (IQR, 1,062-26,502). Overall, the average representation of women was 31.5% (range, 0%-69%). There was a modest uptrend in women enrollment from 1999-2003 (26.3%) to 2015-2018 (33.6%) (P=0.01; Figure). The representation of women varied from 17% in niacin trials to 43% in trials of n-3 PUFA (P=0.06). Representation of women was highest in trials of hypercholesteremia (53%) followed by trials of primary prevention of ASCVD (41%, 42,712 of 103,155 patients) (P=0.10). Government funded trials had the higher proportion of women (48%) as compared to industry funded (31%) trials (P=0.05). Mean age (SD) of participants increased from trials in 1990-1994 (56.5 [2.12] yrs.) to 2007-2010 period (65.4 [3.67] yrs) (P=0.01). Mean age of participants was highest in trials of heart failure patients (69.3 [3.21] yrs) compared to trials that enrolled patients with stable coronary disease (61.8 [2.60] yrs), for primary ASCVD prevention (61.8 [4.82] yrs) and with chronic kidney disease (60.2 [6.94] yrs) (P=0.04).Conclusions: Enrollment of women and older patients has increased over time yet these groups have remained in the minority in contemporary trials of lipid lowering therapy.