Abstract 12929: Heterogeneity in Primary and Secondary Prevention Studies of Statins and PCSK9 Inhibitors: Does One Size Fit All?

Abstract

Background: We aim to assess the heterogeneity of demographics, gender variability and outcomes reporting for subjects enrolled in RCTs studying the role of statins and PCSK9 inhibitors in primary and secondary prevention of CAD. Methods: RCTs and metanalyses were searched for the use of statins and PCSK9 inhibitors published in journals with impact factor > 4 between 1995 and 2020. RCT data was analyzed for gender, race and geographic location. Metanalyses were searched for the outcomes-level heterogeneity. Results: A total 31 statin-based RCTs for primary and secondary prevention of CAD were found, of which 29 were included with a total 172,871 patients (71.4% males vs. 28.6% females). In WOSCOPS trial, all 6595 subjects were males. Though most of these trials included global patient populations, 10% of the trials included exclusively North Americans. Fifteen of the RCTs (52%) did not have race data. Of the 14 RCTs which reported race: 67% White, 4% Black. The mean number of White and non-White patients were 3950 and 1768 respectively. For PCSK9 inhibitors with a total of 13 RCTs included in our study there were cumulative 85,806 patients with globally enrolled patient population and predominantly male 71% vs 29% females. Ten RCTs (77%) reported race: 82% White, 0.3% Black. The mean number of White and non-White patients were 4671 and 1058 respectively. The eleven statin metanalyses included 823,936 patients. Ten of the eleven metanalyses reported statistical heterogeneity via I 2 % (mean 53%) for different outcomes. Five of the eleven metanalyses included primary outcomes of all-cause mortality, and the rest included onset/progression of different types of cardiovascular disease. The seven PCSK9 inhibitor metanalyses pooled 376,885 patients. All 7 metanalyses reported heterogeneity via I 2 % (mean 48%) for different outcomes, of which 2 included primary outcomes of all-cause mortality. Conclusions: Significant gender and racial disparities exist in RCTs for primary and secondary prevention lipid lowering therapies. Enrollment in PCSK9 inhibitor trials was global and significant treatment effect heterogeneity existed in metanalyses. Inequalities in female and non-White participation may hamper generalizability of these crucial medications.