Sex Differences in Statin Intolerance: Insights From the CLEAR Outcomes Trial

INTRODUCTION: The CLEAR Outcomes study showed that bempedoic acid reduced LDL cholesterol (LDL-C) and cardiovascular risk in patients with statin intolerance. CLEAR Outcomes included 48% female participants. OBJECTIVE: To describe the differences in baseline clinical characteristics and tolerability of bempedoic acid by sex. METHODS: Descriptive analysis of data from a double-blind, randomized, placebo-controlled cardiovascular outcome study in which 13 970 primary or secondary prevention patients at high cardiovascular risk with statin intolerance and baseline LDL-C ≥ 100 mg/dL were randomized to bempedoic acid 180 mg daily or placebo. RESULTS: At baseline, females (48%) were older, with less use of lipid lowering therapies, and more often without an ASCVD history. Females had more peripheral and cerebrovascular disease and less coronary artery disease. The incidence of myalgia was 5.4% versus 5.9% for females and 5.8% vs 7.6% for males treated with bempedoic acid versus placebo, respectively. Treatment discontinuation rates were lower with bempedoic acid than placebo in females (30.5% vs 33.4%) and males (27.9% vs 30.0%). Bempedoic acid discontinuation because of myalgia was comparable between females (1.8% vs. 1.6%) and males (1.7% vs 2.1%) versus placebo, respectively. CONCLUSIONS: This is the only cardiovascular outcomes trial to date that exclusively enrolled patients with statin intolerance, and the largest contemporary study of lipid lowering therapy in females, a group historically underrepresented in clinical trials. Bempedoic acid was equally tolerated by both sexes and represents a viable alternative to statins to reduce cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02993406.