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

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• The CLEAR Outcomes study demonstrated bempedoic acid's efficacy in reducing LDL cholesterol and cardiovascular risk among patients intolerant to statins.
• This trial included a significant proportion of female participants (48%).

Purpose of the Study:

• To investigate and delineate the differences in baseline clinical characteristics between sexes.
• To assess and compare the tolerability of bempedoic acid in female and male participants.

Main Methods:

• A descriptive analysis was conducted on data from a large, double-blind, randomized, placebo-controlled cardiovascular outcome study.
• 13,970 high-risk patients with statin intolerance and elevated LDL-C (≥100 mg/dL) were randomized to receive either bempedoic acid (180 mg daily) or a placebo.

Main Results:

• At baseline, female participants were older, used lipid-lowering therapies less frequently, and were more likely to lack a history of atherosclerotic cardiovascular disease (ASCVD).
• Females exhibited higher rates of peripheral and cerebrovascular disease but lower rates of coronary artery disease compared to males.
• The incidence of myalgia and treatment discontinuation rates due to myalgia were comparable between sexes for both bempedoic acid and placebo groups.

Conclusions:

• This trial is unique as the only cardiovascular outcomes trial exclusively enrolling patients with statin intolerance.
• It represents the largest contemporary study of lipid-lowering therapy in females, addressing historical underrepresentation in clinical trials.
• Bempedoic acid demonstrated equal tolerability in both sexes and is a promising alternative to statins for reducing cardiovascular risk.