Bempedoic Acid and Venous Thromboembolism Risk Among Statin-Intolerant Patients

Importance: Venous thromboembolism (VTE), which encompasses deep vein thrombosis and pulmonary embolism, is a frequent condition that can lead to significant morbidity and mortality; statins, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and their combination are associated with a reduced risk of VTE. The effect of bempedoic acid on VTE risk is unknown. Objective: To determine whether bempedoic acid is associated with a reduced risk of VTE. Design, Setting, and Participants: CLEAR Outcomes was a randomized, double-blind, placebo-controlled, cardiovascular outcomes clinical trial. Statin-intolerant individuals at high risk for or with established atherosclerotic cardiovascular disease who were aged 18 to 85 years were enrolled between December 22, 2016, and August 14, 2019, in 1250 centers across 32 countries. The statistical analysis for the present study was conducted between March 10, 2025, and February 19, 2026. Interventions: Participants were randomized to oral bempedoic acid, 180 mg, or placebo daily. Main Outcomes and Measures: The main outcome for this analysis was the time to first occurrence of VTE (composite of deep vein thrombosis or pulmonary embolism). The occurrences of deep vein thrombosis and pulmonary embolism were also assessed. Results: A total of 13 970 participants (mean [SD] age, 65.5 [9.0] years; 6740 [48.2%] female) were randomized, 6992 to bempedoic acid and 6978 to placebo. At the time of randomization, 275 participants (2.0%) had a history of VTE, and 1219 (8.7%) were receiving systemic anticoagulation. The participants were followed up for a median (IQR) of 40.6 (37.1-46.2) months. A total of 106 VTE events occurred (39 in the bempedoic acid group and 67 in the placebo group; hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P = .006). Findings were consistent for deep vein thrombosis (HR, 0.56; 95% CI, 0.31-0.996; P = .045) and pulmonary embolism (HR, 0.61; 95% CI, 0.37-0.996; P = .046). Conclusions and Relevance: Treatment with bempedoic acid among participants with statin intolerance at high risk for or with established cardiovascular disease was associated with a reduced risk of VTE. Trial Registration: ClinicalTrials.gov Identifier: NCT02993406.