BACKGROUND: Obesity and hypercholesterolemia independently increase cardiovascular disease risk. This analysis evaluated the efficacy and safety of bempedoic acid in people with obesity participating in the CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL-Inhibiting Regimen) Outcomes trial. METHODS: CLEAR Outcomes randomized 13 970 patients to daily bempedoic acid 180 mg or placebo. Exploratory outcomes including major adverse cardiovascular events-4 (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization), low-density lipoprotein cholesterol, hs-CRP (high-sensitivity C-reactive protein), weight change, and safety were assessed over a median of 40.7 months in 6177 patients with baseline body mass index ≥30 kg/m RESULTS: In people with obesity, bempedoic acid resulted in placebo-corrected reductions in low-density lipoprotein cholesterol of -22.5% and hs-CRP of -23.2% at 6 months. Bempedoic acid treatment resulted in a major adverse cardiovascular events-4 reduction of 23% (hazard ratio [HR], 0.77 [95% CI, 0.67-0.89]) versus placebo. Nonfatal and fatal MI were reduced by 32% (HR, 0.68 [95% CI, 0.53-0.86]), coronary revascularization was reduced by 24% (HR, 0.76 [95% CI, 0.63-0.92]), and fatal and nonfatal stroke were reduced by 36% (HR, 0.64 [95% CI, 0.45-0.89]) compared with placebo. At month 36, mean±SD change in weight from baseline was -2.3 (6.3) kg for bempedoic acid and -1.4 (6.1) kg for placebo. Adverse events were reported in 87.4% of bempedoic acid patients and 86.7% of placebo patients. The mean±SD change in uric acid at 6 months was 0.81 (1.26) mg/dL for bempedoic acid versus -0.04 (1.05) mg/dL for placebo. CONCLUSIONS: Among people with obesity, bempedoic acid reduced major adverse cardiovascular events, low-density lipoprotein cholesterol, and hs-CRP, with a safety profile consistent with previous reports. REGISTRATION: URL: https://www.clinicaltrials.gov
Unique Identifier: NCT02993406.