Abstract 9794: Factors Associated with Enhanced Low-Density Lipoprotein Cholesterol Lowering with Bempedoic Acid Among Patients Enrolled in Phase 3 Studies

Abstract

Bempedoic acid (BA) inhibits ATP-citrate lyase in the cholesterol synthesis pathway. In phase 3 studies, 12 weeks of BA lowered low-density lipoprotein cholesterol (LDL-C) levels compared with placebo by a mean of 17.8% among patients primarily receiving moderate- to high-intensity statin and by 24.5% among statin intolerant patients who were receiving low-dose or no statin. Cholesterol guidelines (Grundy et al. J Am Coll Cardiol . 2019;73:e285) categorize statins according to percent LDL-C lowering: high-intensity (≥ 50%), moderate-intensity (30-49%), and low-intensity (< 30%). We examined LDL-C lowering with BA similarly using pooled data from 4 phase 3 studies in patients on background maximally tolerated statins; 3488 (2321 BA, 1167 PBO) patients were included in the analysis. From baseline to week 12, BA lowered LDL-C levels comparable to that of a moderate- or high-intensity statin (≥ 30%) in 28.9% of patients; this degree of LDL-C lowering was observed in 50.9% of the patients not receiving background statin therapy (Table). A multivariate analysis showed that the absence of baseline statin use was associated with increased rates of achieving at least a 30% reduction in LDL-C with BA treatment (odds ratio [95% CI], 2.49 [1.94, 3.19; P < .0001). Further, being female, a history of diabetes, baseline ezetimibe use, and a higher baseline hsCRP level were also associated with at least a 30% reduction in LDL-C levels ( P < .01 for each). These findings suggest that 1) a significant proportion of patients initiating BA treatment may achieve LDL-C lowering comparable to moderate- or high-intensity statin therapy, especially among patients who cannot tolerate a statin, and 2) patients with hypercholesterolemia who are at higher risk for a cardiovascular event, including women and patients with a history of statin intolerance, diabetes, or higher baseline hsCRP levels, may also achieve enhanced LDL-C lowering with bempedoic acid.