Bempedoic Acid Plus Ezetimibe and Carotid IMT: BENEFIT Pilot Observational Study

Abstract

Atherosclerosis is a chronic progressive disease and a leading cause of mortality, with low-density lipoprotein cholesterol (LDL-C) as a key causal factor. Bempedoic acid (BA) lowers LDL-C, but its effects on carotid intima-media thickness (IMT) and plaque features are unclear. To evaluate 12-month changes in LDL-C, carotid IMT, and plaque thickness after adding BA to background lipid-lowering therapy. Prospective, longitudinal, observational pilot study including patients with persistent dyslipidemia on ezetimibe and/or statins and/or PCSK9 inhibitors with a clinical indication for BA. Participants were analyzed as BA plus ezetimibe alone (BA-EZE) or BA plus ezetimibe with other lipid-lowering agents (BA-EZE-OTHER). Lipid profile was assessed at baseline, 6, and 12 months. Carotid color Doppler ultrasound measured common carotid IMT and plaque thickness. Analyses were performed in R. In the BA-EZE group (n = 21; 71.4% women; nonsmokers; no diabetes or PAD/CAD), LDL-C decreased from 124.3 ± 40.7 to 80.2 ± 20.4 mg/dL, and 81.8% achieved LDL-C targets at 12 months. IMT showed a decreasing trend over 12 months, independent of LDL-C target achievement. In the BA-EZE-OTHER group (n = 8; 25% women), LDL-C changed from 81.2 ± 36.3 to 59.7 ± 31.7 mg/dL, with no significant IMT change from baseline to 12 months (left IMT +0.082 mm, p = 0.569; right IMT −0.044 mm, p = 0.643). IMT did not differ at baseline but was lower in BA-EZE than in BA-EZE-OTHER at 12 months. BA therapy may reduce carotid IMT independently of LDL-C lowering, suggesting potential anti-atherosclerotic effects beyond cholesterol reduction. Larger studies are warranted.