Clinical and Metabolic Effects of ATP Citrate Lyase Inhibition with Bempedoic Acid in Patients with Chronic Coronary Syndrome: A Real-World Translational Study

Background: Hepatic cholesterol synthesis inhibition is a cornerstone of atherosclerotic cardiovascular disease (ASCVD) prevention. Despite intensive lipid-lowering therapy, many very-high-risk patients with chronic coronary syndrome (CCS) fail to achieve recommended LDL-C targets. Bempedoic acid (BA), a liver-activated ATP citrate lyase (ACLY) inhibitor, suppresses cholesterol biosynthesis upstream of HMG-CoA reductase and may have metabolic and renal effects. Methods: We conducted a prospective, single-centre, real-world study including consecutive CCS patients with LDL-C ≥55 mg/dL despite stable intensive lipid-lowering therapy (high-intensity statin plus ezetimibe or PCSK9 inhibitor plus ezetimibe in statin-intolerant patients). BA 180 mg/day was added to background therapy. Lipid parameters, uric acid, and renal function were assessed at baseline and ≥8 weeks. Multivariable regression analyses identified predictors of LDL-C reduction and target attainment. Results: Among 118 patients with complete follow-up (mean age 62.4 ± 10.0 years; 79.2% male), BA reduced LDL-C by 22.8% (−16.36 mg/dL; p < 0.001), enabling 48.3% to achieve LDL-C < 55 mg/dL. Total and non–HDL cholesterol decreased significantly, whereas triglycerides and fasting glucose remained unchanged. HDL-C showed a modest reduction. Uric acid increased by 0.96 mg/dL without gout events, and renal function changes were small and clinically non-relevant. Higher historical untreated LDL-C and diabetes mellitus independently predicted greater LDL-C reduction; higher historical LDL-C and baseline uric acid predicted LDL-C goal attainment. Conclusions: ACLY inhibition with BA provides clinically meaningful LDL-C reduction in intensively treated CCS patients, revealing a cardiometabolic phenotype with proportional lipid responsiveness and modest urate changes. BA represents an effective translational strategy linking hepatic cholesterol metabolism to clinical lipid optimization in very-high-risk patients.