Bempedoic acid versus Ezetimibe added to Statin Therapy: Cardiovascular Outcomes in the Real-World – The BEYOND-REAL Study

BACKGROUND Residual atherosclerotic cardiovascular disease (ASCVD) risk remains common among adults treated with moderate-intensity statins, necessitating nonstatin therapy. Ezetimibe is the preferred first-line oral nonstatin therapy. However, bempedoic acid is emerging as an alternative, particularly in patients with statin intolerance. Cardiovascular outcomes with bempedoic acid among patients receiving moderate-intensity statins in routine care are not well-established. OBJECTIVE To compare cardiovascular outcomes associated with bempedoic acid vs ezetimibe when added to background moderate-intensity statin therapy in the real world. METHODS This retrospective cohort study used the TriNetX global federated health research network. Adults aged 18 years or older receiving moderate-intensity statin therapy with add-on bempedoic acid or ezetimibe were included. The primary outcome was a composite of stroke, myocardial infarction, ischemic heart disease, new-onset heart failure, or peripheral artery disease. Risk ratios (RRs) with 95% CIs were calculated. RESULTS After matching, 6706 patients were included (n = 3353 per cohort). Bempedoic acid was associated with a significantly lower risk of the composite outcome compared with ezetimibe (16.7% vs 22.8%; RR: 0.73; 95% CI: 0.63-0.84). All individual cardiovascular endpoints favored bempedoic acid. Low-density lipoprotein cholesterol (LDL-C) reduction was greater with ezetimibe. CONCLUSION Among adults on moderate-intensity statins, bempedoic acid was associated with significantly lower cardiovascular event rates compared with ezetimibe, despite smaller LDL-C reductions. These findings complement Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes and suggest greater ASCVD risk-reducing potential for bempedoic acid than currently reflected in clinical guidelines.