Efficacy and safety of alirocumab in patients with established atherosclerotic vascular disease before the first cardiovascular event: Pooled analysis of phase 3 ODYSSEY studies

BACKGROUND: This post hoc analysis aimed to determine the efficacy and safety of alirocumab vs placebo or ezetimibe in patients with established atherosclerotic cardiovascular disease (ASCVD), but without previous acute coronary syndrome (ACS; myocardial infarction/unstable angina) or stroke. METHODS: Data were pooled from 12 phase 3 ODYSSEY studies with alirocumab. Adults with established ASCVD, without prior ischemic event (ACS or stroke) were included. Data were analyzed in 3 pools: pool 1 (alirocumab 75/150 mg once every 2 weeks [Q2W] vs ezetimibe), and pools 2 and 3 (alirocumab 75/150 mg Q2W or 150 mg Q2W, respectively, vs placebo). Primary objectives were percentage change in calculated low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 24 and percentage of patients with treatment-emergent adverse events (TEAEs). RESULTS: Overall, 963 patients were identified with ASCVD (without previous ACS or stroke). At baseline, mean calculated LDL-C levels ranged from 112.0 to 123.5 mg/dL across all pools. Alirocumab resulted in a significantly greater reduction in LDL-C levels at week 24 (pool 1: 51.5% reduction; pool 2: 47.8% reduction; pool 3: 60.9% reduction; P < .0001 for all), vs ezetimibe and placebo across all pools. The percentage of patients who experienced TEAEs was similar in the alirocumab and comparator arms (pool 1: 74.8% for alirocumab and 76.5% for ezetimibe; pools 2 and 3: 81.4% for alirocumab and 78.9% for placebo). CONCLUSION: Among patients with ASCVD without previous ACS or stroke, alirocumab significantly reduced calculated LDL-C levels vs controls and was well tolerated.