Clinical Efficacy and Safety of Alirocumab after Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score-Matched Analysis of the ODYSSEY OUTCOMES Trial.

Background: Recent international guidelines have lowered recommended target levels of low-density lipoprotein-cholesterol (LDL-C) for patients at very high risk for major adverse cardiovascular events (MACE). However, uncertainty persists whether additional benefit results from achieved LDL-C levels below conventional targets. Inferences from prior analyses are limited because patients who achieve lower versus higher LDL-C on lipid-lowering therapy differ in other characteristics prognostic for MACE and because few achieved very low LDL-C levels. To overcome these limitations, we performed a propensity score matching (PSM) analysis of the ODYSSEY OUTCOMES trial which compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) receiving intensive or maximum-tolerated statin treatment. Methods: Patients on alirocumab were classified in prespecified strata of LDL-C achieved at 4 months of treatment: 50 mg/dL (n=2197). For each stratum, MACE (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) after month 4 was compared in patients receiving placebo with similar baseline characteristics and adherence, using 1:1 PSM. Results: Across achieved LDL-C strata of the alirocumab group patients differed by baseline LDL-C, lipoprotein(a), use of intensive statin therapy, study medication adherence, and other demographic, medical history, biometric, and laboratory criteria. After PSM, characteristics were similar in corresponding patients of the alirocumab and placebo groups. Treatment hazard ratio (HR), 95% confidence interval (CI), and absolute risk reduction (ARR, number per 100 patient-years) for MACE were similar in those with achieved LDL-C 50 mg/dL had poorer adherence and derived less benefit (HR, 0.87; 95% CI, 0.73 to 1.04; ARR, 0.62). No safety concerns were associated with a limited period of LDL-C levels <15 mg/dL. Conclusions: After accounting for differences in baseline characteristics and adherence, patients treated with alirocumab who achieved LDL-C levels <25 mg/dL did not appear to derive further reduction in the risk of MACE compared to those who achieved LDL-C levels of 25-50 mg/dL. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT01663402.