Long‐Term Efficacy, Safety, and Tolerability of Alirocumab in 8242 Patients Eligible for 3 to 5 Years of Placebo‐Controlled Observation in the ODYSSEY OUTCOMES Trial

ipid-lowering therapy is ordinarily a long-term intervention to reduce cardiovascular risk.Yet, evaluation of long-term efficacy and safety of lipidlowering therapies is often limited by the duration of randomized clinical trials.The ODYSSEY OUTCOMES trial compared alirocumab, a monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), with placebo in 18 924 patients with a recent acute coronary syndrome followed up for up to 5 years.Over a median follow-up of 2.8 years, alirocumab lowered low-density lipoprotein cholesterol from a median 2.3 to 1.0 mmol/L at 4 months, reduced major adverse cardiovascular events (MACEs), 1 was associated with fewer deaths, 2 and had no excess of adverse events (AEs) except for mild-to-moderate local injection-site reactions.1 However, the efficacy and safety of alirocumab among patients eligible for longer follow-up have not been fully explored.The current post hoc analyses describe the efficacy, safety, and tolerability of alirocumab versus placebo in a prespecified subgroup 2 of patients eligible for ≥3 years of follow-up (ie, randomized ≥3 years before the common study end date).At each participating site, the study was approved by the responsible institutional review committee, and subjects gave informed consent.Hazard ratios (HRs) were calculated using Cox regression models, and P values were obtained using log-rank tests.Analyses were stratified by geographic region.Two assessments were performed for both the MACE and cardiovascular death end points to ensure that the proportional hazards model assumptions over time were met: log{-log[S(t)]} versus log[time] (identifying parallel curves) and interaction treatment×time (P interaction =0.19 for MACE, and P interaction =0.43 for cardiovascular death).