Alirocumab in patients with polyvascular disease and recent acute coronary syndrome: ODYSSEY OUTCOMES Trial.

Abstract

BACKGROUND: Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACE) and death. The impact of lipid-lowering by proprotein convertase subtilisin−kexin type 9 (PCSK9) inhibition in such patients is undetermined. OBJECTIVES: This pre-specified analysis from ODYSSEY OUTCOMES determined whether polyvascular disease (polyVD) influenced risks of MACE and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS: Patients were randomized to alirocumab or placebo 1−12 months after ACS. The primary MACE endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint.RESULTS: Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyVD in two beds (coronary and peripheral artery or cerebrovascular), and 149 had polyVD in three beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACE by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, corresponding absolute risk reduction (ARR [95% confidence interval]) was 1.4% (0.6, 2.3), 1.9% (−2.4%, 6.2%), and 13.0% (−2.0, 28.0). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; ARR with alirocumab was 0.4% (−0.1, 1.0), 1.3% (−1.8%, 4.3%), and 16.2% (5.5, 26.8). CONCLUSION: In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyVD is associated with high risks of MACE and death. The large absolute reductions in those risks with alirocumab are a potential benefit for this population.