Odyssey Outcomes - PVD Sub-analysis

This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy.

The trial was a randomized, double-blind, placebo-controlled comparison of alirocumab or placebo in patients with an ACS (myocardial infarction or unstable angina) 1–12months before randomization. Qualifying patients had persistent dyslipidemia [LDL-C≥ 70mg/dL (1.81mmol/L), non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100mg/dL (2.59mmol/L), or apolipoprotein B≥ 80mg/dL despite treatment with atorvastatin 40–80 mg daily, rosuvastatin 20–40mg daily, or the maximum-tolerated dose of one of these statins.

Participants were randomly assigned (1:1) to receive alirocumab 75mg or matching placebo subcutaneously every 2weeks. In this analysis, 3 subgroups of patients with recent ACS were defined on the basis of the distribution of other evident vascular disease: 1) monovascular disease (CAD without known PAD or CeVD); 2) polyvascular disease in 2 vascular beds (CAD and either PAD or CeVD); and 3) polyvascular disease in 3 vascular beds (CAD with both PAD and CeVD).

The primary outcome was a composite of MACE, including death due to coronary heart disease, non-fatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. Death from any cause was a secondary outcome.

A total of 18 924 patients underwent randomization; Of these, 9462 were assigned to alirocumab and 9462 to placebo with a median (quartile 1, quartile 3) follow-up of 2.8 years (2.3, 3.4 years). Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%).

Patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients.