Lipoprotein(a) and the Effect of Alirocumab on Revascularization After Acute Coronary Syndrome

BACKGROUND: Many patients require revascularization after index acute coronary syndrome (ACS). Lipoprotein(a) is thought to play a pathogenic role in atherothrombosis. In ODYSSEY OUTCOMES, alirocumab reduced major adverse cardiovascular events after ACS, with greater reduction among those with higher lipoprotein(a) levels. We explored whether risk of revascularization after ACS was modified by the level of lipoprotein(a) and treatment with alirocumab or placebo. METHODS: In ODYSSEY OUTCOMES alirocumab was compared with placebo in 18,924 patients with ACS and elevated atherogenic lipoprotein levels despite optimized statin treatment. In this post hoc analysis, treatment effects are summarized using competing risks proportional hazard models. RESULTS: A total of 1559 (8.2%) patients had coronary, 204 (1.1%) had limb, and 40 (0.2%) had carotid revascularization. Alirocumab reduced coronary revascularization (2.8 vs 3.2 events per 100 patient-years; hazard ratio [HR], 0.88 [95% confidence interval (CI), 0.80-0.97]; P = 0.01) and any revascularization (3.2 vs 3.7 events per 100 patient-years; HR, 0.85 [95% CI, 0.78-0.94]; P = 0.001). Baseline lipoprotein(a) quartile was directly associated with risk of coronary or any revascularization in the placebo arm and inversely related to treatment HRs (all P for trend < 0.01). Alirocumab produced the greatest reduction of coronary revascularization in patients with baseline lipoprotein(a) in the top quartile (≥ 59.6 mg/dL; HR, 0.69 [95% CI, 0.57-0.84]), but no apparent reduction in the bottom quartile (HR, 1.00 [95% CI, 0.82-1.22]). Findings were similar for the effect of alirocumab on any revascularization. CONCLUSIONS: Alirocumab reduced revascularization rates after ACS. The risk of revascularization and reduction in that risk with alirocumab were greatest in patients with elevated lipoprotein(a) at baseline.