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

BACKGROUND

Many patients require revascularization after an 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

ODYSSEY OUTCOMES compared alirocumab with placebo in 18 924 patients with ACS and elevated atherogenic lipoproteins despite optimized statin treatment. In this post hoc analysis, treatment effects are summarized by 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 versus 3.2 events per 100 patient-years; HR, 0.88 [95% CI, 0.80-0.97]; P=0.01) and any revascularization (3.2 versus 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 Ptrend <0.001). 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 after ACS. The risk of revascularization and reduction in that risk with alirocumab were greatest in patients with elevated lipoprotein(a) at baseline. (ODYSSEY OUTCOMES NCT01663402).