Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic
cardiovascular events. We sought to determine whether alirocumab, a human monoclonal
antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular
outcomes after an acute coronary syndrome in patients receiving high-intensity statin
therapy.We conducted a multicenter, randomized, double-blind, placebo-controlled trial
involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier,
had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter
(1.8 mmol per liter), a non-high-density lipoprotein cholesterol level of at least
100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least
80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or
at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab
subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients)
every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target
an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter).
The primary end point was a composite of death from coronary heart disease, nonfatal
myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring
hospitalization.The median duration of follow-up was 2.8 years. A composite primary
end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052
patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval
[CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group
and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73
to 0.98). The absolute benefit of alirocumab with respect to the composite primary
end point was greater among patients who had a baseline LDL cholesterol level of 100
mg or more per deciliter than among patients who had a lower baseline level. The incidence
of adverse events was similar in the two groups, with the exception of local injection-site
reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).Among patients
who had a previous acute coronary syndrome and who were receiving high-intensity statin
therapy, the risk of recurrent ischemic cardiovascular events was lower among those
who received alirocumab than among those who received placebo. (Funded by Sanofi and
Regeneron Pharmaceuticals; ODYSSEY OUTCOMES ClinicalTrials.gov number, NCT01663402
.).
