Schwartz GG, et al. - Researchers investigated the effect of alirocumab, a human monoclonal antibody to proprotein convertase subtilisin–kexin type 9 (PCSK9), on cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy. Compared to patients who received placebo, those receiving alirocumab displayed a lower risk of recurrent ischemic cardiovascular events among patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy.

Methods

• Researchers performed a multicenter, randomized, double-blind, placebo-controlled trial, including 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.
• They randomy assigned patients to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks.
• Under blinded conditions, they adjusted the dose of alirocumab to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter).
• A composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization was assessed as the primary end point.

Results

• The median duration of follow-up was 2.8 years.
• In 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group, researchers noted a composite primary end-point event (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001).
• In the alirocumab group and the placebo group, 334 patients (3.5%) and 392 patients (4.1%) died, respectively (hazard ratio, 0.85; 95% CI, 0.73 to 0.98).
• Patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter displayed greater absolute benefit of alirocumab with respect to the composite primary end point than patients who had a lower baseline level.
• The two groups had similar incidence of adverse events, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).