Reduced risk of MACE with PCSK9 inhibitor in patients with ACS
The ODYSSEY OUTCOMES trial (n=18,924) met its primary endpoint, showing that alirocumab significantly reduced the risk of major adverse cardiovascular events (MACE) in patients who had suffered an acute coronary syndrome (ACS), which included a myocardial infarction (MI) or unstable angina. MACE occurred in 903 patients (9.5%) in the alirocumab group and in 1,052 patients (11.1%) in the placebo group (HR: 0.85, 95%C: 0.78-0.93, P<0.001).
Death from any cause was less frequent among alirocumab-treated patients. Alirocumab was associated with a 15% lower risk of death; death occurred in 334 (3.5%) patients in the alirocumab group and 392 (4.1%) patients in the placebo group (HR: 0.85, 95%CI: 0.73-0.98).
Data according to subgroups of baseline LDL-c levels showed that patients with higher LDL-c at baseline (at least 100 mg/dL) were at greater risk of MACE, as well as other secondary endpoints, including death. Moreover, the greater risk-reduction occurred in this category of patients: in the alirocumab group MACE was reduced by 24% (HR: 0.76, 95%CI: 0.65-0.87) and death from any cause was 29% lower (HR:0.71, 95%CI: 0.56-0.90) compared to placebo. Adverse events were similar between groups, except for injection site reactions (alirocumab: 3.8%, placebo: 2.1%).
ODYSSEY OUTCOMES assessed the effect of alirocumab on the occurrence of MACE in patients who had experienced an ACS between 1-12 months (median 2.6 months) before enrolling in the trial, and who were already on intensive or maximally-tolerated statin treatment. Patients were randomized to receive alirocumab (n=9,462) or placebo (n=9,462) and were assessed for a median of 2.8 years, with some patients being treated for up to five years. Approximately 90% of patients were on a high-intensity statin.
MACE, the primary endpoint, was a composite of death from coronary heart disease, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
The trial was designed to maintain patients' LDL-c levels between 25-50 mg/dL, using two different doses of alirocumab (75 mg and 150 mg). Alirocumab treated patients started the trial on 75 mg every 2 weeks and switched to 150 mg every 2 weeks if their LDL-c levels remained above 50 mg/dL (n=2,615). Some patients who switched to 150 mg switched back to 75 mg if their LDL-c fell below 25 mg/dL (n=805), and patients who experienced two consecutive LDL-c measurements below 15 mg/dL while on the 75 mg dose (n=730) stopped active alirocumab therapy for the remainder of the trial.
Additional analyses of the ODYSSEY OUTCOME trial, including mortality, will be presented at the American Heart Association Scientific Sessions 2018.