Reduced risk of MACE with PCSK9 inhibitor in patients with ACS
The ODYSSEY OUTCOMES trial met its primary safety endpoint, showing reduced risk of MACE with alirocumab in patients with ACS compared to placebo, which is dependent on baseline LDL-c levels.
News - Nov. 9, 2018The 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.