ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes with Alirocumab after an ACS
2018, Alirocumab after Acute Coronary Syndrome, ACC
ODYSSEY Outcomes Trial Summary
ODYSSEY OUTCOMES trial was a randomized, multicenter (1315 sites; 57 countries), placebo control, industry sponsored clinical trial to investigate the efficacy and safety of alirocumab (a PCSK9 inhibitor) in patients with an ACS in the preceding 1-12 months, who had inadequate control of lipids (LDL-C >=70mg/dl, or Non-HDL-C >=100mg/dl, or Apolipoprotein B >=80 mg/dl) despite of intensive or maximally tolerated statin therapy. These patients were >40 years of age, and did not have uncontrolled HTN, NYHA class III or IV HF, history of hemorrhagic stroke, fasting TGL>400 mg/dl, AST or ALT>3 x of normal, CK >3 x normal, eGFR< 30ml/min/1.73m2and hepatitis B or C. 18,924 patients were randomized after a run-in period of 2-16 weeks on high intensity or maximally tolerated dose of statin if they met at least one lipid entry criteria. Patients received every other week subcutaneous alirocumab or placebo. Alirocumab dose was adjusted (75or 150 mg) to target LDL-C levels to 25-50 mg/dl (but levels as low as 15 mg/dl were acceptable). Mean age of patients was 58 years, 25% were female, 35% had STEMI, 49% had NSTEMI, 93% met LDL-C lipid entry criteria, and 89% were on high-intensity statin. With alirocumab, LDL-C levels reduced by >50% (which occurred early on and was sustained). At 4 years, primary efficacy outcome of MACE [composite of coronary heart disease (CHD) death, non-fatal MI, ischemic stroke, and unstable angina requiring hospitalization]was significantly lower with alirocumab [9.5 % vs 11.1% in (HR 0.85; P 0.0003)]. Other than CHD death, all other components of MACE were statistically lower as well. Also, all-cause death was lower with alirocumab (3.5% vs 4.1%; HR 0.85).In the prespecified subgroups, patients with LDL-C >=100 mg/dl derived the maximum benefit with alirocumab. No safety signals with alirocumab, specifically no increase in neurocognitive disorder or hemorrhagic stroke; except higher local injection site reaction.
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