Treatment with alirocumab, a PCSK9 inhibitor, reduced cardiovascular outcomes and all-cause deaths by 15% in patients with acute coronary syndrome (ACS) and higher-than-ideal atherogenic lipoprotein levels despite intensive or maximally tolerated statin therapy in the ODYSSEY trial.
The ODYSSEY trial was a 3-year multicenter, randomized, double-blind, placebo-controlled trial involving almost 19,000 patients who had had a previous ACS within 1 month to 1 year before enrollment. Their LDL-cholesterol level was at least 70 mg/dL, non−HDL cholesterol level was at least 100 mg/dL or an apolipoprotein B level was at least 80 mg/dL; they were on statin therapy at a high-intensity dose or at the maximum tolerated dose.
Patients were randomized to biweekly injections of alirocumab or placebo. The dose could be uptitrated if LDL-cholesterol <50mg/dL was not achieved.
After 2.8 years, alirocumab significantly reduced cardiovascular (CV) death, myocardial infarction (MI), stroke, or hospitalization (primary end point) from 11.1% in the placebo group to 9.5% in the alirocumab group. Mortality was also reduced with alirocumab from 4.1% in placebo group down to 3.5% in the alirocumab group.
The benefits were greater among patients who had a baseline LDL-cholesterol of ≥100 mg/dL, where there was a 3.4% absolute risk reduction vs patients who had a lower baseline level. In that subgroup, you would only have to treat about 30 people to prevent a MACE event and there was a 1.7% reduction in mortality.
ODYSSEY Outcomes is the second outcomes trial with a PCSK9 inhibitor to show a reduction in LDL-C and cardiovascular endpoints. The earlier FOURIER trial, which used a fixed dose of the PCSK9 inhibitor evolocumab, showed no mortality advantages. Compared with FOURIER, the ODYSSEY Outcomes trial enrolled a higher-risk group of patients, had a longer duration of follow-up (ranging from two to five years), involved a different dosing strategy and had a slightly different primary endpoint
(Source: N Engl J Med. 2018;379:2097-210; Medscape, ACC News)