Trial Reference
Schwartz GG, Steg PG, Szarek M, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular
Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107.
Expert Comment
Daniel Lighezan, Vlad Ivan, Roxana Buzas
Title
Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome – ODYSSEY OUTCOMES: a multi-center, randomized, double-blind, placebo-con-trolled trial.
Background
Recurrent ischemic acute coronary events are a known fact in patients with a first such event with increase in mortality and morbidity. A new human monoclonal antibody directed towards proprotein convertase subtilisin–kexin type 9 (PCSK9) was tested for beneficial outcomes in patients after acute coronary syndromes who also received high potency statins. Under the concept “the lower, the better” a lower level of LDL cholesterol should in theory reduce the cardiovascular risk. To further prove this theory a new study was devised, in which a monoclonal antibody directed against the PCSK9, whose role is to promote the degradation of LDL cholesterol receptors.
ODYSSEY OUTCOMES study was a multicenter, randomized, double-blind, placebo-controlled trial with an enrolment of 18924 patients with a previous acute coronary event in the past 1 to 12 months, with a LDL cholesterol of at least 70mg/dl or apolipoprotein B level of at least 80mg/dl or non-HDL cholesterol lipoproteins of at least 100mg/dl. There was also a requirement that patients should receive a high potency statin or a maximum tolerated dose. The antibody directed against the PCSK9 was named alirocumab and patients received every two weeks either a 75mg dose of alirocumab or matching placebo. The entire lot was divided equally in 2 groups of 9462 patients. The LDL cholesterol was targeted to levels between 25-50mg. The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
Conclusion
The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower base-line level. The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo. The Kaplan–Meier probability estimate at 4 years was 12.5% in the alirocumab group and 14.5% in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001).
This study brings another proof that the lower the levels of LDL cholesterol the better are the outcomes, with the highest being in those with a more pronounced reduction in the LDL cholesterol levels.