Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events The ODYSSEY OUTCOMES Trial
Metadatos
Mostrar el registro completo del ítemEditorial
Elsevier
Fecha
2019-01-28Referencia bibliográfica
Szarek et al. Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events The ODYSSEY OUTCOMES Trial. J Am Coll Cardiol 2019;73:387–96 [https://doi.org/10.1016/j.jacc.2018.10.039]
Resumen
BACKGROUND The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome
During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or
maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the
first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths.
OBJECTIVES This pre-specified analysis determined the extent to which alirocumab reduced total (first and
subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES.
METHODS Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven
coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated,
linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An
association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model
provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death.
RESULTS With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or
deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events
(hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval:
0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk.
CONCLUSIONS In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented
with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a
more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS.