TY - JOUR
T1 - Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events The ODYSSEY OUTCOMES Trial
AU - Szarek, Michael
AU - White, Harvey D.
AU - Schwartz, Gregory G.
AU - Alings, Marco
AU - Bhatt, Deepak L.
AU - Bittner, Vera A.
AU - Diaz, Rafael
AU - Edelberg, Jay M.
AU - Goodman, Shaun G.
AU - Hanotin, Corinne
AU - Harrington, Robert A.
AU - Jukema, J. Wouter
AU - Kimura, Takeshi
AU - Kiss, Robert Gabor
AU - Lecorps, Guillaume
AU - Mahaffey, Kenneth W.
AU - Moryusef, Angele
AU - Pordy, Robert
AU - Roe, Matthew T.
AU - Tricoci, Pierluigi
AU - Xavier, Denis
AU - Zeiher, Andreas M.
AU - Steg, Gabriel
AU - ODYSSEY OUTCOMES Committees and Investigators
A2 - Clemmensen, Peter
A2 - Gislason, Gunnar
A2 - Larsen, John
A2 - Davidsen, Flemming
A2 - Videbaek, Lars
A2 - Andersen, Dorthe
PY - 2019/2/5
Y1 - 2019/2/5
N2 - 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.
AB - 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.
KW - acute coronary syndrome
KW - alirocumab
KW - total events
KW - Follow-Up Studies
KW - Humans
KW - Middle Aged
KW - Antibodies, Monoclonal/therapeutic use
KW - Male
KW - Antibodies, Monoclonal, Humanized
KW - Acute Coronary Syndrome/drug therapy
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
KW - Female
KW - Aged
KW - Drug Therapy, Combination
U2 - 10.1016/j.jacc.2018.10.039
DO - 10.1016/j.jacc.2018.10.039
M3 - Journal article
C2 - 30428396
SN - 0735-1097
VL - 73
SP - 387
EP - 396
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 4
ER -