Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events in the ODYSSEY OUTCOMES Trial

ODYSSEY OUTCOMES Committees and Investigators, Alessandro Salvioni

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The ODYSSEY OUTCOMES 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.

Original languageEnglish
JournalJournal of the American College of Cardiology
DOIs
Publication statusE-pub ahead of print - Oct 27 2018

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Acute Coronary Syndrome
Cause of Death
Placebos
Confidence Intervals
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Unstable Angina
alirocumab
Hospitalization
Ischemia
Heart Failure
Stroke
Myocardial Infarction
Therapeutics

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Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events in the ODYSSEY OUTCOMES Trial. / ODYSSEY OUTCOMES Committees and Investigators ; Salvioni, Alessandro.

In: Journal of the American College of Cardiology, 27.10.2018.

Research output: Contribution to journalArticle

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title = "Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events in the ODYSSEY OUTCOMES Trial",
abstract = "BACKGROUND: The ODYSSEY OUTCOMES 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.",
author = "{ODYSSEY OUTCOMES Committees and Investigators} and Michael Szarek and White, {Harvey D} and Schwartz, {Gregory G} and Marco Alings and Bhatt, {Deepak L} and Bittner, {Vera A} and Chern-En Chiang and Rafael Diaz and Edelberg, {Jay M} and Goodman, {Shaun G} and Corinne Hanotin and Harrington, {Robert A} and Jukema, {J Wouter} and Takeshi Kimura and Kiss, {Robert Gabor} and Guillaume Lecorps and Mahaffey, {Kenneth W} and Ang{\`e}le Moryusef and Robert Pordy and Roe, {Matthew T} and Pierluigi Tricoci and Denis Xavier and Zeiher, {Andreas M} and Alessandro Salvioni and Steg, {Ph Gabriel}",
note = "Copyright {\circledC} 2018. Published by Elsevier Inc.",
year = "2018",
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doi = "10.1016/j.jacc.2018.10.039",
language = "English",
journal = "Journal of the American College of Cardiology",
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T1 - Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events in the ODYSSEY OUTCOMES Trial

AU - ODYSSEY OUTCOMES Committees and Investigators

AU - Szarek, Michael

AU - White, Harvey D

AU - Schwartz, Gregory G

AU - Alings, Marco

AU - Bhatt, Deepak L

AU - Bittner, Vera A

AU - Chiang, Chern-En

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, Angèle

AU - Pordy, Robert

AU - Roe, Matthew T

AU - Tricoci, Pierluigi

AU - Xavier, Denis

AU - Zeiher, Andreas M

AU - Salvioni, Alessandro

AU - Steg, Ph Gabriel

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2018/10/27

Y1 - 2018/10/27

N2 - BACKGROUND: The ODYSSEY OUTCOMES 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 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.

U2 - 10.1016/j.jacc.2018.10.039

DO - 10.1016/j.jacc.2018.10.039

M3 - Article

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

ER -