Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events: The ODYSSEY OUTCOMES Trial

ODYSSEY OUTCOMES Committees and Investigators

Research output: Article

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalJournal of the American College of Cardiology
Volume73
Issue number4
DOIs
Publication statusPublished - febr. 5 2019

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

Keywords

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events : The ODYSSEY OUTCOMES Trial. / ODYSSEY OUTCOMES Committees and Investigators.

    In: Journal of the American College of Cardiology, Vol. 73, No. 4, 05.02.2019, p. 387-396.

    Research output: Article

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    title = "Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events: The ODYSSEY OUTCOMES Trial",
    abstract = "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.",
    keywords = "acute coronary syndrome, alirocumab, total events",
    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 Chiang, {Chern En} 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 R. Kiss 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 Steg, {Ph Gabriel}",
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    TY - JOUR

    T1 - Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events

    T2 - 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, R.

    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 - Steg, Ph Gabriel

    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

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    U2 - 10.1016/j.jacc.2018.10.039

    DO - 10.1016/j.jacc.2018.10.039

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    JO - Journal of the American College of Cardiology

    JF - Journal of the American College of Cardiology

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