ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab

Summary

Primary Objective: To compare the effect of alirocumab with placebo on the occurrence of cardiovascular (CV) events (composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, unstable angina (UA) requiring hospitalization) in participants who experienced an acute coronary syndrome (ACS) event 4 to 52 weeks prior to randomization and were treated with evidence-based medical and dietary management of dyslipidemia. Secondary Objectives: * To evaluate the effect of alirocumab on secondary endpoints (any CHD event , major CHD event, any CV event, composite of all cause mortality/non-fatal MI/non-fatal ischemic stroke, CHD deaths, CV deaths, all cause mortality). * To evaluate the safety and tolerability of alirocumab. * To evaluate the effect of alirocumab on lipid parameters.

Timeline

Start

2012-10

Primary completion

2018-01-23

Completion

2018-01-23

Publications

• Tsimikas S, Szarek M, Cobbaert CM, Romijn F, Jukema JW, Bhatt DL, Bittner VA, Diaz R, Fazio S, Garon G, Yuan C, Gong XM, Goodman SG, White HD, Witztum JL, Steg PG, Schwartz GG; ODYSSEY OUTCOMES Investigators. Oxidized Phospholipids, Lipoprotein(a), and Cardiovascular Outcomes After Acute Coronary Syndrome. Circulation. 2025 Dec 16;152(24):1666-1678. doi: 10.1161/CIRCULATIONAHA.125.073855. Epub 2025 Dec 1.
• Reijnders E, Bossuyt PM, Jukema JW, Ruhaak LR, Romijn FPHTM, Szarek M, Trompet S, Bhatt DL, Bittner VA, Diaz R, Fazio S, Stevanovic I, Goodman SG, Harrington RA, White HD, Steg PG, Schwartz GG, Cobbaert CM. Multiplex Apolipoprotein Panel Improves Cardiovascular Event Prediction and Cardiovascular Outcome by Identifying Patients Who Benefit From Targeted PCSK9 Inhibitor Therapy. Arterioscler Thromb Vasc Biol. 2025 Nov;45(11):2111-2123. doi: 10.1161/ATVBAHA.124.322336. Epub 2025 Sep 25.
• Geba GP, Mohammadi KA, Damask A, Paulding C, Lotta LA, Hindy G, Pordy R, Manvelian G, Shapiro MD, Bittner VA, Bhatt DL, Szarek M, Schwartz GG, Steg PG, Fazio S. Effect of PCSK9 Inhibition With Alirocumab in Patients With Probable Familial Hypercholesterolemia or Type III Hyperlipoproteinemia: Results From the ODYSSEY OUTCOMES Trial. J Am Heart Assoc. 2025 Sep 2;14(17):e041190. doi: 10.1161/JAHA.124.041190. Epub 2025 Aug 22.
• Steg PG, Szarek M, Jukema JW, Bhatt DL, Bittner VA, Diaz R, Fazio S, Garon G, Goodman SG, Harrington RA, White HD, Zeiher AM, Schwartz GG; ODYSSEY OUTCOMES Investigators. Relation of Low-Density Lipoprotein Cholesterol, High-Sensitivity C-Reactive Protein, and Lipoprotein(a) Each to Future Cardiovascular Events and Death After Acute Coronary Syndrome on High-Intensity Statin Therapy: An Analysis of the Placebo Arm of ODYSSEY OUTCOMES. Circulation. 2025 Apr 8;151(14):1047-1050. doi: 10.1161/CIRCULATIONAHA.124.071269. Epub 2025 Apr 7. No abstract available.
• Geba GP, Chen R, Talapatra K, Brackin T, Mohammadi KA, Pordy R, Manvelian G, Maron DJ, Schwartz GG, Szarek M, Steg PG, Fazio S. Alirocumab and chest pain after acute coronary syndrome: An analysis of ODYSSEY OUTCOMES. Am J Prev Cardiol. 2024 Nov 26;20:100900. doi: 10.1016/j.ajpc.2024.100900. eCollection 2024 Dec.
• Reijnders E, Romijn FPHTM, Arslan F, Georges JJJ, Pieterse MM, Schipper ER, Didden-Buitendijk S, Martherus-Bultman MC, Smit NPM, Diederiks NM, Treep MM, Jukema JW, Cobbaert CM, Ruhaak LR. Quality Assurance for Multiplex Quantitative Clinical Chemistry Proteomics in Large Clinical Trials. J Appl Lab Med. 2024 Nov 4;9(6):949-963. doi: 10.1093/jalm/jfae092.
• Zahger D, Schwartz GG, Du W, Szarek M, Bhatt DL, Bittner VA, Budaj AJ, Diaz R, Goodman SG, Jukema JW, Kiss RG, Harrington RA, Moriarty PM, Scemama M, Manvelian G, Pordy R, White HD, Zeiher AM, Fazio S, Geba GP, Steg PG; ODYSSEY OUTCOMES Investigators. Triglyceride Levels, Alirocumab Treatment, and Cardiovascular Outcomes After an Acute Coronary Syndrome. J Am Coll Cardiol. 2024 Sep 10;84(11):994-1006. doi: 10.1016/j.jacc.2024.06.035.
• Bittner VA, Schwartz GG, Bhatt DL, Chua T, De Silva HA, Diaz R, Goodman SG, Harrington RA, Jukema JW, McGinniss J, Pordy R, Garon G, Scemama M, White HD, Steg PG, Szarek M; ODYSSEY OUTCOMES Investigators. Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: a report from the ODYSSEY OUTCOMES study. J Clin Lipidol. 2024 Jul-Aug;18(4):e548-e561. doi: 10.1016/j.jacl.2024.04.122. Epub 2024 Apr 10.
• Lawler PR, Manvelian G, Coppi A, Damask A, Cantor MN, Ferreira MAR, Paulding C, Banerjee N, Li D, Jorgensen S, Attre R, Carey DJ, Krebs K, Milani L, Hveem K, Damas JK, Solligard E, Stender S, Tybjaerg-Hansen A, Nordestgaard BG, Hernandez-Beeftink T, Rogne T, Flores C, Villar J, Walley KR, Liu VX, Fohner AE, Lotta LA, Kyratsous CA, Sleeman MW, Scemama M, DelGizzi R, Pordy R, Horowitz JE, Baras A, Martin GS, Steg PG, Schwartz GG, Szarek M, Goodman SG. Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival From Sepsis. Crit Care Explor. 2023 Nov 8;5(11):e0997. doi: 10.1097/CCE.0000000000000997. eCollection 2023 Nov.
• Goodman SG, Steg PG, Poulouin Y, Bhatt DL, Bittner VA, Diaz R, Garon G, Harrington RA, Jukema JW, Manvelian G, Stipek W, Szarek M, White HD, Schwartz GG; ODYSSEY OUTCOMES Investigators. Long-Term Efficacy, Safety, and Tolerability of Alirocumab in 8242 Patients Eligible for 3 to 5 Years of Placebo-Controlled Observation in the ODYSSEY OUTCOMES Trial. J Am Heart Assoc. 2023 Sep 19;12(18):e029216. doi: 10.1161/JAHA.122.029216. Epub 2023 Sep 13. No abstract available.
• Szarek M, Reijnders E, Jukema JW, Bhatt DL, Bittner VA, Diaz R, Fazio S, Garon G, Goodman SG, Harrington RA, Ruhaak LR, Schwertfeger M, Tsimikas S, White HD, Steg PG, Cobbaert C, Schwartz GG; ODYSSEY OUTCOMES Investigators. Relating Lipoprotein(a) Concentrations to Cardiovascular Event Risk After Acute Coronary Syndrome: A Comparison of 3 Tests. Circulation. 2024 Jan 16;149(3):192-203. doi: 10.1161/CIRCULATIONAHA.123.066398. Epub 2023 Aug 26.
• Suc G, Schwartz GG, Goodman SG, Jukema JW, Manvelian G, Poulouin Y, Pordy R, Scemama M, Szarek M, Steg PG; ODYSSEY OUTCOMES Investigators. Effect of alirocumab on cataracts in patients with acute coronary syndromes. BMC Ophthalmol. 2023 Jun 16;23(1):279. doi: 10.1186/s12886-023-03012-1.
• Schwartz GG, Szarek M, Bhatt DL, Bittner VA, Bujas-Bobanovic M, Diaz R, Fazio S, Fras Z, Goodman SG, Harrington RA, Jukema JW, Manvelian G, Pordy R, Ray KK, Scemama M, White HD, Steg PG; ODYSSEY OUTCOMES Investigators. Transiently achieved very low LDL-cholesterol levels by statin and alirocumab after acute coronary syndrome are associated with cardiovascular risk reduction: the ODYSSEY OUTCOMES trial. Eur Heart J. 2023 Mar 5;44(16):1408-17. doi: 10.1093/eurheartj/ehad144. Online ahead of print.
• Hagstrom E, Steg PG, Szarek M, Bhatt DL, Bittner VA, Danchin N, Diaz R, Goodman SG, Harrington RA, Jukema JW, Liberopoulos E, Marx N, McGinniss J, Manvelian G, Pordy R, Scemama M, White HD, Zeiher AM, Schwartz GG; ODYSSEY OUTCOMES Investigators. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab. Circulation. 2022 Aug 30;146(9):657-672. doi: 10.1161/CIRCULATIONAHA.121.057807. Epub 2022 Jun 30.
• Landmesser U, McGinniss J, Steg PG, Bhatt DL, Bittner VA, Diaz R, Dilic M, Goodman SG, Jukema JW, Loy M, Pecin I, Pordy R, Poulsen SH, Szarek M, White HD, Schwartz GG; ODYSSEY OUTCOMES Investigators. Achievement of ESC/EAS LDL-C treatment goals after an acute coronary syndrome with statin and alirocumab. Eur J Prev Cardiol. 2022 Oct 20;29(14):1842-1851. doi: 10.1093/eurjpc/zwac107.
• Chiang CE, Schwartz GG, Elbez Y, Szarek M, Bhatt DL, Bittner VA, Diaz R, Erglis A, Goodman SG, Hagstrom E, Jukema JW, Liberopoulos E, Loy M, Pordy R, White HD, Simon T, Steg PG; ODYSSEY OUTCOMES Investigators. Alirocumab and Cardiovascular Outcomes in Patients With Previous Myocardial Infarction: Prespecified Subanalysis From ODYSSEY OUTCOMES. Can J Cardiol. 2022 Oct;38(10):1542-1549. doi: 10.1016/j.cjca.2022.05.021. Epub 2022 May 27.
• Ostadal P, Steg PG, Poulouin Y, Bhatt DL, Bittner VA, Chua T, Diaz R, Goodman SG, Huo Y, Jukema JW, Karpov Y, Pordy R, Scemama M, Szarek M, White HD, Schwartz GG; ODYSSEY OUTCOMES Investigators. Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol. 2022 May;10(5):330-340. doi: 10.1016/S2213-8587(22)00043-2. Epub 2022 Apr 1.
• Lopes RD, Guimaraes PO, Schwartz GG, Bhatt DL, Bittner VA, Budaj A, Dalby AJ, Diaz R, Goodman SG, Harrington RA, Jukema JW, Kiss RG, Loy M, Pordy R, Poulouin Y, Szarek M, White HD, Steg PG; ODYSSEY OUTCOMES Investigators. Effect of Alirocumab on Incidence of Atrial Fibrillation After Acute Coronary Syndromes: Insights from the ODYSSEY OUTCOMES Trial. Am J Med. 2022 Jul;135(7):915-918. doi: 10.1016/j.amjmed.2022.02.016. Epub 2022 Mar 14.
• Schwartz GG, Szarek M, Bittner VA, Diaz R, Goodman SG, Jukema JW, Landmesser U, Lopez-Jaramillo P, Manvelian G, Pordy R, Scemama M, Sinnaeve PR, White HD, Gabriel Steg P; ODYSSEY Outcomes Committees and Investigators. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. J Am Coll Cardiol. 2021 Aug 3;78(5):421-433. doi: 10.1016/j.jacc.2021.04.102.
• Diaz R, Li QH, Bhatt DL, Bittner VA, Baccara-Dinet MT, Goodman SG, Jukema JW, Kimura T, Parkhomenko A, Pordy R, Reiner Z, Roe MT, Szarek M, Tse HF, White HD, Zahger D, Zeiher AM, Schwartz GG, Steg PG; ODYSSEY OUTCOMES Committees and Investigators. Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial. Eur J Prev Cardiol. 2021 Mar 23;28(1):33-43. doi: 10.1177/2047487320941987. Epub 2020 Jul 27.
• Schwartz GG, Szarek M, Bittner VA, Bhatt DL, Diaz R, Goodman SG, Jukema JW, Loy M, Manvelian G, Pordy R, White HD, Steg PG; ODYSSEY OUTCOMES Committees and Investigators. Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment. Diabetes Care. 2021 May;44(5):1219-1227. doi: 10.2337/dc20-2842. Epub 2021 Mar 15.
• Schwartz GG, Gabriel Steg P, Bhatt DL, Bittner VA, Diaz R, Goodman SG, Jukema JW, Kim YU, Li QH, Manvelian G, Pordy R, Sourdille T, White HD, Szarek M; ODYSSEY OUTCOMES Committees and Investigators. Clinical Efficacy and Safety of Alirocumab After Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score-Matched Analysis of the ODYSSEY OUTCOMES Trial. Circulation. 2021 Mar 16;143(11):1109-1122. doi: 10.1161/CIRCULATIONAHA.120.049447. Epub 2021 Jan 13.
• Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
• Szarek M, Bittner VA, Aylward P, Baccara-Dinet M, Bhatt DL, Diaz R, Fras Z, Goodman SG, Halvorsen S, Harrington RA, Jukema JW, Moriarty PM, Pordy R, Ray KK, Sinnaeve P, Tsimikas S, Vogel R, White HD, Zahger D, Zeiher AM, Steg PG, Schwartz GG; ODYSSEY OUTCOMES Investigators. Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial. Eur Heart J. 2020 Nov 21;41(44):4245-4255. doi: 10.1093/eurheartj/ehaa649.
• Bhatt DL, Briggs AH, Reed SD, Annemans L, Szarek M, Bittner VA, Diaz R, Goodman SG, Harrington RA, Higuchi K, Joulain F, Jukema JW, Li QH, Mahaffey KW, Sanchez RJ, Roe MT, Lopes RD, White HD, Zeiher AM, Schwartz GG, Gabriel Steg P; ODYSSEY OUTCOMES Investigators. Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes: The ODYSSEY OUTCOMES Trial. J Am Coll Cardiol. 2020 May 12;75(18):2297-2308. doi: 10.1016/j.jacc.2020.03.029.
• Schwartz GG, Steg PG, Szarek M, Bittner VA, Diaz R, Goodman SG, Kim YU, Jukema JW, Pordy R, Roe MT, White HD, Bhatt DL; ODYSSEY OUTCOMES Committees and Investigators*. Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome: Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial. Circulation. 2020 May 19;141(20):1608-1617. doi: 10.1161/CIRCULATIONAHA.120.046524. Epub 2020 Mar 29.
• Bittner VA, Szarek M, Aylward PE, Bhatt DL, Diaz R, Edelberg JM, Fras Z, Goodman SG, Halvorsen S, Hanotin C, Harrington RA, Jukema JW, Loizeau V, Moriarty PM, Moryusef A, Pordy R, Roe MT, Sinnaeve P, Tsimikas S, Vogel R, White HD, Zahger D, Zeiher AM, Steg PG, Schwartz GG; ODYSSEY OUTCOMES Committees and Investigators. Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome. J Am Coll Cardiol. 2020 Jan 21;75(2):133-144. doi: 10.1016/j.jacc.2019.10.057.
• Szarek M, Steg PG, DiCenso D, Bhatt DL, Bittner VA, Budaj A, Diaz R, Goodman SG, Gotcheva N, Jukema JW, Pordy R, Roe MT, Sourdille T, White HD, Xavier D, Zeiher AM, Schwartz GG. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial. Circ Cardiovasc Qual Outcomes. 2019 Nov;12(11):e005858. doi: 10.1161/CIRCOUTCOMES.119.005858. Epub 2019 Nov 11.
• Jukema JW, Zijlstra LE, Bhatt DL, Bittner VA, Diaz R, Drexel H, Goodman SG, Kim YU, Pordy R, Reiner Z, Roe MT, Tse HF, Montenegro Valdovinos PC, White HD, Zeiher AM, Szarek M, Schwartz GG, Steg PG; ODYSSEY OUTCOMES Investigators. Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES. Circulation. 2019 Dec 17;140(25):2054-2062. doi: 10.1161/CIRCULATIONAHA.119.043826. Epub 2019 Nov 11.
• Roe MT, Li QH, Bhatt DL, Bittner VA, Diaz R, Goodman SG, Harrington RA, Jukema JW, Lopez-Jaramillo P, Lopes RD, Louie MJ, Moriarty PM, Szarek M, Vogel R, White HD, Zeiher AM, Baccara-Dinet MT, Steg PG, Schwartz GG. Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes. Circulation. 2019 Nov 5;140(19):1578-1589. doi: 10.1161/CIRCULATIONAHA.119.042551. Epub 2019 Sep 2.
• Goodman SG, Aylward PE, Szarek M, Chumburidze V, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Hanotin C, Harrington RA, Jukema JW, Kedev S, Letierce A, Moryusef A, Pordy R, Ramos Lopez GA, Roe MT, Viigimaa M, White HD, Zeiher AM, Steg PG, Schwartz GG; ODYSSEY OUTCOMES Committees and Investigators. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery. J Am Coll Cardiol. 2019 Sep 3;74(9):1177-1186. doi: 10.1016/j.jacc.2019.07.015.
• Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt DL, Bittner VA, Budaj AJ, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Loizeau V, Lopes RD, Moryusef A, Murin J, Pordy R, Ristic AD, Roe MT, Tunon J, White HD, Zeiher AM, Schwartz GG, Steg PG; ODYSSEY OUTCOMES Committees and Investigators. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Aug;7(8):618-628. doi: 10.1016/S2213-8587(19)30158-5. Epub 2019 Jul 1.
• Steg PG, Szarek M, Bhatt DL, Bittner VA, Bregeault MF, Dalby AJ, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Ostadal P, Parkhomenko A, Pordy R, Roe MT, Tricoci P, Vogel R, White HD, Zeiher AM, Schwartz GG. Effect of Alirocumab on Mortality After Acute Coronary Syndromes. Circulation. 2019 Jul 9;140(2):103-112. doi: 10.1161/CIRCULATIONAHA.118.038840. Epub 2019 May 23.
• Jukema JW, Szarek M, Zijlstra LE, de Silva HA, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Karpov Y, Moryusef A, Pordy R, Prieto JC, Roe MT, White HD, Zeiher AM, Schwartz GG, Steg PG; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial. J Am Coll Cardiol. 2019 Sep 3;74(9):1167-1176. doi: 10.1016/j.jacc.2019.03.013. Epub 2019 Mar 18.
• Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. Epub 2018 Nov 7.
• Schwartz GG, Bessac L, Berdan LG, Bhatt DL, Bittner V, Diaz R, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Mahaffey KW, Moryusef A, Pordy R, Roe MT, Rorick T, Sasiela WJ, Shirodaria C, Szarek M, Tamby JF, Tricoci P, White H, Zeiher A, Steg PG. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014 Nov;168(5):682-9. doi: 10.1016/j.ahj.2014.07.028. Epub 2014 Aug 7.

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