Gregory G Schwartz1, Laurence Bessac2, Lisa G Berdan3, Deepak L Bhatt4, Vera Bittner5, Rafael Diaz6, Shaun G Goodman7, Corinne Hanotin2, Robert A Harrington8, J Wouter Jukema9, Kenneth W Mahaffey8, Angèle Moryusef2, Robert Pordy10, Matthew T Roe3, Tyrus Rorick3, William J Sasiela10, Cheerag Shirodaria11, Michael Szarek12, Jean-François Tamby2, Pierluigi Tricoci3, Harvey White13, Andreas Zeiher14, Philippe Gabriel Steg15. 1. University of Colorado School of Medicine, Denver, CO. Electronic address: Gregory.Schwartz@va.gov. 2. Sanofi-Aventis Recherche et Développement S.A., Paris, France; Sanofi-Aventis Recherche et Développement S.A., Bridgewater, NJ. 3. Duke Clinical Research Institute, Durham, NC. 4. Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 5. University of Alabama at Birmingham, Birmingham, AL. 6. Estudios Cardiológicos Latinoamérica, Rosario, Argentina. 7. Canadian VIGOUR Centre, University of Alberta, Toronto, Canada. 8. Stanford University, Stanford, CA. 9. Leiden University Medical Center, Leiden, the Netherlands. 10. Regeneron Therapeutics, Tarrytown, NY. 11. Covance, Inc.,Maidenhead, and Oxford University Hospitals NHS Trust, Oxford, United Kingdom. 12. State University of New York Downstate Medical Center, Brooklyn, NY. 13. Auckland City Hospital and University of Auckland, Auckland, New Zealand. 14. Johann Wolfgang Goethe University, Frankfurt, Germany. 15. Assistance Publique-Hôpitaux de Paris, INSERM U-1148, Université Paris Diderot, Paris, France.
Abstract
BACKGROUND: Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS. DESIGN: This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred. SUMMARY: ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS.
RCT Entities:
BACKGROUND: Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS. DESIGN: This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred. SUMMARY: ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS.
Authors: Seung Ho Lee; Huiyan Piao; Yong Chan Cho; Se-Na Kim; Goeun Choi; Cho Rim Kim; Han Bi Ji; Chun Gwon Park; Cheol Lee; Chong In Shin; Won-Gun Koh; Young Bin Choy; Jin-Ho Choy Journal: Proc Natl Acad Sci U S A Date: 2019-05-23 Impact factor: 11.205