J Wouter Jukema1, Michael Szarek2, Laurien E Zijlstra3, H Asita de Silva4, Deepak L Bhatt5, Vera A Bittner6, Rafael Diaz7, Jay M Edelberg8, Shaun G Goodman9, Corinne Hanotin10, Robert A Harrington11, Yuri Karpov12, Angèle Moryusef8, Robert Pordy13, Juan C Prieto14, Matthew T Roe15, Harvey D White16, Andreas M Zeiher17, Gregory G Schwartz18, P Gabriel Steg19. 1. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: j.w.jukema@lumc.nl. 2. State University of New York, Downstate School of Public Health, Brooklyn, New York. 3. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 4. Clinical Trials Unit, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka. 5. Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. 6. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama. 7. Latinoamerican Cardiological Studies, Cardiovascular Institute of Rosario, Rosario, Argentina. 8. Sanofi, Bridgewater, New Jersey. 9. Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 10. Sanofi, Paris, France. 11. Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California. 12. Russian Cardiological Scientific-Productive Complex, Moscow, Russian Federation. 13. Regeneron Pharmaceuticals, Inc., Tarrytown, New York. 14. University of Chile Clinical Hospital, Santiago, Chile. 15. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. 16. Green Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand. 17. Department of Medicine III, Goethe University, Frankfurt am Main, Germany. 18. Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado. 19. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris and Paris Diderot University, Sorbonne Paris Cité, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom.
Abstract
BACKGROUND:Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. OBJECTIVES: This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS: Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. RESULTS: Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). CONCLUSIONS: In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402).
RCT Entities:
BACKGROUND:Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. OBJECTIVES: This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. METHODS:Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. RESULTS: Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). CONCLUSIONS: In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402).
Authors: Maciej Banach; Paweł Burchardt; Krzysztof Chlebus; Piotr Dobrowolski; Dariusz Dudek; Krzysztof Dyrbuś; Mariusz Gąsior; Piotr Jankowski; Jacek Jóźwiak; Longina Kłosiewicz-Latoszek; Irina Kowalska; Maciej Małecki; Aleksander Prejbisz; Michał Rakowski; Jacek Rysz; Bogdan Solnica; Dariusz Sitkiewicz; Grażyna Sygitowicz; Grażyna Sypniewska; Tomasz Tomasik; Adam Windak; Dorota Zozulińska-Ziółkiewicz; Barbara Cybulska Journal: Arch Med Sci Date: 2021-11-08 Impact factor: 3.318
Authors: Mohammad Alkhalil; Michał Kuzemczak; Nicholas Whitehead; Charalampos Kavvouras; Vladimír Džavík Journal: J Am Heart Assoc Date: 2021-02-15 Impact factor: 5.501