Vera A Bittner1, Michael Szarek2, Philip E Aylward3, Deepak L Bhatt4, Rafael Diaz5, Jay M Edelberg6, Zlatko Fras7, Shaun G Goodman8, Sigrun Halvorsen9, Corinne Hanotin10, Robert A Harrington11, J Wouter Jukema12, Virginie Loizeau10, Patrick M Moriarty13, Angèle Moryusef6, Robert Pordy14, Matthew T Roe15, Peter Sinnaeve16, Sotirios Tsimikas17, Robert Vogel18, Harvey D White19, Doron Zahger20, Andreas M Zeiher21, Ph Gabriel Steg22, Gregory G Schwartz18. 1. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: vbittner@uab.edu. 2. State University of New York, Downstate School of Public Health, Brooklyn, New York. 3. South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, South Australia, Australia. 4. Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. Electronic address: https://twitter.com/DLBHATTMD. 5. Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina. 6. Sanofi, Bridgewater, New Jersey. 7. Division of Medicine, Department of Vascular Medicine, Preventive Cardiology Unit, University Medical Centre Ljubljana, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. 8. Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 9. Department of Cardiology, Oslo University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway. 10. Sanofi, Paris, France. 11. Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California. 12. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. 13. Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, Kansas. 14. Regeneron Pharmaceuticals Inc., Tarrytown, New York. 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. Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium; University of Leuven, Leuven, Belgium. 17. Division of Cardiovascular Medicine, University of California San Diego, La Jolla, California. 18. Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado. 19. Green Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand. 20. Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. 21. Department of Medicine III, Goethe University, Frankfurt am Main, Germany. 22. Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom. Electronic address: https://twitter.com/gabrielsteg.
Abstract
BACKGROUND:Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). METHODS: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. RESULTS:Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). CONCLUSIONS:Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
RCT Entities:
BACKGROUND:Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). METHODS: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. RESULTS: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). CONCLUSIONS: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
Authors: Nishant P Shah; Neha J Pajidipati; Robert W McGarrah; Ann Marie Navar; Sreekanth Vemulapalli; Michael A Blazing; Svati H Shah; Adrian F Hernandez; Manesh R Patel Journal: Am J Cardiol Date: 2020-04-07 Impact factor: 2.778
Authors: Brian A Bergmark; Michelle L O'Donoghue; Sabina A Murphy; Julia F Kuder; Marat V Ezhov; Richard Ceška; Ioanna Gouni-Berthold; Henrik K Jensen; S Lale Tokgozoglu; François Mach; Kurt Huber; Zbigniew Gaciong; Basil S Lewis; Francois Schiele; J Wouter Jukema; Terje R Pedersen; Robert P Giugliano; Marc S Sabatine Journal: JAMA Cardiol Date: 2020-06-01 Impact factor: 14.676