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Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome |
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| Author: | Bittner, Vera A.1; Szarek, Michael2; Aylward, Philip E.3; |
| Organizations: |
1Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama 2State University of New York, Downstate School of Public Health, Brooklyn, New York 3South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, South Australia, Australia
4Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
5Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina 6Sanofi, Bridgewater, New Jersey 7Division of Medicine, Department of Vascular Medicine, Preventive Cardiology Unit, University Medical Centre Ljubljana, Ljubljana, Slovenia 8Medical Faculty, University of Ljubljana, Ljubljana, Slovenia 9Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada 10St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada 11Department of Cardiology, Oslo University Hospital, Oslo, Norway 12University of Oslo, Oslo, Norway 13Sanofi, Paris, France 14Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California 15Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands 16Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, Kansas 17Regeneron Pharmaceuticals Inc., Tarrytown, New York 18Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina 19Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 20Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium 21University of Leuven, Leuven, Belgium 22Division of Cardiovascular Medicine, University of California San Diego, La Jolla, California 23Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado 24Green Lane Cardiovascular Services Auckland City Hospital, Auckland, New Zealand 25Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel 26Department of Medicine III, Goethe University, Frankfurt am Main, Germany 27Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université de Paris, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France 28National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom 29University Hospital of Oulu |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 0.6 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2021102151986 |
| Language: | English |
| Published: |
Elsevier,
2020
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| Publish Date: | 2021-10-22 |
| Description: |
AbstractBackground: 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) see all
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| Series: |
Journal of the American College of Cardiology |
| ISSN: | 0735-1097 |
| ISSN-E: | 1558-3597 |
| ISSN-L: | 0735-1097 |
| Volume: | 75 |
| Issue: | 2 |
| Pages: | 133 - 144 |
| DOI: | 10.1016/j.jacc.2019.10.057 |
| OADOI: | https://oadoi.org/10.1016/j.jacc.2019.10.057 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3121 General medicine, internal medicine and other clinical medicine |
| Subjects: | |
| Funding: |
Sophie Rushton-Smith, Ph.D. (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique - Hôpitaux de Paris, Paris, France. |
| Copyright information: |
© 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |