Vera A. Bittner, Michael Szarek, Philip E. Aylward, Deepak L. Bhatt, Rafael Diaz, Jay M. Edelberg, Zlatko Fras, Shaun G. Goodman, Sigrun Halvorsen, Corinne Hanotin, Robert A. Harrington, J. Wouter Jukema, Virginie Loizeau, Patrick M. Moriarty, Angèle Moryusef, Robert Pordy, Matthew T. Roe, Peter Sinnaeve, Sotirios Tsimikas, Robert Vogel, Harvey D. White, Doron Zahger, Andreas M. Zeiher, Ph. Gabriel Steg, Gregory G. Schwartz, Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome, Journal of the American College of Cardiology, Volume 75, Issue 2, 2020, Pages 133-144, ISSN 0735-1097, https://doi.org/10.1016/j.jacc.2019.10.057.
Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome
|Author:||Bittner, Vera A.1; Szarek, Michael2; Aylward, Philip E.3;|
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
|Online Access:||PDF Full Text (PDF, 0.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021102151986
|Publish Date:|| 2021-10-22
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)
Journal of the American College of Cardiology
|Pages:||133 - 144|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
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.
© 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/).