Author + information
- Received March 14, 2018
- Revision received April 23, 2018
- Accepted April 25, 2018
- Published online July 9, 2018.
- Robert S. Rosenson, MDa,∗ (, )
- Robert A. Hegele, MDb,
- Sergio Fazio, MD, PhDc and
- Christopher P. Cannon, MDd
- aZena and Michael A. Wiener Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, New York
- bDepartment of Medicine and Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada
- cOregon Health & Science University, Knight Cardiovascular Institute, Center for Preventive Cardiology, Portland, Oregon
- dCardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Robert S. Rosenson, Cardiometabolics Unit, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Hospital Box 1030, New York, New York 10029.
Variants in proprotein convertase subtilisin/kexin type 9 (PCSK9) provide insights into mechanisms regulating low-density lipoprotein (LDL) levels. Human monoclonal antibodies that target PCSK9 lower LDL cholesterol (LDL-C) levels by 55% to 72% in different high-risk patient groups. Clinical trials with PCSK9 inhibitors have demonstrated reductions in atherosclerotic cardiovascular disease events, particularly in patients with recent acute coronary syndrome, multivessel coronary artery disease, or peripheral arterial disease. Commonly observed profound reductions in LDL-C to levels <25 mg/dl have been accompanied by even lower rates of atherosclerotic cardiovascular disease events, thus supporting the concept that there may be no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been accompanied by a safety profile that has been very favorable. On the basis of clinical trial evidence, LDL lowering with PCSK9 inhibitors is recommended for high-risk patients with LDL-C levels ≥70 mg/dl on maximally tolerated oral therapies including statins and/or ezetimibe.
- acute coronary syndrome
- atherosclerotic cardiovascular disease
- coronary artery disease
- low-density lipoprotein
- peripheral arterial disease
Dr. Rosenson has received research grants through his institution from Akcea, Amgen, AstraZeneca, Medicines Company, and Regeneron; has served on advisory boards for Akcea, Amgen, C5, CVS Caremark, Regeneron, and Sanofi; has received honoraria from Akcea, Kowa, and Pfizer; has received royalties from UpToDate; and has stock ownership in MediMergent. Dr. Hegele has received consulting fees from Aegerion, Acasti, Akcea/Ionis, Amgen, Sanofi, and Pfizer. Dr. Fazio has received consulting fees from Aegerion, Amarin, Amgen, Kowa, and Akcea. Dr. Cannon has received research grants from Amgen, Arisaph, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, Merck, and Takeda; and consulting fees from Alnylam, Amarin, Amgen, Arisaph, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Kowa, Lipimedix, Merck, Pfizer, Regeneron, Sanofi, and Takeda. John J.P. Kastelein, MD, PhD, served as Guest Editor for this paper.
- Received March 14, 2018.
- Revision received April 23, 2018.
- Accepted April 25, 2018.
- 2018 American College of Cardiology Foundation
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