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J Am Coll Cardiol. 2018 Jul 17;72(3):314-329. doi: 10.1016/j.jacc.2018.04.054. Epub 2018 Jul 9.

The Evolving Future of PCSK9 Inhibitors.

Author information

1
Zena 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. Electronic address: robert.rosenson@mssm.edu.
2
Department of Medicine and Robarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada.
3
Oregon Health & Science University, Knight Cardiovascular Institute, Center for Preventive Cardiology, Portland, Oregon.
4
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Abstract

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.

KEYWORDS:

acute coronary syndrome; atherosclerotic cardiovascular disease; coronary artery disease; low-density lipoprotein; peripheral arterial disease

PMID:
30012326
DOI:
10.1016/j.jacc.2018.04.054

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