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Darapladib: an emerging therapy for atherosclerosis.
MedLine Citation:
PMID:  20660537     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Despite a reduction in cardiovascular risk conferred by therapies that modify circulating lipids, a need remains for novel treatments to further decrease the occurrence of complications of atherosclerotic cardiovascular diseases. Lipoprotein-associated phospholipase-A(2) is an important regulator of lipid metabolism and inflammation that circulates with lipoprotein particles and is carried into the arterial wall with low-density lipoprotein particles during the progression of atherosclerosis. Within the vessel wall, lipoprotein-associated phospholipase-A(2) releases small molecules that stimulate macrophage recruitment and evolution to foam cells, leading to plaque vulnerability. Epidemiologic studies demonstrate that elevated circulating levels of lipoprotein-associated phospholipase-A(2) predict an increased risk of myocardial infarction and stroke, whereas histologic examination of diseased human coronary arteries reveals intense presence of the enzyme in atherosclerotic plaques that are prone to rupture. These considerations suggest lipoprotein-associated phospholipase-A(2) as a promising therapeutic target, and a specific inhibitor, darapladib, has been under development for this application. This review summarizes the completed preclinical and early phase clinical studies that underlie two recently commenced phase III clinical trials that will investigate the efficacy and safety of darapladib in nearly 13,000 individuals with coronary heart disease. When completed, these trials should provide important insights into the utility of darapladib to reduce myocardial infarction, stroke and cardiovascular death.
Authors:
Marshall A Corson
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Publication Detail:
Type:  Journal Article     Date:  2010-07-26
Journal Detail:
Title:  Therapeutic advances in cardiovascular disease     Volume:  4     ISSN:  1753-9455     ISO Abbreviation:  Ther Adv Cardiovasc Dis     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2011-02-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101316343     Medline TA:  Ther Adv Cardiovasc Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  241-8     Citation Subset:  IM    
Affiliation:
Divisions of Cardiology and Cardiovascular Research, University of Washington School of Medicine, Harborview Medical Center, Room 2EH-64, 325 9th Avenue, Seattle, WA 98104, USA. mcorson@u.washington.edu.
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