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Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod.

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Date
2015
Authors
Kragholm, Kristian
Newby, Laura Kristin
Melloni, Chiara
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Abstract
Each year, despite optimal use of recommended acute and secondary prevention therapies, 4%-5% of patients with acute coronary syndrome (ACS) experience relapse of ACS or other cardiovascular events including stroke, heart failure, or sudden cardiac death after the index ACS. The sudden atherosclerotic plaque rupture leading to an ACS event is often accompanied by inflammation, which is thought to be a key pathogenic pathway to these excess cardiovascular events. Losmapimod is a novel, oral p38 mitogen-activated protein kinase (MAPK) inhibitor that targets MAPKs activated in macrophages, myocardium, and endothelial cells that occur as a part of global coronary vascular inflammation following plaque rupture. This review aims to 1) discuss the pathophysiological pathways through which p38 MAPKs may play key roles in initiation and progression of inflammatory disease and how losmapimod is thought to counteract these p38 MAPKs, and 2) to describe the efficacy and safety data for losmapimod obtained from preclinical studies and randomized controlled trials that support the hypothesis that it has promise as a treatment for patients with ACS.
Type
Journal article
Subject
efficacy
losmapimod
outcomes
p38 MAPK
p38 MAPK inhibitor
safety
Acute Coronary Syndrome
Animals
Anti-Inflammatory Agents
Cardiovascular Agents
Cyclopropanes
Enzyme Activation
Humans
Membrane Proteins
Protein Kinase Inhibitors
Pyridines
Signal Transduction
Treatment Outcome
Permalink
https://hdl.handle.net/10161/12504
Published Version (Please cite this version)
10.2147/DDDT.S69546
Publication Info
Kragholm, Kristian; Newby, Laura Kristin; & Melloni, Chiara (2015). Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod. Drug Des Devel Ther, 9. pp. 4279-4286. 10.2147/DDDT.S69546. Retrieved from https://hdl.handle.net/10161/12504.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Melloni

Chiara Melloni

Adjunct Associate Professor in the Department of Medicine
Newby

Laura Kristin Newby

Professor of Medicine
Research Description General Focus: Clinical investigation the process and treatment of acute and chronic coronary artery disease and systems issues for delivery of care to patients with these illnesses. Particular interests include management of patients with chest pain and unstable angina, evaluation of the use of biochemical markers other than CK-MB for diagnosis and risk stratification in these patients, issues related to coronary artery disease in women, and systems issues
Alphabetical list of authors with Scholars@Duke profiles.
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