Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod.
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 articleSubject
efficacylosmapimod
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
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https://hdl.handle.net/10161/12504Published Version (Please cite this version)
10.2147/DDDT.S69546Publication 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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Show full item recordScholars@Duke
Chiara Melloni
Adjunct Associate Professor in the Department of Medicine
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
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