Targeting the unstable plaque in acute coronary syndromes.
BACKGROUND
Rupture or erosion of an unstable atherosclerotic plaque is the typical pathology and usual cause of acute coronary syndromes. Despite detailed understanding of the processes of lipid accumulation, thinning of the fibrous cap, and inflammation leading to plaque instability, there are no strategies in clinical use that uniquely target the unstable plaque.


OBJECTIVE
A critical review of recent publications on potential therapies that could be used to stabilize unstable plaque.


METHODS
We searched PubMed, other literature databases, drug development sites, and clinical trial registries to retrieve clinical studies on anti-inflammatory and lipid-modulating therapies that could be used to stabilize unstable atherosclerotic plaque.


RESULTS
Multiple experimental targets involving lipid and inflammatory pathways have the potential to stabilize the plaque and expand the armamentarium against coronary artery disease. Randomized clinical trials of darapladib, methotrexate, canakinumab, and colchicine are well advanced to establish if plaque stabilization is feasible and effective in patients with acute coronary syndromes.


CONCLUSIONS
Although there are still no agents in clinical use for plaque stabilization, there are important advances in understanding plaque instability and several encouraging approaches are being evaluated in Phase III clinical trials.
['Thompson|Peter L|PL|', 'Nidorf|S Mark|SM|', 'Eikelboom|John|J|']
D054058:Acute Coronary Syndrome D000818:Animals D000893:Anti-Inflammatory Agents D002784:Cholesterol D008078:Cholesterol, LDL D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D062645:Percutaneous Coronary Intervention D064801:Phospholipase A2 Inhibitors D058226:Plaque, Atherosclerotic
acute coronary syndromes plaque instability darapladib methotrexate canakinumab colchicines atherosclerosis