Abstract
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor as strong as low-density lipoprotein (LDL) cholesterol. Therapies targeting Lp-PLA2 in plasma and plaque are now being developed. This article will review these data. Lp-PLA2 is intimately involved in the development of atherosclerosis and is found in vulnerable human plaques. Multiple epidemiological studies have shown that Lp-PLA2 is related to the occurrence of myocardial infarction (MI), stroke and vascular death.Darapladib is a novel oral compound that selectively inhibits Lp-PLA2 in plasma and in human plaques. Darapladib has also been shown to halt necrotic core progression in coronary arteries over a 12-month period and to have few adverse effects. Two large phase III trials are randomizing 26,000 patients to darapladib or placebo with chronic coronary heart disease or following an acute coronary syndrome. The primary composite outcomes are cardiovascular death, MI or stroke and results should be available in 2012. Darapladib has the potential to improve patient outcomes in addition to evidence-based treatments by modulating mechanisms of disease that have not been addressed by current therapies.
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