Therapeutic Options to Reduce Lp-PLA2 Levels and the Potential Impact on Vascular Risk Reduction

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Opinion statement

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in the metabolism of Low-density lipoprotein (LDL) to pro-inflammatory mediators. Lp-PLA2 is highly expressed in the necrotic core of atherosclerotic plaques and has been associated with atherosclerotic plaque instability. Multiple studies have shown an association between elevated Lp-PLA2 levels and risk of both stroke and myocardial infarction, even after adjustment for standard vascular risk factors, and several professional organizations have recommended Lp-PLA2 as a potentially usefully tool to improve risk stratification for individual patients. Therapies directed at lowering Lp-PLA2 levels may represent a novel approach to reducing vascular risk, though direct clinical benefit from targeting treatment to Lp-PLA2 levels remains unproven. Statins appear to significantly lower Lp-PLA2 levels; fibrates and niacin may also lower Lp-PLA2 levels, though this is less well established. Darapladib, a potent, selective Lp-PLA2 inhibitor, is currently in phase III trials for prevention of recurrent vascular events in patients with coronary artery disease.