1887
Volume 2015, Issue 1
  • ISSN: 2305-7823
  • EISSN:

Abstract

Lipoprotein associated phospholipase A2 (Lp-PLA) - an enzyme with several pro-inflammatory properties - has been hypothesized to be involved in the pathogenesis of atherosclerosis and plaque vulnerability. Lp-PLA activity has been demonstrated to be an independent predictor of coronary heart disease (CHD) and ischemic stroke. However, it has been recently reported that carriers of loss of function variants in PLA2G7 gene (encoding Lp-PLA2) had no lower CHD risk than non-carriers. The (STABILITY), and the (SOLID-TIMI 52) studies are two phase III, randomized, placebo-controlled, clinical trials that were conducted to evaluate the clinical efficacy and safety of the Lp-PLA2 inhibitor (darapladib), against a background of optimal medical therapy, in patients with stable CHD and acute coronary syndrome, respectively. In both studies, darapladib failed to reduce the risk of major coronary events as compared to placebo. In addition, darapladib was associated with significantly higher rates of drug discontinuation, and adverse side effects such as diahrrea and malodorous feces, urine, and skin, as compared to placebo. These data suggest that Lp-PLA may be a biomarker of vascular inflammation rather than a causal pathway of cardiovascular (CV) diseases. It also challenges the notion that inhibition of Lp-PLA is a worthwhile approach in patients with CHD. Alternate therapies that target inflammation are awaited to reduce residual risk in patients with CV diseases.

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2015-03-01
2020-11-26
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