Genetic invalidation of Lp-PLA as a therapeutic target: Large-scale study of five functional Lp-PLA-lowering alleles.

Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A (Lp-PLA), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA enzyme activity is causally relevant to coronary heart disease. Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.