Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a unique member of the phospholipase fami ly. In the blood it travels mainly with low-density lipoproteins (LDL). Less than 20% is associated with high-density lipoproteins. It is an enzyme produced by inflammatory cells and hydrolyzes oxidized phospholipids in LDL. Clinical studies have reported that plasma Lp-PLA2 activity and mass are strongly associated with atherogenic lipids and vascular risk. Lp-PLA2 is involved in the development of atherosclerosis. A meta-analysis involving a total of 79’036 participants in 32 prospective studies found that Lp-PLA2 levels are positively correlated with increased risk of developing coronary heart disease and stroke. These observations led to the hypothesis that Lp-PLA2 activity and/or mass levels could be used as biomarkers of cardiovascular disease and that inhibition of the activity could offer an attractive therapeutic strategy. Darapladib, a compound that inhibits Lp-PLA2 activity, was the first drug of this class that was tested. Dose-dependent inhibition of Lp-PLA2 by darapladib was found, ranging from 43% to 66% compared with placebo control group. The inf lammatory markers interleukin-6 and high-sensitivity C-reactive protein were also reduced. There are 2 phase III studies underway on these agents. STABILITY trial is a randomized, doubleblind placebo-control led trial of darapladib for with chronic coronary patients. The trial has enrolled over 15500 patients from 800 clinical centres worldwide and report on the primary outcome of major adverse cardiovascular events. SOLIDTMI 52 trial has enrolled approximately 11500 participants within 30 days of acute myocardial infarction (MI). Participants have been randomized to darapladib or placebo and followed for 3 years for the outcomes of cardiovascular death, nonfatal MI, or stroke. These studies will determine whether Lp-PLA2 inhibition with darapladib is associated with favourable effects on cardiovascular events.