Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of RiskBut Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

ABSTRACT

Background-—We evaluated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA2 inhibitor, in relation to outcomes and the effects ofdarapladib in the STABILITY trial. Methods and Results-—Plasma Lp-PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100)at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA2activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 lmol/min per liter (interquartile range 143.1–204.2lmol/min per liter). Comparing the highest and lowest Lp-PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) forthe primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) forhospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction afteradjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladibled to a 65% persistent reduction in median Lp-PLA2 activity. There were no associations between on-treatment Lp-PLA2 activityor changes of Lp-PLA2 activity and outcomes, and there were no significant interactions between baseline and on-treatment LpPLA2 activity or changes in Lp-PLA2 activity levels and the effects of darapladib on outcomes...