1 research outputs found
LipoproteinâAssociated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease
Background: We evaluated lipoproteinâassociated phospholipase A2 (LpâPLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective LpâPLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma LpâPLA2 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 LpâPLA2 activity levels and outcomes. At baseline, the median LpâPLA2 level was 172.4 ÎŒmol/min per liter (interquartile range 143.1â204.2 ÎŒmol/min per liter). Comparing the highest and lowest LpâPLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23â1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29â2.93) for hospitalization for heart failure, 1.42 (1.07â1.89) for cardiovascular death, and 1.37 (1.03â1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a â65% persistent reduction in median LpâPLA2 activity. There were no associations between onâtreatment LpâPLA2 activity or changes of LpâPLA2 activity and outcomes, and there were no significant interactions between baseline and onâtreatment LpâPLA2 activity or changes in LpâPLA2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high LpâPLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of LpâPLA2 activity by â65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of LpâPLA2 activity