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Lipoprotein-Associated Phospholipase A(2) Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease JOURNAL OF THE AMERICAN HEART ASSOCIATION Wallentin, L., Held, C., Armstrong, P. W., Cannon, C. P., Davies, R. Y., Granger, C. B., Hagstrom, E., Harrington, R. A., Hochman, J. S., Koenig, W., Krug-Gourley, S., Mohler, E. R., Siegbahn, A., Tarka, E., Steg, P. G., Stewart, R. A., Weiss, R., Ostlund, O., White, H. D. 2016; 5 (6)

Abstract

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 of darapladib in the STABILITY trial.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-PLA2 activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 µmol/min per liter (interquartile range 143.1-204.2 µmol/min per liter). Comparing the highest and lowest Lp-PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23-1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29-2.93) for hospitalization for heart failure, 1.42 (1.07-1.89) for cardiovascular death, and 1.37 (1.03-1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ˜65% persistent reduction in median Lp-PLA2 activity. There were no associations between on-treatment Lp-PLA2 activity or changes of Lp-PLA2 activity and outcomes, and there were no significant interactions between baseline and on-treatment Lp-PLA2 activity or changes in Lp-PLA2 activity levels and the effects of darapladib on outcomes.Although high Lp-PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp-PLA2 activity by ˜65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp-PLA2 activity.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

View details for DOI 10.1161/JAHA.116.003407

View details for Web of Science ID 000386712700045

View details for PubMedID 27329448

View details for PubMedCentralID PMC4937279