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 of darapladib 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-PLA2 activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 lmol/min per liter (interquartile range 143.1-204.2 lmol/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. Conclusions--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. © 2016 The Authors.
Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease / Wallentin, L., Held, C., Armstrong, P.w., Cannon, C.p., Davies, R.y., Granger, C.b., Hagström, E., Harrington, R.a., Hochman, J.s., Koenig, W., Krug-Gourley, S., Mohler ER, 3., Siegbahn, A., Tarka, E., Steg, P.g., Stewart, R.a., Weiss, R., Östlund, O., White, H.d., Ardissino, D., et al.. - In: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE. - ISSN 2047-9980. - 5:(2016). [10.1161/JAHA.116.003407]
Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease
Ardissino D;
2016-01-01
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 of darapladib 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-PLA2 activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 lmol/min per liter (interquartile range 143.1-204.2 lmol/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. Conclusions--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. © 2016 The Authors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
