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
Authors: Wallentin Lars , Held Claes , Armstrong Paul W. , Cannon Christopher P. , Davies Richard Y. , Granger Christopher B. , Hagström Emil , Harrington Robert A. , Hochman Judith S. , Koenig Wolfgang , Krug‐Gourley Sue , Mohler Emile R. , Siegbahn Agneta , Tarka Elizabeth , Steg Philippe Gabriel , Stewart Ralph A. H. , Weiss Robert , Östlund Ollie , White Harvey D. ,   the STABILITY Investigators, Budaj Andrzej , Ardissino Diego , Avezum Alvaro , Aylward Philip E. , Bryce Alfonso , Chen Hong , Chen Ming‐Fong , Corbalan Ramon , Dalby Anthony J. , Danchin Nicolas , De Winter Robbert J. , Denchev Stefan , Diaz Rafael , Elisaf Moses , Flather Marcus D. , Goudev Assen R. , Grinfeld Liliana , Husted Steen , Kim Hyo‐Soo , Linhart Ales , Lonn Eva , López‐Sendón José , Manolis Athanasios J. , Nicolau José C. , Pais Prem , Parkhomenko Alexander , Pedersen Terje R. , Pella Daniel , Ramos‐Corrales Marco A. , Ruda Mikhail , Sereg Mátyás , Siddique Saulat , Sinnaeve Peter , Sritara Piyamitr , Swart Henk P. , Sy Rody G. , Teramoto Tamio , Tse Hung‐Fat , Weaver W. Douglas , Viigimaa Margus , Vinereanu Dragos , Zhu Junren 
Published: June 2016

Background

We evaluated lipoprotein‐associated phospholipase A
2
(Lp‐
PLA
2
) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐
PLA
2
inhibitor, in relation to outcomes and the effects of darapladib in the
STABILITY
trial.

Methods and Results

Plasma Lp‐
PLA
2
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‐
PLA
2
activity levels and outcomes. At baseline, the median Lp‐
PLA
2
level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐
PLA
2
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‐
PLA
2
activity. There were no associations between on‐treatment Lp‐
PLA
2
activity or changes of Lp‐
PLA
2
activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐
PLA
2
activity or changes in Lp‐
PLA
2
activity levels and the effects of darapladib on outcomes.

Conclusions

Although high Lp‐
PLA
2
activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐
PLA
2
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‐
PLA
2
activity.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
00799903.