Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Jun 2016)
Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease
- Lars Wallentin,
- Claes Held,
- Paul W. Armstrong,
- Christopher P. Cannon,
- Richard Y. Davies,
- Christopher B. Granger,
- Emil Hagström,
- Robert A. Harrington,
- Judith S. Hochman,
- Wolfgang Koenig,
- Sue Krug‐Gourley,
- Emile R. Mohler,
- Agneta Siegbahn,
- Elizabeth Tarka,
- Philippe Gabriel Steg,
- Ralph A. H. Stewart,
- Robert Weiss,
- Ollie Östlund,
- Harvey D. White,
- Andrzej Budaj,
- Diego Ardissino,
- Alvaro Avezum,
- Philip E. Aylward,
- Alfonso Bryce,
- Hong Chen,
- Ming‐Fong Chen,
- Ramon Corbalan,
- Anthony J. Dalby,
- Nicolas Danchin,
- Robbert J. De Winter,
- Stefan Denchev,
- Rafael Diaz,
- Moses Elisaf,
- Marcus D. Flather,
- Assen R. Goudev,
- Liliana Grinfeld,
- Steen Husted,
- Hyo‐Soo Kim,
- Ales Linhart,
- Eva Lonn,
- José López‐Sendón,
- Athanasios J. Manolis,
- José C. Nicolau,
- Prem Pais,
- Alexander Parkhomenko,
- Terje R. Pedersen,
- Daniel Pella,
- Marco A. Ramos‐Corrales,
- Mikhail Ruda,
- Mátyás Sereg,
- Saulat Siddique,
- Peter Sinnaeve,
- Piyamitr Sritara,
- Henk P. Swart,
- Rody G. Sy,
- Tamio Teramoto,
- Hung‐Fat Tse,
- W. Douglas Weaver,
- Margus Viigimaa,
- Dragos Vinereanu,
- Junren Zhu
Affiliations
- Lars Wallentin
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Claes Held
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Paul W. Armstrong
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada
- Christopher P. Cannon
- Cardiovascular Division, Brigham and Women's Hospital, Boston, MA
- Richard Y. Davies
- Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA
- Christopher B. Granger
- Medical Center, Duke University, Durham, NC
- Emil Hagström
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Robert A. Harrington
- Department of Medicine, Stanford University, Stanford, CA
- Judith S. Hochman
- Department of Medicine, NYU Langone Medical Center, New York, NY
- Wolfgang Koenig
- Department of Internal Medicine II‐Cardiology, University of Ulm Medical Center, Ulm, Germany
- Sue Krug‐Gourley
- Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA
- Emile R. Mohler
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Agneta Siegbahn
- Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden
- Elizabeth Tarka
- Former Employee of Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, King of Prussia, PA
- Philippe Gabriel Steg
- FACT (French Alliance for Cardiovascular Trials), Paris, France
- Ralph A. H. Stewart
- Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand
- Robert Weiss
- Maine Research Associates, Auburn, ME
- Ollie Östlund
- Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden
- Harvey D. White
- Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand
- Andrzej Budaj
- Diego Ardissino
- Alvaro Avezum
- Philip E. Aylward
- Alfonso Bryce
- Hong Chen
- Ming‐Fong Chen
- Ramon Corbalan
- Anthony J. Dalby
- Nicolas Danchin
- Robbert J. De Winter
- Stefan Denchev
- Rafael Diaz
- Moses Elisaf
- Marcus D. Flather
- Assen R. Goudev
- Liliana Grinfeld
- Steen Husted
- Hyo‐Soo Kim
- Ales Linhart
- Eva Lonn
- José López‐Sendón
- Athanasios J. Manolis
- José C. Nicolau
- Prem Pais
- Alexander Parkhomenko
- Terje R. Pedersen
- Daniel Pella
- Marco A. Ramos‐Corrales
- Mikhail Ruda
- Mátyás Sereg
- Saulat Siddique
- Peter Sinnaeve
- Piyamitr Sritara
- Henk P. Swart
- Rody G. Sy
- Tamio Teramoto
- Hung‐Fat Tse
- W. Douglas Weaver
- Margus Viigimaa
- Dragos Vinereanu
- Junren Zhu
- DOI
- https://doi.org/10.1161/JAHA.116.003407
- Journal volume & issue
-
Vol. 5,
no. 6
Abstract
BackgroundWe 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 ResultsPlasma 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. ConclusionsAlthough 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. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.
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