Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease

Harvey White, Claes Held, Ralph Stewart, Elizabeth Tarka, Rebekkah Brown, Richard Davies, Andrzej Budaj, Robert Harrington, Philippe Steg, Diego Ardissino, Paul Armstrong, Alvaro Avezum, Philip Aylward, Alfonso Bryce, Hong Chen, Ming-Fong Chen, Ramon Corbalan, Anthony Dalby, Nicolas Danchin, Robbert De WinterStefan Denchev, Rafael Diaz, Moses Elisaf, Marcus Flather, Assen Goudev, Christopher Granger, Liliana Grinfeld, Judith Hochman, Steen Husted, Hyo-Soo Kim, Wolfgang Koenig, Ales Linhart, Eva Lonn, Jose López-Sendón, Athanasios Manolis, Emile Mohler III, José Nicolau, Prem Pais, Alexander Parkhomenko, Terje Pedersen, Daniel Pella, Marco Ramos-Corrales, Mikhail Ruda, Mátyás Sereg, Saulat Siddique, Peter Sinnaeve, Peter Smith, Piyamitr Sritara, Henk Swart, Rody Sy, Tamio Teramoto, Hung-Fat Tse, David Watson, W Weaver, Robert Weiss, Margus Viigimaa, Dragos Vinereanu, Junren Zhu, Christopher Cannon, Lars Wallentin

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    334 Citations (Scopus)

    Abstract

    BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P = 0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P = 0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P = 0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke.

    Original languageEnglish
    Pages (from-to)1702-1711
    Number of pages10
    JournalNew England Journal of Medicine
    Volume370
    Issue number18
    DOIs
    Publication statusPublished - 2014

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  • Cite this

    White, H., Held, C., Stewart, R., Tarka, E., Brown, R., Davies, R., Budaj, A., Harrington, R., Steg, P., Ardissino, D., Armstrong, P., Avezum, A., Aylward, P., Bryce, A., Chen, H., Chen, M-F., Corbalan, R., Dalby, A., Danchin, N., ... Wallentin, L. (2014). Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease. New England Journal of Medicine, 370(18), 1702-1711. https://doi.org/10.1056/NEJMoa1315878