@article{6429767ff1d84e88ac712c0a0f149662,
title = "Effect of darapladib on major coronary events after an acute coronary syndrome: The SOLID-TIMI 52 randomized clinical trial",
abstract = "IMPORTANCE: Lipoprotein-associated phospholipase A2(Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2enzyme. OBJECTIVE: To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event. DESIGN, SETTING, AND PARTICIPANTS: SOLID-TIMI 52was a multinational, double-blind, placebo-controlled trial that randomized 13 026 participants within 30 days of hospitalization with an ACS (non-ST-elevation or ST-elevationmyocardial infarction [MI]) at 868 sites in 36 countries. INTERVENTIONS: Patients were randomized to either once-daily darapladib (160mg) or placebo on a background of guideline-recommended therapy. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. MAIN OUTCOMES AND MEASURES: The primary end point (major coronary events)was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization formyocardial ischemia. Kaplan-Meier event rates are reported at 3 years. RESULTS: During a median duration of 2.5 years, the primary end point occurred in 903 patients in the darapladib group and 910 in the placebo group (16.3%vs 15.6%at 3 years; hazard ratio [HR], 1.00 [95%CI, 0.91-1.09]; P = .93). The composite of cardiovascular death, MI, or stroke occurred in 824 in the darapladib group and 838 in the placebo group (15.0%vs 15.0%at 3 years; HR, 0.99 [95%CI, 0.90-1.09]; P = .78). There were no differences between the treatment groups for additional secondary end points, for individual components of the primary end point, or in all-cause mortality (371 events in the darapladib group and 395 in the placebo group [7.3%vs 7.1%at 3 years; HR, 0.94 [95%CI, 0.82-1.08]; P = .40). Patients were more likely to report an odor-related concern in the darapladib group vs the placebo group (11.5%vs 2.5%) and also more likely to report diarrhea (10.6%vs 5.6%). CONCLUSIONS AND RELEVANCE: In patients who experienced an ACS event, direct inhibition of Lp-PLA2with darapladib added to optimal medical therapy and initiated within 30 days of hospitalization did not reduce the risk of major coronary events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000727",
keywords = "Darapladib, acute coronary syndrome, atherogenesis, Lipoprotein-associated phospholipase A2 (Lp-PLA2), Lp-PLA2 enzyme",
author = "O'Donoghue, {Michelle L.} and Eugene Braunwald and White, {Harvey D.} and Steen, {Dylan P.} and Lukas, {Mary Ann} and Elizabeth Tarka and Steg, {P. Gabriel} and Hochman, {Judith S.} and Christoph Bode and Maggioni, {Aldo P.} and Im, {Kyung Ah} and Shannon, {Jennifer B.} and Davies, {Richard Y.} and Murphy, {Sabina A.} and Crugnale, {Sharon E.} and Wiviott, {Stephen D.} and Bonaca, {Marc P.} and Watson, {David F} and Weaver, {W. Douglas} and Serruys, {Patrick W.} and Cannon, {Christopher P.} and {SOLID-TIMI 52 Investigators} and Steen, {D. P.} and Lamp, {J. M.} and A. McCourt and D. Barakat and J. Mezzetti and C. Morrison and M. Stevens and C. Ward and D. Ardissino and Aylward, {P. E.} and N. Babilonia and F. Britto and A. Budaj and Chen, {S. A.} and R. Corbal{\'a}n and Dalby, {A. J.} and M. Dellborg and deWinter, {R. J.} and M. Dorobantu and T. Duris and R. Gao and A. Goudev and P. Grande and N. Gratsiansky and S. Guneri and C. Hamm and S. Husted and D. Isaza and T. Kimura and R. Kiss and B. Lewis and J. L{\'o}pez-Send{\'o}n and Mancini, {G. B.} and A. Mathur and S. Mittal and G. Montalescot and Nicolau, {J. C.} and Ophuis, {T. O.} and E. Paolasso and A. Parkhomenko and K. Ray and K. Reddy and Seung, {K. B.} and B. Somaraju and J. Spinar and P. Sritara and P. Theroux and W. Wijns and R. Collins and J. Anderson and D. DeMets and P. Ganz and P. Sandercock and M. Weber and M. Fisher and K. Buhr and S. Diegel and M. Schultz and C. Lowe and K. Mills and J. Ruvido and M. Alkhalil and Rehman, {M. Q.} and I. Stebletsova and M. Shimmer and D. Forni and E. Awtry and Berger, {C. J.} and K. Croce and A. Desai and E. Gelfand and C. Ho and Leeman, {D. E.} and Link, {M. S.} and A. Pande and F. Ruberg and Vita, {J. A.} and G. Gignac and E. Hochberg and A. Lane and C. Rosenberg and A. Wagner and Wolpin, {B. M.} and W. Goessling and Acquilano, {D. E.} and R. Waltemyer and S. Kunder and A. Syed and J. Aigbogun and M. Taylor and S. Daga and G. Cicconetti and I. Nandy and N. Deenadayalu and S. Koduru and J. Zhou and L. Abraham and J. Beloscar and M. Bettinotti and C. Dumont and R. Fernandez and Fuentealba, {V. J.} and G. Covelli and {Garc{\'i}a Dur{\'a}n}, R. and Hominal, {M. A.} and H. Jure and M. Litvak and H. Luciardi and S. Macin and I. MacKinnon and R. Milesi and O. Monta{\~n}a and P. Olavegogeascoechea and A. Prado and J. Sala and V. Gorosito and S. Sassone and L. Maffei and R. Schmuck and M. Vico and N. Vita and M. Arstall and D. Ashby and D. Colquhoun and D. Cross and A. Farshid and M. Freeman and G. New and C. Hammett and R. Kanna and R. Lehman and P. Roberts-Thomson and M. William and E. Yamen and C. Beauloye and J. Beunk and J. Boland and F. Charlier and M. Claeys and K. Dujardin and A. Friart and V. Legrand and D. Schoors and P. Sinnaeve and Vandenbossche, {J. L.} and J. Abrantes and {Alves da Costa}, F. and W. Ardito and L. Bodanese and Braga, {J. C.} and A. Carvalho and O. Dutra and G. Feitosa and Guimar{\~a}es, {A. E.} and M. Hernandes and P. Le{\~a}es and F. Lima and P. Lotufo and L. Maia and E. Manenti and Mattos, {M. A.} and Y. Michalaros and Paiva, {M. S.} and L. Piegas and {Pimentel Filho}, P. and D. Precoma and {Rabelo Alves Junior}, A. and R. Labonte and M. Nguyen and Y. Chen and X. Li and H. Li and H. Li and X. Li and Z. Li and S. Wu and J. Yu and Y. Zhang and L. Frost and T. Nielsen and D. Weber and S. Roy and S. Gupta and R. Sapra and T. Yoshida and Hong, {T. J.} and Kim, {H. S.} and Lee, {S. H.} and J. Elliott and N. Harrison and R. Stewart and V. Kuznetsov and Yin, {W. H.} and D. Cox and Wong, {Y. K.} and A. Ahmed and S. Ahmed and J. Anderson and S. Baker and C. Brown and C. Campbell and J. Chin and R. Foreman and D. Lee and B. Harris and Henderson, {D. A.} and H. Ibrahim and S. Jones and K. Lee and T. Lee and D. Lewis and M. Miller and C. Moore and P. Morris and J. Williams and R. Price and A. Ramachandran and M. Ramos and W. Rogers and A. Smith and S. Smith and R. Spencer and L. Sutton and R. Taylor and C. Brett and J. Thomas and P. Thompson and D. Wilson and A. Wiseman",
year = "2014",
month = sep,
day = "10",
doi = "10.1001/jama.2014.11061",
language = "English",
volume = "312",
pages = "1006--1015",
journal = "JAMA: Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Assocation",
number = "10",
}