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JAMA. 2014 Sep 10;312(10):1006-15. doi: 10.1001/jama.2014.11061.

Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial.

Collaborators (1086)

Braunwald E, Cannon CP, Bode C, Hochman J, Maggioni AP, Steg P, Serruys P, Weaver D, White HD, Lukas MA, Davies RY, Braunwald E, Cannon CP, O'Donoghue ML, Steen DP, Crugnale SE, Lamp JM, McCourt A, Barakat D, Mezzetti J, Morrison C, Stevens M, Ward C, Ardissino D, Aylward PE, Babilonia N, Britto F, Budaj A, Cannon CP, Chen SA, Corbalán R, Dalby AJ, Dellborg M, deWinter RJ, Dorobantu M, Duris T, Gao R, Goudev AR, Grande P, Gratsiansky N, Guneri S, Hamm C, Husted S, Isaza D, Kimura T, Kiss R, Lewis B, López-Sendón J, Mancini GB, Mathur A, Mittal S, Montalescot G, Nicolau JC, Ophuis TO, Paolasso E, Parkhomenko A, Ray K, Reddy K, Seung KB, Somaraju B, Spinar J, Sritara P, Theroux P, White HD, Wijns W, Collins R, Anderson J, DeMets D, Ganz P, Sandercock P, Weber M, Fisher M, Buhr K, Diegel S, Schultz M, Wiviott SD, Lowe C, Mills K, Ruvido J, Alkhalil M, Rehman MQ, Stebletsova I, Shimmer M, Forni D, Awtry E, Berger CJ, Croce K, Desai A, Gelfand E, Ho C, Leeman DE, Link MS, Pande A, Ruberg F, Vita JA, Gignac G, Hochberg E, Lane A, Rosenberg C, Wagner A, Wolpin BM, Goessling W, Bonaca MP, Acquilano DE, Waltemyer R, Kunder S, Syed A, Aigbogun J, Taylor M, Daga S, Cicconetti G, Davies RY, Nandy I, Shannon J, Deenadayalu N, Im K, Koduru S, Murphy S, Zhou J, Abraham L, Beloscar J, Bettinotti M, Dumont C, Fernandez R, Fuentealba VJ, Covelli G, García Durán R, Hominal MA, Jure H, Litvak M, Luciardi H, Macin S, MacKinnon I, Milesi R, Montaña O, Olavegogeascoechea P, Prado A, Sala J, Gorosito V, Sassone S, Maffei L, Schmuck R, Vico M, Vita N, Arstall M, Ashby D, Colquhoun D, Cross D, Farshid A, Freeman M, New G, Hammett C, Kanna R, Lehman R, Roberts-Thomson P, William M, Yamen E, Beauloye C, Beunk J, Boland J, Charlier F, Claeys M, Dujardin K, Friart A, Legrand V, Schoors D, Sinnaeve P, Vandenbossche JL, Abrantes J, Alves da Costa F, Ardito W, Bodanese L, Braga JC, Carvalho A, Dutra O, Feitosa G, Guimarães AE, Hernandes M, Leães P, Lima F, Lotufo P, Maia L, Manenti E, Mattos MA, Michalaros Y, Paiva MS, Piegas L, Pimentel Filho P, Precoma D, Rabelo Alves Junior Á, Rassi S, Reis G, Resende E, Rossi P, Saraiva JF, Silva Júnior D, Silva FA, Souza J, Wainstein M, Ribeiro J, Benov H, Chompalova B, Goshev E, Raev D, Goudev A, Grigorov M, Grigorova V, Mihov A, Nikolov F, Petrov I, Postadzhiyan A, Ramshev K, Tisheva S, Tzekova M, Bhargava R, Cha J, Constance C, Davies R, Della Siega A, Klinke P, Dong R, Dupuis R, Gyenes G, Huynh T, Labonte R, Lai C, Leader R, Leiter L, Lonn E, Nguyen M, Pandey A, Polasek P, Ramanathan K, Rose B, Rupka D, Sabbah E, Syan G, Tishler S, Vizel S, Zeman P, Albornoz Alarcon FJ, Castro Galvez P, Florenzano Urzua F, Pedemonte Villablanca OA, Pérez Pino L, Pincetti C, Rodriguez Venegas M, Romero Castro C, Lamich R, Sepulveda Varela PA, Stockins B, Chen Y, Dong Y, Fu G, Gao R, Hao Y, Huang D, Jiao Y, Ke Y, Li C, Li H, Li T, Li X, Li Z, Liao D, Liu L, Lu Q, Qu P, Shen Z, Shi H, Wu S, Xiang M, Xu J, Chen Y, Yang X, Yu J, Yuan Z, Zhang Y, Zhou S, Accini Mendoza JL, Bohorquez R, Botero R, Cano Lopez N, Hernandez H, Isaza D, Jaramillo C, Jaramillo M, Jaramillo N, Manzur F, Mendoza F, Reynales H, Sanchez Vallejo G, Ternera A, Urina M, Cermak O, Coufal Z, Dedek V, Francek L, Grunfeldova H, Gregor P, Grunfeldova H, Kellnerova I, Klimsa Z, Kuchar L, Linhart A, Mayer O, Spinar J, Taborsky M, Vitovec J, Andersen U, Kristensen K, Bang L, Grande P, Brønnum-Schou J, Egstrup K, Frost L, Galatius S, Husted S, Jeppesen J, Rokkedal J, Klarlund K, Laursen R, Nielsen T, Melchior T, Mickley H, Nielsen H, Nielsen W, Schmidt E, Sjøl A, Skagen K, Sykulski R, Zeuthen E, Nyvad O, Agraou B, Bayet G, Caussin C, Coisne D, Cottin Y, Decoulx E, Delahaye F, Delarche N, D'Houdain F, Dourmap-Collas C, Dubois-Rande JL, Elbaz M, Cottin Y, Decoulx E, Martelet M, Montalescot G, Nallet O, Cattan S, Ohlmann P, Schiele F, Steg G, Traisnel G, Tricot O, Berrouschot J, Duengen HD, Elsaesser A, Erbel R, Moehlenkamp S, Franz N, Frey N, Hambrecht R, Hamm C, Haude M, Janssens U, Joost A, Schunkert H, Kadel C, Katus H, Koenig W, Laufs U, Loew A, Klauss V, Koenig A, Sohn HY, Mudra H, Neumann FJ, Olbrich HG, Plehn A, Buerke M, Ebelt H, Schaefer A, Fischer D, Schaeufele T, Steiner S, Kreuzer J, Tsoy I, Stellbrink C, Sydow K, Baldus S, Tiroch K, Guelker H, Haltern G, Voehringer HF, Weber D, Werner G, Zeiher AM, Zeymer U, Zirlik A, Csapó K, Herczeg B, Katona A, Keltai K, Kiss RG, László Z, Lupkovics G, Medvegy M, Merkely B, Müller G, Nagy A, Nagy L, Pálinkás A, Sziliczei-Németh, Sereg M, Valcó J, Vértes A, Zámolyi K, Arora P, Bali H, Banker D, Chaganti VR, Chandra PK, Chopra A, Christopher J, Dani S, Gupta S, Shah S, Hiremath S, Kaul U, Koduganti S, Kumar N, Kumar S, Mandala G, Mathur A, Naik S, Oomman A, Padmanabhan TN, Parikh K, Reddy RP, Roy S, Sankardas M, Sapra R, Chopra V, Sathe S, Sawhney J, Atar S, Banai S, Eldar M, Elis A, Gavish D, Goldhaber A, Gottlieb S, Hayek T, Hussein O, Katz A, Klutstein M, Kracoff O, Lewis B, Lishner M, Lotan C, Meisel S, Mosseri M, Qarawani D, Hasin Y, Rozenman Y, Schiff E, Oliven A, Weiss A, Ardissino D, Baldin MG, Berni A, Biasucci LM, Bongo A, Campo G, Valgimigli M, Colivicchi F, De Servi S, Esposito G, Gavazzi A, Marzilli M, Merlini P, Moretti L, Morocutti G, Mos L, Patrizi G, Rapezzi C, Branzi A, Terrosu P, Domae H, Fujii S, Furukawa Y, Goto Y, Hirokami M, Ito H, Kawajiri K, Kimura K, Kimura T, Kuramochi T, Miyauchi K, Muroya T, Hata S, Yoshida T, Oku K, Okutsu M, Ooie T, Saito T, Shimomura H, Shinozaki N, Shishido K, Sugitatsu K, Tanaka S, Suwa S, Takenaka T, Tamada A, Tanabe K, Tanaka Y, Takahashi S, Yamazaki S, Chae SC, Hong TJ, Jeong JO, Jeong M, Kim HS, Kim YH, Ko YG, Lee SH, Seung KB, Yoon J, Bartels L, Basart D, De Nooijer C, Dijkgraaf R, de Graaf JJ, Groutars R, Visser J, Hamer BJ, Hamraoui K, Heijmeriks J, Huizenga A, Herrman JP, Knufman NM, Frederiks J, Kuijper AF, Lenderink T, van der Meer P, Milhous GJ, Nierop P, Oude Ophuis AJ, Peerenboom P, Peters R, Plomp J, Prins P, Schaap A, van der Sluis A, Smeele FJ, van Hal JM, Swart HP, Tjeerdsma G, Troquay R, Van Eck M, Viergever E, de Weerd GJ, van Daele M, de Winter RJ, Zoet-Nugteren SK, van der Zwaan C, Zwart P, Devlin G, Elliott J, Harrison N, Hart H, O'Meeghan T, Stewart R, Ternouth I, Tisch J, van Pelt N, Wilkins G, Chen V, Alarco Leon W, Rodriguez Chávez VE, Rojas Cañamero R, Rotta Rotta A, Toce L, Añonuevo J, Babilonia N, Barcinas R, Coching RM, Matiga G, Sulit DJ, Uy N, Bronisz M, Budaj A, Buszman P, Dalkowski M, Derlaga B, Fijalkowski M, Rynkiewicz A, Firek B, Gil R, Jaworska K, Kasprzak J, Krzeminska-Pakula M, Kleinrok A, Kopaczewski J, Kuc K, Kusnierz B, Lewczuk J, Lysek R, Miekus P, Mirek-Bryniarska E, Mlodziankowski A, Musial W, Mysiak A, Napora P, Piepiorka M, Pluta W, Prochaczek F, Przewlocki T, Rekosz J, Rusicka T, Galaj A, Sciborski R, Szelemej R, Szpajer M, Wojewoda P, Wrzosek B, Zurakowski A, Arsenescu Georgescu CM, Benedek I, Capalneanu R, Cinteza M, Craiu E, Cristea M, Dimulescu D, Dorobantu M, Fruntelata AG, Ginghina C, Minescu B, Musetescu R, Ionescu D, Pop C, Radoi M, Sinescu C, Vinereanu D, Arkhipov M, Barbarash O, Bessonova N, Boldueva S, Boyarkin M, Demko A, Duplyakov D, Ermoshkina L, Glezer M, Goloshchekin B, Gordeev I, Gratsiansky N, Grinshtein Y, Karpov Y, Kobalava Z, Konstantinov V, Kostenko V, Kuimov A, Kuznetsov V, Libis R, Markov V, Motylev I, Novikova N, Orlikova O, Panchenko E, Panov A, Ruda M, Sementsov D, Shalaev S, Shvarts Y, Simanenkov V, Skorichenko V, Sukmanova I, Smolenskaya O, Tsyba L, Vishnevsky A, Yakhontov D, Yakusevich V, Zadionchenko V, Zateyshchikov D, Zateyshchikova A, Zrazhevskiy K, Duris T, Fridrich V, Gaspar L, Hasilla J, Hranai M, Kokles M, Pella D, Basson M, Bayat J, Blignaut S, Burgess L, Corbett C, Da Silva A, Dalby A, De Jong D, Mabin T, Manga P, Oosthuysen W, Ranjith N, Roodt A, Roux J, Soma P, Swanepoel N, Theron H, van Zyl L, Barrabes Riu JA, Figueras Bellot J, Bayón Fernández J, Simarro Martin-Ambrosio E, Benedicto Buendía A, Castro Conde A, Íñiguez Romo A, Jiménez Navarro M, López García-Aranda V, Mainar Tello V, Marco Garde P, Mayordomo López J, Mollá Jimenez C, Antón Pascual JL, Mollá Jimenez C, Plaza Pérez I, Ridocci Soriano F, Viles Beltrán D, Bandh S, Christensen K, Dellborg M, Herlitz J, Karlsson JE, Mooe T, Persson B, Timberg I, Witt N, Chen SA, Cheng CC, Hung HH, Lai WT, Tu CM, Li AH, Wu CF, Wu CJ, Yin WH, Buakhamsri A, Kaewsuwanna P, Kiatchoosakun S, Kuanprasert S, Sritara P, Wongpraparut N, Bayata S, Guneri S, Yavuzgil O, Amosova E, Batushkin V, Dyadyk O, Goloborodko B, Karpenko O, Kononenko L, Kopytsya M, Koval O, Kovalskyy I, Legkonogov O, Malynovsky Y, Shershnyova O, Netiazhenko V, Nikonov V, Parkhomenko O, Prokhorov O, Rebrov B, Potapenko P, Rudenko L, Shcherbak V, Stanislavchuk M, Tseluyko V, Yagensky A, Ahsan A, Been M, Bethell H, Senior R, Cox D, Findlay I, Fisher M, Gandhi M, Gorog D, Jacques A, Keeling P, O'Rourke B, Pell A, Spratt J, Trouton T, Wong YK, Abadier R, Abrahams L, Afonso L, Aggarwal A, Aggarwal K, Ahmed A, Ahmed S, Albirini A, Anderson J, Angiolillo D, Ansari S, Applegate R, Arif I, Leesar M, Aronow H, Asbill B, Ashraf R, Atalay H, Atassi K, Atieh M, Babayan Z, Harjai K, Baker S, Barr L, Barringhaus K, Bayron C, Benjamin S, Benton R, Berglund R, Conn E, Bertolet B, Bhagwat R, Biederman R, Bisher E, Blanchard A, Brown C, Butman S, Campbell C, Canaday D, Carlson T, Casale P, Cashion W Jr, Chandler A, Chandna H, Chandrasekaran S, Chang G, Chronos N, Chang M, Chhabra A, Chin J, Cochran D, Cohen K, Cucher F, Dauber I, De Gregorio M, Del Core M, Dewhurst R, Rodriguez R, Dionisopoulos P, Donovan D, Doty W, Drossner M, East C, Eaton G, Ebrahimi R, Effron B, Elkhadra M, Elsner G, Erickson B, Fehrenbacher G, Feldman R, Fernandes V, Fishberg R, Flores A, Foreman R, Frankel R, French W, Fuentes F, Fujise K, Fulmer J, Gabry M, Baig M, Curran P, Garcia Pulido J, Gatien L, Gazmuri R, Gencheff N, Gilmore R, Giugliano G, Goldberg R, Goldman S, Movahed MR, Goldstein M, Gonzalez D, Gottlieb D, Grabarczyk M, Graham B, Gruberg L, Gumm D, Gupta S, Lee D, Hage-Korban E, Hakas J, Hamroff G, Harris B, Hearne S, Held J, Henderson DA, Hermany P, Herzog W, Hinchman D, Fry S, Hockstad E, Hodson R, Hollenbaugh D, Horwitz P, Hurst P, Ibrahim H, Imburgia M, Izzo M, Jaffrani N, Jan M, Janout M, Ring M, Jones S, Kahn B, Kakavas P, Kates A, Bach R, Katopodis J, Kazimir M, Kennett J, Kereiakes D, Kersh R, Kershner D, Meilman H, Kerwin P, Khera A, Kieval J, Kim E, Kobayashi J, Nelson R, Kosinski E, Kovacich D, Kraft P, Kramer J, Kruse K, Kuvin J, Labib A, Labroo A, Langer M, Lau T, Lee K, Movahed MR, Lee T, Levite H, Lewis D, Lieber I, Loh I, Lopez M, Lui H, Malkowski M, Mammen G, Mascolo R, Matsumura M, Matthews G, Corbelli J, Mayer T, McAlhany C, McCullum K, Meholick A, Mehta V, Melhado M, Menees D, Miller M, Minisi A, Minor S, Moore C, Nygaard T, Morcos N, Morris P, Morrow D, Mostel E, Murdock D, Nadar V, Nahhas A, Navas J, Nukta E, Oberoi M, O'Donnell P, Ostfeld R, Pacheco T, Panchal V, Parang P, Paraschos A, Pasquini J, Williams J Jr, Patlola R, Peart B, Penny W, Pepine C, Perlman R, Pavlides A, Popeil L, Prashad R, Price D, Price R, Puleo P, Puri S, Raikhel M, Ramachandran A, Ramos M, Concha M, Randhawa P, Reichek N, Riba A, Ricciardi M, Rider J, Fenton S, Rizvi MA, Dahiya R, Rogers W, Roth D, Rowe W, Saba F, Sabri M, Patel P, Sandoval J, Sangrigoli R, Schwartzbard A, Seidner M, Shah A, Shanes J, Sharma M, Siegel C, Singal D, Singh N, Smith A, Panetta C, Smith S, Whitaker J, Snell J, Snyder H, Soffer A, Sonel A, Spencer R, Staniloae C, Stephenson C, Sundaram S, Sutton L, Letts D, Swint R Sr, Tallet J, Tami L, Taylor R, Hanovich G, Tedder B, Teufel E, Brett C, Thomas J, Thompson P, Polk D, Tilkian A, Tinkel J, Pandya U, Tobiansky J, Trippi J, Tuohy E, Uretsky B, Uusinarkaus K, Varma S, Velasquez E, Vogel C, Voyce S, Wainwright W, Hancock H, Walder J, Wali A, Watkins S, Weiss R, Wickemeyer W, Wilson D, Wilson V, Wiseman A, Wright W Jr, Xenakis M, Zelenka J, Zilz N, Amidon T.

Erratum in

  • JAMA. 2014 Oct 8;312(14):1473. Dylan P. Steen[corrected to Dylan L. Steen].

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-PLA2 enzyme.

OBJECTIVE:

To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event.

DESIGN, SETTING, AND PARTICIPANTS:

SOLID-TIMI 52 was 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-elevation myocardial infarction [MI]) at 868 sites in 36 countries.

INTERVENTIONS:

Patients were randomized to either once-daily darapladib (160 mg) 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 for myocardial 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-PLA2 with 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.

PMID:
25173516
DOI:
10.1001/jama.2014.11061
[PubMed - indexed for MEDLINE]
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