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N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.

Ticagrelor versus clopidogrel in patients with acute coronary syndromes.

Collaborators (1118)

Wallentin L, James S, Ekman I, Emanuelsson H, Freij A, Thorsen M, Harrington RA, Becker R, Cannon C, Horrow J, Husted S, Katus H, Skene A, Storey RF, Steg PG, Ardissino D, Aylward P, Babilonia N, Bassand JP, Budaj A, Chapichadze Z, Claeys MJ, Commerford P, Cornel JH, Verheugt F, Duris T, Gao R, Armando GC, Giannitsis E, Gurbel P, Harrington R, Kleiman N, Sabatine M, Weaver D, Heras M, Husted S, James S, Keltai M, Kontny F, Kremastinos D, Lassila R, Lewis BS, Sendon JL, Yu CM, Maurer G, Meier B, Morais J, Nicolau J, Parkhomenko AN, Oto A, Pais P, Paolasso E, Raev D, Zambahari DS, Ruda M, Santoso A, Seung KB, Teik LS, Spinar J, Sritara P, Storey R, Théroux P, Vintila M, Wu DW, Anderson JL, DeMets D, Simoons M, Wilcox R, Van de Werf F, Harrington RA, Wallentin L, Becker R, Cannon C, Husted S, James S, Katus H, Skene A, Steg PG, Storey R, Emanuelsson H, Freij A, Horrow J, Thorsén M, Becker R, Ekman I, Emanuelsson H, Fitt S, Freij A, Giordani M, Harrington RA, Horrow J, James S, Khurmi N, Thorsén M, Wallentin L, Ardissino D, Aylward P, Babilonia N, Bassand JP, Budaj A, Chapichadze Z, Claeys MJ, Commerford P, Cornel JH, Duris T, Gao R, García Castillo A, Giannitsis E, Gurbel P, Harrington R, Heras M, Husted S, James S, Keltai M, Kleiman N, Kontny F, Kremastinos D, Lassila R, Lewis BS, Sendon JL, Yu CM, Maurer G, Meier B, Morais J, Nicolau J, Parkhomenko AN, Oto A, Pais P, Paolasso E, Raev D, Zambahari DS, Ruda M, Sabatine M, Santoso A, Seung KB, Teik LS, Spinar J, Sritara P, Storey R, Théroux P, Weaver D, Verheugt F, Vintila M, Wu DW, Anderson JL, DeMets D, Simoons M, Wilcox R, Van de Werf F, Anderson S, Iverson E, Mahaffey KW, Held C, Dickerson S, Högberg M, Montgomery D, Healy J, Khurmi N, Paniflov S, Senk F, Vanaman L, Alexander J, Al-Khatib S, Berger J, Bushnell C, Chew D, Cohen M, Craig J, De Lemos J, French J, Giugliano R, Goodman S, Greenbaum A, Hernandez A, Katz J, Lopes R, Madan M, Mahaffey K, McCullough P, McGuire D, Mehta R, Melloni C, Morrow D, Newby K, Roe M, Russell S, Scirica B, Shah B, Szczech L, Whellan D, Wiviott D, Bennermo M, Christersson C, Eggers K, Fredlund BO, Götberg M, Hagström E, Held C, Hijazi Z, Holmgren M, James S, Jernberg T, Johnston N, Jönelid B, Koul S, Lundman P, Oldgren J, Nilehn KS, Samuelsson O, Szummer K, Varenhorst C, Akerblom A, Cairns R, Skene A, Pieper K, Olofsson S, Ycas J, Becker R, Harrington RA, Ekman I, James S, Wallentin L, Schygiel P, Allall O, Ramos H, Bono J, Fuselli J, Cuneo C, Colombo H, Navarro Estrada J, Pasinato C, Nul D, Berli M, Milesi R, Hominal M, Fernandez R, Hrabar A, Luciardi H, Muntaner J, Zapata G, Macin S, Bettinoti M, Bluguermann JJ, Hasbani EG, Piraino R, Colombo Berra F, Garcia Escudero A, Vaile J, Walters D, Dart T, Hii C, Garrahy P, Amerena J, Counsell J, Arnolda L, Maurer G, Huber K, Roithinger F, Hofer J, Brussee H, Krappinger H, Nesser J, Siostrzonek P, Pachinger O, Drexel H, Cools F, Eycken M, Goldstein M, Lancellotti P, Mathieu F, Materne P, Raymenants E, Van Mieghem W, Claeys M, Benit E, Dubois P, El Allaf D, Heynickx G, Striekwold H, Timmermans P, Lima F, Piegas L, Lotufo P, Golin V, Carvalho A, Maia L, Greque G, Saraiva JF, Filho P, Dutra O, Ribeiro J, Leaes P, Manenti E, Abrantes JA, Rossi PR, Filho H, Albuquerque D, Reis G, Rabelo A, Teixeira M, Júnior D, Garcia MF, Oliveira LA, Paiva MS, Michalaros Y, Batista Júnior J, Júnior R, Dohmann HF, Rassi S, Sousa AC, Gomes M, Maia E, Neto J, Botelho R, Raev D, Goudev A, Marchev S, Mihov A, Popov A, Cekova M, Dimitrova S, Denchev S, Grigorov M, Tisheva S, Penev A, Hazarbasanov D, Petranov S, Petranov S, Boichev B, Shehova N, Hergeldjieva V, Vladimirov T, Nikolov F, Djurdjev A, Theroux P, Swan J, Rose B, Constance C, Ramanathan K, Klinke WP, Cantor W, Welsh R, Ducas J, Polasek P, Thanh TH, Bhargava R, Teskey R, Vizel S, Deyoung JP, Comtois H, Ma P, Dupuis R, Heath J, Dion D, Cleveland D, Rupka D, Radhakrishnan S, Brockville JB, Zimmermann R, Nguyen M, Cabau JR, Le May M, Kostuk W, Kornder J, Chen J, Yang X, Lv S, Huo Y, Zhu J, Li Z, Huang D, Chen J, He B, Hua Q, Han Y, Spinar J, Holub M, Mandysova E, Belohlavek J, Reichert P, Cermak O, Dedek V, Cervinka P, Horak D, Holm F, Groch L, Motovska Z, Spacek R, Matejka J, Pleva L, Stipal R, Richter M, Povolny J, Vojacek J, Vejvoda J, Coufal Z, Monhart Z, Christensen PD, Sørensen E, Dodt K, Frost L, Dalsgaard D, Markenvard J, Nyvad O, Pedersen K, Sykulski R, Klarlund K, Dahlstrøm C, Melchior T, Jakobsen T, Jensen J, Skagen K, Rasmussen S, Nielsen JE, Brønnum-Schou J, Grande P, Tuxen C, Nielsen T, Petersen J, Roseva-Nielsen N, Mcnair A, Olsen ME, Nielsen H, Tierala I, Ylitalo A, Utriainen S, Hartikainen J, Airaksinen J, Voutilainen S, Nyman K, Halkosaari M, Hadjikov A, Bassand JP, Poulard JE, El Mansour N, Leroy F, Traisnel G, Decoulx E, Maes D, Lamit X, Maupas E, Bayet G, Gacem K, Cassat C, Coste P, Delarche N, Ledain L, Mougeot G, Hannebicque G, Rihani R, Philippe F, Blanc JJ, Farah B, Le Breton H, Koning R, Henry P, Escande M, Dubois-Rande JL, Elhadad S, Grollier G, Cottin Y, Garot P, Dibon O, Rousseau JF, Labeque JN, Ohlmann P, Khanoyan P, Chumburidze V, Paposhvili K, Megreladze I, Kobulia B, Emukhvari N, Melia A, Mamatsashvili M, Chapidze G, Khabeishvili G, Giannitsis E, Darius H, Dahl J, Franz N, Strasser RH, Borst M, Kuck KH, Gülker H, Lüders S, Genth-Zotz S, Heuer H, Buerke M, Jeron A, Hengstenberg C, Felix S, Nienaber C, Konstantinides S, Schöls W, Lins M, Simon R, Schunkert H, Brachmann J, Dorsel T, Niroomand F, Horacek T, Kreuzer J, Grönefeld G, Leschke M, Dannberg G, Yazar A, Mitrovic V, Stumpf J, Koenig W, Prondzinsky R, Stangl V, Rauch U, Kirchhof P, Wassmann S, Werner N, Kadel C, Uebis R, Monti J, Gastmann O, Lapp H, Klues HG, Bühler A, Schaaf DU, Fischer D, Grosch B, Schäfer A, Vöhringer HF, Dissmann M, Kremastinos D, Foussas S, Manolis A, Vardas P, Theodorakis G, Voudris V, Triposkiadis F, Alexopoulos D, Parharidis G, Ju CM, Czigány A, Edes I, Horváth I, Jánosi A, Kalina A, Katona A, Piróth Z, Király C, Lupkovics G, Sereg M, Oze B, Kássa L, Takács J, Merkely B, Mágel F, Pálinkás A, Vértes A, Pais P, Byrapaneni RB, Pothineni RB, Banker D, Chandra P, Chandwani P, Kottaram H, Premchand RK, Jain S, Mardikar H, Mohanan P, Chandrakasu A, Nayar P, Omar A, Panwar R, Parikh K, Paul SK, Pinto R, Saligrama RS, Sawhney JP, Trivedi S, Varma S, Bhuvaneswaran S, Santoso A, Soerianata S, Erwinanto E, Rifqi S, Suryawan IG, Finkelstein A, Kracoff O, Gottlieb S, Hasin Y, Zahger D, Lewis B, Lotan C, Bloch L, Rosenschein U, Rozenman Y, Meisel S, Klutstein M, Katz A, Vered Z, Perna G, De Luca I, Gavazzi A, Tamburino C, Ferrari R, Zuppiroli A, Antoniucci D, Di Biase, De Servi S, Zanini R, Raviele A, Presbitero P, Klugmann S, Modena M, Pio C, Sante Bongo A, Azienda LV, Bramucci E, Paloscia L, Vassanelli C, Boccanelli A, Giovannini E, Volpe M, Fanelli R, Terrosu P, Olivari Z, Uriarte JS, Fedele F, Mascia F, Auguadro C, Specchia G, Ammirati F, Berti S, Zambahari R, Sim K, Ismail O, Ahmad WA, García A, Benavides M, Ramos G, Cardona E, Gutierrez Fajardo P, Romo A, Martinez C, Meaney A, Meaney A, Velasco R, Nuñez JC, Perez J, Cornel JH, Verheugt F, Alings M, Bendermacher P, Van den Berg B, Beyerbacht H, Michels R, Dijkgraaf R, Van der Linde M, Groutars R, Hamer B, Den Hartog F, Van der Heijden R, Holwerda K, Janssen M, Nicastia D, Jap-Tjoen-San W, Aengevaeren W, Gho B, De Leeuw M, Liem A, Kruik H, Lok D, Ophuis AO, Peters R, Pieterse M, Plomp J, Ten Berg J, Van Rossum P, De Medina RR, Smits P, Dirkali A, Thijssen H, Viergever E, Withagen A, Van der Zwaan C, Van Boven A, Waltenberger J, Erdal LE, Rolstad O, Hurtig U, Andersen K, Høgalmen G, Jørgensen B, Heggelund G, Fanebust R, Eivindson G, Gundersen T, Omland T, Lappegård KT, Gjertsen E, Smith P, Berget K, Atar D, Lid N, Gullestad L, Babilonia N, Anonuevo J, To R, Rogelio G, Molleno E, Estalilla C 3rd, Coching RM, Budaj A, Buszman P, Dalkowski M, Gil R, Kleinrok A, Krasowski W, Lewczuk J, Pluta W, Szelemej R, Szwed H, Gessek J, Miekus P, Kubica J, Reszka Z, Krzciuk M, Kusnierz B, Piepiorka M, Dabrowski M, Górny J, Kardaszewicz P, Rekosz J, Ruminski W, Rynkiewicz A, Sciborski R, Buszman P, Targonski R, Wrzosek B, Wysocki H, Derlaga B, Goch JH, Jaworska K, Kopaczewski J, Sinkiewicz W, Tracz W, Dudek D, Drzewiecki A, Hoffmann A, Nizankowski R, Kornacewicz-Jach Z, Kurowski M, Mazurek W, Musial W, Bronisz M, Szpajer M, Stopinski M, Morais J, Arroja I, Diogo N, Santos JF, Marques L, Proença G, Da Silva G, Gonçalo L, Mendes S, Gonçalves C, Cardoso P, Moreira I, Pereira LM, Vintila M, Cinteza M, Georgescu CA, Capalneanu R, Radoi M, Ionescu D, Stanciulescu G, Minescu B, Spiridon M, Creteanu M, Constantinescu M, Duda A, Lesnyak O, Arkhipov M, Ovcharenko E, Akhunova S, Dembitskaya A, Barbarash O, Pavlov P, Ustyugov S, Nechepurenko G, Linev K, Shulman V, Gordeev I, Ruda M, Zateyshchikov D, Sidorenko B, Klein G, Fomin I, Kosmachova E, Belenky D, Ganyukov V, Baum S, Khaisheva L, Katelnitskaya L, Miftyakhova R, Burova N, Boldueva S, Sherbak A, Petrov A, Kostenko V, Filippov A, Vishnevsky A, Markov V, Kuznetsov V, Verin V, Lim ST, Nair D, Lim IH, Lim J, Duris T, Fridrich V, Vahala P, Cuncik P, Belicova M, Studencan M, Remisova S, Kycina P, Macek V, Spisak V, Urban M, Hranai M, Brice E, Weich H, Badenhorst J, Horak A, Dawood S, Theron H, Mabin T, Seung KB, Chae IH, Cho YS, Lee CW, Tahk SJ, Yoon JH, Jang YS, Jeong MH, Kim YJ, Roque Moreno M, García Picart J, De Teresa Galván E, Macaya Miguel C, Iñiguez Romo A, Rey Blas JR, Ruano Marco M, Figueras Bellot J, Bethencourt González A, López García V, Valentín Segura V, Batalla Celorio LA, Vigil-Escalera González P, Worner Diz F, Jara Clemente F, Marcos Gómez G, James S, Bandh S, Samnegård A, Cherfan P, Nilsson C, Karlsson JE, Peterson M, Mooe T, Hårdhammar P, Zedigh C, Lycksell M, Rydén S, Janzon M, Jovinge S, Kallryd A, Pripp CM, Tygesen H, Stjärna A, Meier B, Moccetti T, Pieper M, Roffi M, Vérin V, Pagnamenta A, Gallino A, Brack M, Baur HR, Wen MS, Chen WJ, Chen YH, Hou C, Chen MC, Sritar P, Srimahachota S, Kuanprasert S, Wongvipaporn C, Sansanayudh N, Oto A, Ertas F, Temizhan A, Yigit Z, Demir M, Cin G, Belgi A, Yaymaci B, Krayz I, Kononenko L, Tseluyko V, Parkhomenko A, Karpenko O, Koval O, Rudenko L, Vatutin M, Kalinkina N, Storey R, Lip G, More R, Khattar R, Hudson I, Squire I, De Belder M, Pell A, Oldroyd K, Lang C, Fox K, Herity N, Moriarty A, Ramsey M, O'Callaghan P, Wilkins M, Bruce D, Bishop A, Lanza S, Lau T, Henderson D, Walker J, Imburgia M, Gurbel P, Raffeto J, Donovan J, Nadar V, Minor S, Rogers W, Lester F, Bengston J, Leimbach W, Singh V, Rivera E, Vicari R, Anderson J, Papademetriou V, Rich M, Purdy D, Casale P, Corbelli J, Guidera S, Murphy J, Wu W, Gordon J, Kar B, Lingham D, Davidenko J, Friedman B, Lim M, Ghali M, Sinden J, Silver M, Lui H, Yakubov S, Weiss R, Virmani A, Matthai W, Shamoon F, Ebrahimi R, Fattal P, Kraus D, Sarma R, Feldman R, Mulumudi M, Tolerico P, Patterson J, Voyles W, Gupta K, Hearne S, Schneider D, Atassi K, Bikkina M, Doorey A, Fernandes V, Gordon P, Langevin G, Mckay R, Mehta V, Aycock G, Angiolillo D, Reicher B, Schwartz B, Kini A, Sharma S, Yasin M, Fields R, Popma J, Shah PB, Staniloae C, Carlson T, Verlee P, Culp S, Leesar M, Ikram S, Shaikh S, Mclellan B, Panetta C, Raveenderan G, Dave R, Lieberman S, Jain A, Beto R, Gelormini J, Anderson HV, Banks A, Chandna H, Chandrashekhar Y, Cheek HB, Del Core M, French W, Harris J, Jinich D, Kent K, Khan M, Kraft P, Lassar T, Sacchi T, Kozman H, Prashad R, San G, Villa A, Drenning D, Applegat R, Hermany P, Karlsberg R, Degregorio M, Bach R, Giugliano G, Graham B, Bowden W, Rosenberg M, Patel P, Brilakis E, Fenton S, Gassler J, Johnson J Jr, Mclaurin B, Sonel A, Chhabra A, Vossenberg F, Horwitz P, Baran K, Lader E, Magee A, Chambers J, Delemos J, Addo T, Fehrenbacher G, Grossman P, Harjai K, Jamal N, Albirini A, Atanasoski-Mccormack V, Ayres T, Aggarwal K, Chang D, Labroo A, Wilson V, Rodriguez-Ospina L, Whitney R, Lopez J, Nathan S, Schaer G, Weinstock B, Xenopoulos N, Zidar F, Blankenship J, Hirsch C, Williams M, Mcgrew F, Ranadive N, Reen B, Iwaoka R, Iwaoka R, Skowronski J, Lamas G, Rice K, Yalamanchili V, Touchon R, Wasserman H, Kaluski E, Lowry R, Mathew T, Karia D, Rabah M, Movahed MR, Ricciardi M, Foster M, Eisenberg D, Fischell T, Brechtken J, Shetty S, Trippi J, Rossi J, Cohen M, Cohn J, Fintel D, Tami L, O'Leary E, Safley D, Stuckey T, Aggarwal A.

Abstract

BACKGROUND:

Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel.

METHODS:

In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation.

RESULTS:

At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types.

CONCLUSIONS:

In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872.)

2009 Massachusetts Medical Society

PMID:
19717846
[PubMed - indexed for MEDLINE]
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