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N Engl J Med. 2016 Jul 7;375(1):35-43. doi: 10.1056/NEJMoa1603060. Epub 2016 May 10.

Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

Collaborators (745)

Easton J, Ameriso SF, Donnan G, Lemmens R, Massaro A, Titianova E, Hill MD, Lavados P, Wang Y, Skoloudik D, Amarenco P, Röther J, Wong KS, Norbert S, Agnelli G, Bornstein N, Tanahashi N, Góngora AA, Pretell E, San Jose MC, Czlonkowska A, Bajenaru O, Stakhovskaya L, Brozman M, Kim JS, Molina CA, Wahlgren N, Michel P, Lee TH, Suwanwela NC, Kutluk K, Moskovko S, Kasner S, Laskowitz D, Clark W, Nguyen HT, Ameriso SF, Ameriso S, Lepera S, Romano M, Paulon D, Ioli P, Zurru C, Bruera G, Jure L, Klein F, Povedano G, Donnan G, Levi C, Phan T, Markus R, Anderson C, Sabet A, Davis S, Lee A, Kleinig T, Wong A, Krause M, Jannes J, Wijeratne T, Lemmens R, Lemmens R, Hemelsoet D, Peeters A, Tack P, Vanacker P, Laloux P, Van Landegem W, Vanhooren G, Desfontaines P, Van Orshoven M, Massaro A, Oliveira F, Friedrich M, Brondani R, Gagliardi R, Fabio S, Dracoulakis M, Bazan R, Marrone L, Pontes Neto O, Silva G, Kowacs P, Titianova E, Titianova E, Stamenova P, Daskalov M, Staikov I, Baldaranov D, Maslarov D, Lilovski H, Petkov P, Petrova N, Mavrov R, Markova V, Petrova V, Beleva T, Kralev B, Sotirov N, Lekova V, Hristov D, Ermenkova V, Mateev L, Mitkova R, Haralanov L, Ikonomov R, Mihailova M, Georgiev I, Hill MD, Shuaib A, Hachinski V, Boulanger JM, Mann S, Hassan A, Mackey A, Menon B, Minuk J, Siddiqui M, Eustace M, Vieira L, Selchen D, Beaudry M, Stotts G, Lavados P, Lavados P, Castro A, Gasic K, Rivas R, Sanchez P, Roldan A, Grossmann I, Figueroa C, Wang Y, Wang Y, Li J, Xu X, Chen H, Li X, Yang Y, Zhang C, Wang B, Li G, Wang D, Lin H, Tang Y, Xu A, Wang Y, Hong W, Song Z, Zhang X, Jin X, Xu Y, Yan F, Zheng W, Wang X, Dong Q, Zhao Z, Zhang B, Zhong W, Wen G, Xu J, Li G, Dong X, Tian X, Zhang Z, Xu E, Liu K, Chen J, Skoloudik D, Skoda O, Skoloudik D, Ehler E, Vaclavik D, Sanak D, Klimosova S, Vitkova E, Fiksa J, Mikulik R, Neumann J, Plny R, Amarenco P, Amarenco P, Leys D, Sibon I, Mas JL, Alamowitch S, Pico F, Hosseini H, Mahagne MH, Touze E, Vadot W, Vannier S, Nighoghossian N, Samson Y, Garnier P, Ellie E, Guillon B, Timsit S, Giroud M, Philippeau F, Bagan-Triquenot A, Wolff V, Raposo N, Obadia M, Debiais S, Grimaud J, Illouz S, Smadja D, Urbanczyk C, Röther J, Röther J, Berrouschot J, Weimar C, Gahn G, Soda H, Klimpe S, Nabavi D, Glahn J, Köhrmann M, Krause L, Terborg C, Urban P, Steiner T, Ferbert A, Dziewas R, Seidel G, Thomalla G, Wong KS, Wong KS, Li R, Fong WC, Cheung R, Szegedi N, Szegedi N, Pozsegovits K, Valikovics A, Pánczél G, Rózsa C, Németh L, Diószeghy P, Óváry C, Csányi A, Kerényi L, Nagy V, Komoly S, Bereczki D, Molnár S, Kondákor I, Bornstein N, Tanne D, Raphaeli G, Telman G, Bornstein N, Leker R, Lampl Y, Agnelli G, Agnelli G, Corea F, Ricci S, Guidetti D, Malferrari G, Marcheselli S, Micieli G, Zini A, Di Lazzaro V, Gandolfo C, Salmaggi A, Tassi R, Rasura M, Orlandi G, Comi G, Ricci S, Mancuso M, Delodovici M, Bovi P, Consoli D, Tanahashi N, Utsugisawa K, Fujita T, Kurihara H, Maruki C, Hayashi T, Ogiichi T, Kumagai M, Takenaka K, Toyoda K, Takamatsu K, Ogami R, Kin S, Aoki T, Takizawa K, Omori S, Umezawa T, Toba Y, Nonoyama Y, Nakagawa H, Naka T, Morimoto M, Matsumoto S, Hitotsumatsu T, Shingaki T, Okuda S, Ota M, Sakai N, Yamada T, Niwa J, Fujita H, Moriki A, Yoshino K, Fukushima Y, Mori T, Sato A, Kusano Y, Kubo M, Yamazaki M, Ooasa T, Nishizaki T, Kitagawa N, Yasaka M, Manabe Y, Yoshioka A, Ishihara M, Kagawa T, Ichihashi T, Matsuoka H, Ito Y, Yamasaki M, Takaba H, Saito H, Sato M, Fukuda K, Endo S, Kidooka M, Umemura T, Kikkawa Y, Toru S, Yamada K, Sakai H, Asari J, Ezura M, Nitta H, Nagano K, Ochiai J, Sakai K, Kobayashi Y, Yoshii Y, Miake H, Takita T, Taniguchi H, Kuroki K, Mizota T, Yamamoto K, Nakane H, Iwanaga T, Chiba K, Yoshimoto T, Torii T, Kitagawa T, Takashima H, Shirasaki N, Dehara M, Wada N, Hamada K, Kato N, Go Y, Izumi I, Ninomiya H, Kumai J, Nakajima Y, Kaku Y, Isayama Y, Kawanishi M, Noda S, Yamamoto K, Hazama T, Takahashi H, Tanaka Y, Hata T, Kazekawa K, Furui E, Hondo H, Sato N, Kusunoki K, Nanri K, Abe S, Sasaoka N, Kuroyanagi T, Suzuki H, Fukuyama K, Nakahara K, Góngora AA, Gongora F, Góngora AA, Brito CC, Careaga JV, Alfaro RV, Leytte GA, Pretell E, Berrospi P, Chavez C, Pretell E, Rodriguez L, Custodio N, Castañeda C, Perez J, Marquez SV, San Jose MC, San Jose MC, Baroque A, Collantes ME, Aquino A, Díaz A, Roxas A Jr, Lokin J, Advincula J, Calderon E, Navarro J, Hiyadan J, Surdilla A, Czlonkowska A, Czlonkowska A, Ryglewicz D, Krychowiak G, Fryze W, Sobolewski P, Nowak R, Fiszer U, Papierowska B, Zielińska-Turek J, Lasek-Bal A, Kołodziejska E, Kamińska A, Adamkiewicz B, Tutaj A, Szkopek D, Musiatowicz K, Bąk Z, Brzozowski S, Brola W, Ferens A, Zalisz M, Rejdak K, Rudzińska M, Bajenaru O, Bajenaru O, Panea C, Simu M, Balasa R, Cuciureanu I, Popescu B, Sabau M, Roman-Filip C, Stakhovskaya L, Pimenov L, Gekht A, Milto A, Shchukin I, Parfenov V, Stakhovskaya L, Arkhipov M, Vishneva E, Sokolova N, Bogdanov E, Esin R, Khasanova D, Golikov K, Melnikova E, Zaslavskiy L, Voznyuk I, Nazarov A, Akhmadeeva L, Iakupova A, Shamalov N, Belskaya G, Chuprina S, Denisova O, Drozdova E, Karakulova Y, Sholomov I, Spirin N, Vostrikova E, Mordvintseva E, Grigoryeva V, Zateyshchikov D, Gorbachev V, Chefranova Z, Dudarev M, Nilk R, Rozhdestvenskiy A, Brozman M, Gurcik L, Dvorak M, Krastev G, Kurca E, Vyletelka J, Brozman M, Kim JS, Kim JS, Bae HJ, Kim YW, Kim JT, Cha JK, Nam HS, Chang DI, Lee YS, Oh K, Yu SW, Sohn SI, Lee J, Cho HJ, Kim EG, Rha JH, Kim SH, Molina CA, Cateriano CM, Leal JS, Mora JV, Yañez MR, González JR, García FP, Cortina MG, Vallejo JM, Lara JA, Martín TS, Herrero JA, Ferrairó JI, Culleré JG, Álvarez FM, Wahlgren N, Steinberg A, Callander M, Laska AC, Bokemark L, Mooe T, Käll TB, Welin L, Sjöblom L, Hambraeus J, Teichert J, Wannberg H, Sanner J, Ramströmer B, Ziedén B, Hau SO, Gustafsson C, Michel P, Michel P, Kahles T, Lyrer P, Arnold M, Liesch M, Medlin F, Cereda C, Kägi G, Luft A, Carrera E, Lee TH, Lee TH, Po HL, Chern CM, Lien LM, Chan L, Liu CH, Wu SL, Lee JD, Chen CH, Lin HJ, Lin RT, Chen WH, Sun Y, Suwanwela NC, Suwanwela NC, Tantirittisak T, Muengtaweepongsa S, Nilanont Y, Tiamkao S, Udommongkol C, Watcharasaksilp K, Jantararotai W, Kutluk K, Kutluk K, Sirin H, Ince B, Asil T, Arsava M, Incesu TK, Tireli H, Kucukoglu H, Ak F, Unal A, Ozturk S, Uzuner N, Moskovko S, Chmyr G, Lebedynets V, Nikonov V, Shulga L, Smolanka V, Moskovko S, Khavunka M, Yavorska V, Tomakh N, Kozyolkin O, Litovaltseva G, Kasner S, Laskowitz D, Clark W, Lansberg M, Bernstein R, Brown D, Clark W, Dissin J, Graffagnino C, Harris J, Hicks W, Kasner S, Katzan I, Kramer J, Willey J, Silliman S, Starkman S, Thaler D, Tremwel M, Concha M, Rajamani K, Dandapani B, Silver B, Deal N, Chang I, Hassan A, Rudolph S, Fischer K, Kirshner H, Logan W, Mallenbaum S, Hefzy H, Latorre J, Levine S, Ciabarra A, Dafer R, Anyanwu B, Cherian L, Panezai S, Khanna A, Dodds J, Torbey M, Gebel J, Woo H, Chiu D, Androulakis X, Burgin W, Pineda M, Yilmaz E, Altafullah I, Boutwell C, Cruz-Flores S, Sapkota B, Fayad P, Jacoby M, Rafiq S, Salgado E, Lafranchise E, Felton W, Madhavan R, Zaidat O, Pieper C, Riviello R, Burnett A, Fischer M, Gentile N, Calder C, Dietrich D, Cross J, Blankenship L, Dafer R, Montoya L, Grogan W, Young M, Khan F, Campbell D, Daboul N, Espinoza A, Cullis P, Concepcion G, Wulff J, Afzal H, Jaffrani N, Reiter W, Arshad T, Lukovits T, Welker J, Chang FL, Badruddin A, Babikian V, Menon R, Sander J, Springer M, Nanda A, Mas L, Rajan R, Silverman B, Hefzy H, Huang D, Carpenter D, Clark J, Ching M, Santhakumar S, Gould J, Bansal V, Vidal G, Mikesell T, Brick J, French W, Shah Q, Holmstedt C, Ishag-Osman N, Kostis J, Shehadeh A, Sethi P, Imam A, Mccomas C, Tran D, Gebreyohanns M, Wiseman B, Malik M, Schwarcz A, Altschul D, Castaldo J, Alshekhlee A, Gancher S, Krish N, Nguyen-Huynh M, Tremwell M, Sharma J, Lee L, Neil W, Siddiqui F, Malek A, Romero C, Nguyen HT, Huy TN, Hoang H, Nguyen T, Nguyen A, Nguyen H.

Abstract

BACKGROUND:

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.

METHODS:

We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.

RESULTS:

During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.

CONCLUSIONS:

In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

PMID:
27160892
DOI:
10.1056/NEJMoa1603060
[Indexed for MEDLINE]
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