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N Engl J Med. 2008 Sep 18;359(12):1238-51. doi: 10.1056/NEJMoa0805002. Epub 2008 Aug 27.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.

Collaborators (1138)

Diener HC, Sacco R, Yusuf S, Cotton D, Gu V, Hermansson K, Lawton WA, Ounpuu S, Vander-Maelen C, Voigt T, Blank B, Hilbrich L, Wu Y, Albers G, Bath P, Bornstein N, Chan B, Chen ST, Cunha L, Dahlöf B, DeKeyser J, Donnan G, Estol C, Gorelick P, Kaste M, Lu C, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Weber M, Yoon BW, Machnig T, Humphreys M, Wolf P, Fisher M, Norrving B, Palesch Y, Sleight P, Turpie A, Buck T, Chong J, Dagenais G, delaPaz R, Diehl A, DiTullio M, Easton D, Ehrenfeld C, Elkind M, Fiebach J, Forsting M, Gizewski E, Gohs D, Halperin J, Haude M, Herz C, Homma S, Kastrup O, Krakauer J, Magun A, Maschke M, Mohr JP, Möller-Hartmann C, Mummel P, Pile-Spellman J, Rodriguez C, Sack S, Schlaak J, Schmermund A, von Kummer R, Wanke I, Weimar C, Wieneke H, Zoepf T, Diener HC, Bath P, Donnan G, Cotton D, Estol C, Hilbrich L, Humphreys M, Ounpuu S, Roberts R, Teal P, Toni D, Sacco R, Yusuf S, Bath P, Sacco R, Cotton D, Dahlöf B, Diener HC, Gorelick P, Roberts R, Weber M, Yusuf S, Hilbrich L, Estol C, Ameriso S, Baumann D, Cirio JJ, Coleman TS, Esnaola y-Rojas MM, Fraiman H, Gabrielli H, Garrote J, Garrote M, Loli P, Ferreiro JL, Lepera S, Pardal MF, Rey R, Ruiz A, Saredo G, Simonsini C, Zinnerman A, Donnan G, Bladin C, Crimmins D, Davis S, Frayne J, Hand P, Henderson R, Ingham N, Levi C, Parsons M, Read S, Schultz D, Slattery A, Williams M, Zavala JA, Horner S, Aichner F, Brainin M, Baumhackl U, Brücke T, Doppler W, Dorda V, Haring HP, Seiser A, Wege HW, Wille G, Willeit J, Blecic S, Thijs V, Bruneel B, Caekebeke J, De Klippel N, De Windt A, De Deyn PP, Desfontaines P, Dethy S, Dupuis M, Görner A, Jeangette S, Laloux P, Pandolfo M, Peeters A, Sheorajpanday R, Van Landegem W, Vermylen P, Vanhooren G, Willems C, Massaro AR, André C, Almeida AC, Brondani R, Carvalho JJ, Cendes F, de Freitas GR, Fábio SR, Friedrich MA, Martins M, Martins SC, Maulaz AB, Minelli C, Moro CH, Oliveira-Filho J, Rocha MS, Siqueira-Neto JI, Valiente R, Zétola VH, Teal P, Amir N, Anderson BA, Arts R, Bailey P, Bayer N, Beaudry M, Berger L, Boulanger JM, Brunet D, Collier T, Côté R, Daniels V, Demchuk A, Desai H, Fontaine AM, Gawel M, Gladstone D, Goldstein W, Hachinski V, Herbert F, Hesser K, Hink H, Ho K, Howse D, Kastelic K, Kostyrko P, Lapierre M, Lebrun LH, Mackey A, Maharaj M, Miners L, Minuk J, Moddel G, Mosewich R, Novak D, Penn A, Pesant Y, Pikl P, Rabinovitch A, Rabinovitch H, Sahlas D, Schanz C, Scott J, Selchen D, Sharma M, Shuaib A, Silva J, Silver FL, Spence D, Stefanelli M, Stoger S, Stokes T, Teitelbaum J, Veloso F, Verreault S, Voll C, Walker C, Walker S, Wiegner R, Winder T, Winger M, Woolfenden A, Lu C, Chen DW, Chen HB, Chen SD, Cheng Y, Chi ZF, Cui LY, Di Q, Deng F, Ding MP, Ding SJ, Ding XS, Fan DS, Fan W, Fan XB, Feng HL, Gong J, Gong T, Hong Z, Hou XJ, Hu XQ, Huang YN, Li CY, Li L, Li T, Li W, Li ZY, Lin H, Lin QY, Liu CF, Liu JR, Liu JR, Liu M, Liu R, Liu XF, Liu Y, Luo GG, Luo GQ, Miao JT, Miao L, Pang ZY, Qiu W, Shao B, Sun XJ, Wang DX, Wang F, Wang LJ, Wang SZ, Wang W, Wang YJ, Wu J, Xia J, Xu E, Xu HQ, Xu SB, Xu X, Yang QD, Yi X, Yu PM, Zeng GL, Zeng JS, Zhai Y, Zhang B, Zhang CY, Zhang H, Zhang SH, Zhang WW, Zhang YB, Zhang Y, Zhang Y, Zhao G, Zhao JH, Zhao J, Zhao XQ, Zhou GX, Zhou HD, Zhu GM, Zhu YC, Petersen P, Andersen G, Arlien-Soeborg P, Bach IC, Binzer M, Boysen G, Heick A, Homburg AM, Husted S, Iversen H, Krarup LH, Olsen TS, Overgaard K, Von Weitzel-Muders-Sivenius P, Kaste M, Hillbom M, Koivisto K, Männikkö M, Mustanoja S, Numminen H, Nuutinen J, Sivenius J, Ducrocq X, Leys D, Lucas C, Macian F, Milandre L, Neau JP, Saudeau D, Vespignani H, Voicu M, Zuber M, Busse O, Ahlers A, Allendoerfer J, Benecke R, Boy S, Dethlefs A, Dichgans M, Diener HC, Eicke M, Erbguth F, Gahn G, Gass S, Glahn J, Görtler M, Grau A, Griewing B, Grond M, Grotemeyer KH, Haan J, Hamann G, Harms L, Harscher S, Hetzel A, Hoferichter A, Huelsboemer HB, Ickenstein G, Kaps M, Kirchner M, Kunte H, Liepert J, Malessa R, Mewald Y, Müller-Jensen A, Nabavi D, Nedelmann M, Nueckel M, Poppert H, Rabe K, Regula J, Ringleb P, Rosenkranz M, Schaebitz WR, Schaberger I, Schlachetzki F, Schneider D, Schrader J, Sliwka U, Sobesky J, Soda H, Steinke W, Thomalla HG, Topka H, Treib J, Vry M, Warnecke T, Weber R, Weiller C, Wessel K, Wiethölter H, Witte O, Wuttig H, Iliopoulos I, Ellul I, Giannopoulos S, Karageorgiou C, Papathanasopoulos P, Vassilopoulos D, Voyaki S, Ng PW, Fung BH, Hui KF, Leung T, Mok V, Wong KS, Xavier D, Agarwal A, Agrawal RR, Anandan AM, Anandhi V, Babu GK, Bandishti S, Bhargava A, Bhargava N, Bharani A, Bhatt A, Chidambaram N, Dewan Y, Dinaker M, Joshi R, Joshi S, Kalanidhi A, Kalantri SP, Kothari S, Kumar A, Kumar P, Jain V, Mehndiratta MM, Mijar S, Mishra V, Murali S, Muralidharan RS, Murthy JM, Nair R, Narayanan JT, Panwar RB, Patel P, Poncha F, Prasad VV, Rath A, Reddy BC, Rohatgi A, Roy AK, Sadanandham S, Salam A, Sarma GR, Singh H, Singh Y, Shanmugasundaram S, Sharma S, Sivakumar S, Sundararajan R, Sundararajan T, Tukaram U, Umarani R, Varma S, Velmurugendran CU, Venkitachalam A, Verghese R, Vinayan KP, Vyas A, Wadia RS, Galvin R, Kelly P, O'Mahony D, Bornstein N, Assa-Meirov B, Gross B, Lampl Y, Mahagney A, Merzlyak O, Milo R, Rabey M, Shopin L, Streifler J, Tanne D, Telman G, Turiansky L, Weller B, Yarnitsky D, Provinciali L, Arnaboldi M, Bassi P, Bergamasco B, Carolei A, Cascone G, Chiodo Grandi F, Comi G, Consoli D, Corea F, Dudine P, De Falco FA, Gandolfo C, Giaccaglini E, Gobbi B, Inzitari D, Lembo G, Melis M, Mutani R, Natalé E, Neri G, Rasura M, Sacchetti ML, Semplicini A, Stornello M, Stramba-Badiale M, Sterzi R, Torcasio G, Toso V, Uchiyama S, Yamaguchi T, Chiba K, Fujino Y, Hattori F, Hattori K, Hirai O, Imamura A, Ishii K, Ishihara T, Isobe M, Ito K, Jinnouchi T, Kaido M, Kawamoto T, Kawanishi M, Kim I, Kitazawa K, Kotera M, Kujiraoka Y, Kurokawa S, Maeda Y, Matsumoto K, Matsumoto M, Matsumoto S, Nakagawa F, Nakajima Y, Obata T, Ohnishi H, Sato N, Seguchi T, Seki T, Shibagaki Y, Shitamichi M, Tabuchi A, Takahashi K, Takekawa M, Takimoto Y, Tanabe H, Taniguchi H, Tatsuoka Y, Toda K, Toriyama T, Yamazaki M, Yoshida H, Tan KS, Hassan T, Chong HT, Tan KS, Tharakan JK, Arauz A, Aguayo J, Cantu C, Espinoza C, Fernández-Vera J, Guzman J, León C, Leyva A, López M, López-Ruiz M, Reyes S, Ruiz J, Vazquez R, Villarreal J, De Keyser J, Aramideh M, Boiten J, Brouwers P, de Bruijn B, Franke C, den Heijer J, Dellemijn P, Hagemans J, Keizer K, Kok S, de Kort P, de Kruijk J, Kuipers-Lo Dico J, van Leusden J, van Leusen H, Jansen B, Mulleners WM, ten Napel K, de Rijk-van Andel JF, Van Remmen J, Rutgers W, Schonewille WJ, Simons T, Tacke TJ, Vries E, Wessel J, van Zagten M, Indredavik B, Naess H, Rohweder G, Røsjø Ø, Cunha L, Campillo J, Ferro JM, Lopes G, Pinto AA, Salgado V, Skvortsova V, Alifirova V, Amintaeva A, Antukhova O, Avakyan G, Belkin A, Belova A, Boiko A, Boiko A, Bulgakov V, Cherman M, Dokuchaeva N, Doronin B, Evzelman M, Fedin A, Fedorova N, Gileva O, Glezer M, Golikov K, Halo N, Isakova E, Ivleva A, Kabanova L, Kotov S, Kovalenko A, Kozin G, Lokshtanova T, Lutsky M, Magzhanov R, Martynov M, Mirsaev T, Mulyarov D, Narodova V, Odinak M, Orlov A, Parfenov V, Pizova N, Popova J, Poroshina E, Pronina S, Pryanikova N, Pynchuk E, Renzhina L, Savchenko A, Shirokov E, Shmyrev V, Sholomov I, Shmidt N, Simanenkov V, Skoromets A, Sorokoumov V, Spirin N, Stakhovskaya L, Stepanchenko A, Strachunskaya E, Stulin V, Suslina Z, Timerbaeva S, Trinitatsky Y, Varakin Y, Voskresenskaya O, Yacupov E, Yahno N, Yanishevsky S, Yudina G, Yudelson Y, Zhitkova J, Chan BP, Chang HM, Chen CC, Cheong W, De Silva DA, Gan RN, Meng C, Seah AB, Sharma VK, Soon CS, Venketasubramanian N, Wai Y, Wong MC, Yip CW, Smuts J, Francis P, Gardiner J, Guldenpfennig W, Lurie D, Mochan A, Retief C, Van Niekerk W, Yoon BW, Bang OY, Cho KH, Han SW, Heo JH, Kang DW, Kim HA, Kwon HM, Kwon JH, Kwon SU, Lee BC, Nam HS, Park MS, Rha JH, Yu KH, Gil-Nunez A, Alvarez-Sabín J, Antón C, Egido JA, Gállego J, Gracia F, Moltó JM, Navarro R, Rubio F, Wahlgren NG, Andersson B, von Arbin M, Berglund A, Bertholds E, Bokemark L, Carlstroem C, Elgåsen AC, Eriksson JP, Hansson PO, Käll TB, Lindgren A, Lökk J, Malm J, Markström I, Milovanovic M, Nilsson SA, Persson B, Skogar O, Stenstam M, Teichert J, Karlsson-Tivenius S, Von Euler M, Wallén T, Chen ST, Chang KC, Chang MH, Chang YJ, Chen CH, Chen WH, Chuang YT, Hsu CY, Hu HH, Huang YC, Hwang WJ, Jeng JS, Lee JT, Lien LM, Lin RT, Lin YJ, Liu CH, Peng GS, Po HL, Tan TY, Tsai SC, Wang SF, Wong WJ, Chankrachang S, Chinvarun Y, Chutinet A, Muengtaweepongsa S, Nilanont Y, Poungvarin N, Sithinamsuwan P, Suwanwela N, Tanprawate S, Bahar S, Aktan S, Bakar M, Balkan S, Dalkara T, Kutluk K, Ozdemir G, Moskovko S, Balyskyy O, Bitensky V, Dubenko O, Dzyak L, Goloborodko A, Grebenyuk G, Koselkin A, Kulgeyko V, Kuznetzova S, Lebedynets V, Maly V, Medvedkova S, Melnyk E, Mishchenko T, Moskovko G, Orzheshkovskyy V, Ovsyannikova N, Yavorska V, Yurdanova I, Zushkha V, Bath P, Brawn L, Brown M, Campbell L, Cohen D, Curless R, Davis J, Durward G, Ford G, Gray C, Hammonds FL, Hendra T, James M, Kalra L, Kumar R, Jackson S, Jenkinson D, Lees K, Lip G, MacWalter R, Muir K, Murphy P, Okwera J, Orugun E, Passmore P, Potter J, Sharma A, Sharma J, Sterling M, Ragab S, Robinson T, Roffe C, Rowe A, Turton J, Albers G, Gorelick P, Sacco R, Abbott F, Absher J, Acharya A, Adams H, Akins P, Albakri E, Alberts M, Alonso R, Altafullah I, Anderson E, Andrefsky J, Armstrong R, Arnold G, Arora A, Atkinson R, Azhar S, Bansil S, Becker K, Bell R, Benardo L, Bernardini G, Bernstein A, Blachman P, Boiser J, Boop B, Boutwell C, Bressler D, Brooks C, Brooks W, Calhoun R, Campanella F, Carlson S, Carpenter D, Castaldo J, Castaldo R, Cauli M, Chan K, Chaturvedi S, Cherian S, Chesser M, Chiu D, Clark W, Cleeremans B, Cohen S, Coin T, Collins L, Concha M, Cooper G, Couch J, Coull B, Crisostomo E, Cruz A, Cullis P, Dafer R, Dash S, Davis D, Davis P, DeMatteis J, Diamond B, Dick A, Dietrich D, Dunnigan R, Duong D, Edelsohn L, Ehrenfeld H, Elkins J, Englert M, Erlemeier S, Eubank G, Fayad P, Felberg R, Felton W 3rd, Ferguson R, Flitman S, Fonzetti P, Furie K, Garcia M, Gardziola G, Gebel J, Glass J, Goldstein L, Goldszmidt A, Goli S, Graham G, Graybeal D, Grayum B, Green E, Green J, Green P, Greer D, Gropen T, Gross J, Grotta J, Gunwardane R, Haake B, Habiger T, Halsey J, Hanley D, Hanna J, Hansen C, Hanson S, Harpold G, Harris J, Harris M, Hart R, Hedges K, Hendin B, Hinchey J, Ho J, Hoffman M, Hollander J, Holt W, Holzmacher K, Howell G, Howell S, Huang D, Hughes R, Hull R, Hwang T, Jacobson M, Jacoby M, Jayam-Trouth A, Jackson C, John K, Johnson-Finley B, Johnson M, Johnston S, Kamal A, Karanjia P, Kase C, Kasner S, Katz L, Katz P, Kent T, Kelley R, Kidwell C, Khanna A, Kirshner H, Kleindorfer D, Knox C, Kramer J, Labiche L, Lada R, LaFranchise EF, LaMonte M, Lee M, Lee-Kwen P, Leifer D, Leira E, Levin K, Libman R, Liebeskind D, Lindholm K, Livingstone JN 2nd, Locke G, Logan W, Luciano J, Lutsep H, Majid A, Mangeshkumar V, Markind S, Mate L, McCain J 4th, McElveen WA, McKown B, Merino J, Meyer B, Mikesell T, Mirsen T, Montoya L, Moon S, Moonis M, Moore K, Nasrallah J, Nassief A, Nelson M, Nichols F, Osborne J, Oser F, Ovbiagele B, Palestrant D, Panezai S, Papamitsakis N, Parry G, Perez M, Perkins C, Porter J, Preston W, Rabiee H, Raikhel M, Reichwein R, Remmel K, Richardson B, Ringel R, Rosenbaum D, Ross D, Rubin M, Ruffing K, Sachdev H, Sauter M, Saver J, Schafer J, Schiftan R, Schim J, Schleining AK, Schneck M, Selim M, Sen S, Shafer S, Shafran B, Sharfstein S, Sherman D, Sila C, Silliman S, Silver B, Silverman B, Silverman I, Singh R, Skillings N, Slivka A, Smith D, Soto R, Sparr S, Stephens R, Sullivan H, Sung G, Sutherland J, Syed A, Tabbaa M, Tamulonis D, Taylor R, Tesfaye D, Thomas T, Tietjen G, Todorov A, Torbey M, Tolge B, Tremwell M, Truax W, Unwin D, Vaishnav A, Varma N, Venkatesh YS, Verro P, Verson R, Vidic T, Vrooman P, Wallis R, Wang D, Wang J, Waters M, Wechsler L, Weinberger J, Weissman J, Wheatley G, Whitehead R, Willhite A, Willis H, Wilson E, Wilson R, Wilterdink J, Wirkowski E, Wozniak M, Wright C, Young M, Zachariah S, Zuckerman S, Zweifler R.

Author information

  • 1Miller School of Medicine, University of Miami, Miami, USA.

Abstract

BACKGROUND:

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.

METHODS:

In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.

RESULTS:

A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).

CONCLUSIONS:

The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

2008 Massachusetts Medical Society

Comment in

PMID:
18753638
[PubMed - indexed for MEDLINE]
PMCID:
PMC2714259
Free PMC Article

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