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    Lancet Neurol. 2008 Oct;7(10):875-84. Epub 2008 Aug 29.

    Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.

    Collaborators (1138)

    Diener HC, Sacco R, Yusuf S, Blank B, Cotton D, Gu V, Hermansson K, Hilbrich L, Humphreys M, Lawton WA, Machnig T, Ounpuu S, VanderMaelen C, Voigt T, 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, Lv C, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, Weber M, Yoon BW, 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 H, Rabinovitch A, 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, Lv 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-Mudersbach 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, H 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 Keysern 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 O, 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.

    Source

    Department of Neurology, University of Duisburg-Essen, Essen, Germany. h.diener@uni-essen.de

    Erratum in

    • Lancet Neurol. 2008 Nov;7(11):985.

    Abstract

    BACKGROUND:

    The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

    METHODS:

    Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062.

    FINDINGS:

    20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups.

    INTERPRETATION:

    Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

    PMID:
    18757238
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2772657
    Free PMC Article

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