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Lancet Neurol. 2012 Jun;11(6):503-11. doi: 10.1016/S1474-4422(12)70092-3. Epub 2012 May 8.

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

Collaborators (1129)

Granger CB, Wallentin L, Alexander JH, Ansell J, Diaz R, Easton JD, Gersh BJ, Hanna M, Horowitz J, Hylek EM, McMurray JJ, Mohan P, Verheugt FW, Diaz R, Bahit MC, Aylward P, Amerena J, Huber K, Bartunek J, Avezum A, Ezekowitz JA, Dorian P, Lanas F, Lisheng L, Zhu J, Isaza D, Jansky P, Husted S, Harjola VP, Steg PG, Hohnloser SH, Keltai M, Pais P, Xavier D, Lewis BS, De Caterina R, Goto S, Hermosillo AG, Alings AM, Atar D, Segura L, Ruzyllo W, Vinereanu D, Varshavsky S, Golitsyn S, Oh BH, Commerford P, Lopez-Sendon JL, Rosenquist M, Erol C, McMurray JJ, Parkhomenko A, Flaker G, Garcia D, Pfeffer MA, Diener HC, Maggione A, Pocock S, Rouleau JL, Wyse G, Alexander JH, Al-Khatib S, Lopes RD, Held C, Hylek EM, Bushnell C, Terent A, Leonardi S, Subherwal S, Eapen Z, Vavalle J, Zomorodi A, Kolls B, Berger J, Vergara J, Parikh D, Zia S, Stashenko G, Lombardi C, Matthews R, Hagstrom E, Akerblom A, Varenhorst C, Berntsson SG, Stenborg A, Lundstrom E, Guimaraes H, Flato U, Nacif S, Barros P, Echenique L, Rodrigues P, Armaganijan L, Lopes AC, Albrecht A, Vico M, Mackinnon I, Vogel D, Vico M, Gabito A, Cassettari A, Zaidman C, Montaña O, Hrabar A, Jure H, Lastiri H, Poy C, Caccavo A, Cuneo C, Colombo H, Rolandi F, Hershson A, Garrido M, Sanchez A, Bruno ML, Piskorz D, Cuadrado J, Hasbani E, Serra J, Cartasegna L, Schygiel P, Muratore C, Marino J, Sosa Liprandi MI, Guerrero RA, Ramos H, Mercado D, Guzman L, Beneitez C, Estepo J, Torrijos R, Retyk E, Vita N, Luciardi H, Casey M, Orlando S, Labarta MB, Santos D, Amerena J, Purnell P, Horowitz J, Salem H, Liu A, Zimmet L, Roger S, de Looze F, de Looze F, Lehman R, de Looze F, Jackson B, Ashby D, Heddle W, Rogers J, Brieger D, Martin P, Cross D, Walters D, Waites J, Counsell J, Lowy A, de Looze F, Huber K, Stockenhuber F, Pieske B, Striekwold H, Wollaert B, Nachtergaele H, Vijgen J, El Allaf D, Mairesse G, Boxho G, De Deyn PP, Vanderheyden M, Semeraro O, Desfontaines P, Leroy J, Provenier F, Bruneel B, Vrolix M, Peeters A, Deceuninck O, Saraiva JF, Reis G, Rossi P, Zimmermann S, Jaber J, Botelho R, Manenti E, Jorge J, Maia L, Leães P, Villaça Guimaraes Filho F, Fichino M, De Paola A, Indio do Brasil CK, Albuquerque D, Bodanese L, Matsubara L, Mourilhe Rocha R, Genta P, Meneghelo Z, Oliveira L, Lorga Filho A, Garbelini B Jr, Oliveira G, Teixeira M, Precoma D, Pelloso E, Muniz A, Valéria Braile MC, Ueda R, Rabelo Alves A Jr, Pimentel Filho P, Zimerman L, Coutinho M, Silveira J, Reis H, Moreira D, Paiva M, Aziz JL, Gois J, Dutra O, Yao L, Syan G, Coutu B, Chehayeb R, Sabe-Affaki G, Fortin C, Borts D, Bhargava R, Fell D, Cha J, Pandey A, Boucher P, Sabbah E, Ma P, Talbot P, Spence D, Wade A, Green M, Berlingieri J, Vizel S, Chan YK, Blostein M, Talajic M, Sterns L, Grondin F, Hruczkowski T, Labonte R, O'Mahony M, Rupka D, Mangat I, Dowell A, Kelly A, St Maurice F, Henein S, Saunders K, Lasko B, Sami M, MacKinnon R, Rizvi Q, O'Keefe D, Ricci J, Gervais B, Hart R, Bose S, Nawaz S, Connors S, Winkler L, Boileau M, Healey J, Collette R, Rebane T, Ramjattan B, Senior R, Therrien R, Wells P, Raffo C, Cobos J, Potthoff S, Stockins B, Pincetti C, Corbalan R, Vejar M, Potthoff S, Li W, Zhao S, Chen X, Wu S, Tan H, Wu S, Qu P, Jiang X, Wei M, Yang X, Li J, Ma S, Gu S, Dai QY, Li L, Yu B, Yin Y, Wang N, Gao L, Zhou SX, Wang JA, Li ZQ, Bai F, Zhang F, Lu G, Chen Y, Zhang Y, Jiang D, Zonggui W, Li H, Cao K, Lu Q, Li L, Hu T, Li H, Wang X, Botero R, Reyes A, Jaramillo N, Urina M, Velez S, Gomez E, Pava L, Isaza D, Dunaj M, Hudcovic M, Jerabek O, Brat R, Spinar J, Dedek V, Zidkova E, Podpera I, Cech M, Gorican K, Micko M, Stribrna M, Frost L, Torp-Pedersen C, Toftager Larsen C, Tuxen C, May O, Pedersen KE, Jensen G, Nielsen T, Nyvad O, Husted S, Gilså Hansen M, Egstrup K, Lomholdt J, Skagen K, Joen Jakobsen T, Olsen M, Grande P, Melin J, Tynni M, Harjola VP, Strand J, Parikka H, Jääskeläinen T, Corbelli JL, Gosse P, Mirode A, Mansourati J, Lavabre G, Defaye P, Steg PG, Kahrmann G, Horacek T, Bauer A, Spitzer S, Schlegl M, Winkelmann B, Vöhringer HF, Stenzel G, Haverkamp W, Harenberg J, Schumacher M, Wunderlich J, Natour M, Rieker W, Gass S, Brachmann J, Jung J, Poppert H, Häge R, Lickfett L, Schoeller R, Goedel-Meinen L, Utech A, Buerke M, Maschke M, Haberl R, von Hodenberg E, Griewing B, Schlachetzki F, Hamer H, Hoch T, Zabel M, Jordan R, Stögbauer F, Hetzel A, Weimar C, Schauerte P, Fischer D, Mügge A, Bittersohl A, Mügge A, Lee K, Yu C, Lakatos F, Vértes A, Kovács A, Takács J, Pálinkás A, Bakai J, Papp A, Illés Á, Tomcsányi J, Szakál I, László Z, Katona A, Jobbágy L, Keltai K, Dézsi C, Lupkovics G, Cziraki A, Mohácsi A, Simon K, Gupta S, Agarwal D, Fulwani M, Naik A, Nambiar A, Chidambaram N, Srinivasasastry B, Joseph J, Padinhare M, Khanna P, Grant P, Arneja J, Gadkari M, Garg N, Pothineni RB, Sathe S, Ramesh S, Malipeddi B, Bharani A, Gowdappa HB, Prakash VS, Dharmadhikari A, Bhandari S, Desai N, Banerjee S, Ghaisas N, Ramagiri B, Sinha S, Gojanur G, Duggal J, Jain V, Dani S, Singh P, Srikanthan V, Puri VK, Gopal R, Viskin S, Shochat M, Hayek T, Reisin L, Rosenheck S, Lewis B, Zimlichman R, Weiss A, Marmor A, Turgeman Y, Klainman E, Francis A, Lahav M, Omary M, Morris M, Olivieri C, Santonastaso M, Fenici R, Mos L, Ghirarduzzi A, De Caterina R, Novo S, Richiardi E, Testa S, Pini M, D'Angelo A, Barsotti A, Donati M, Chiariello M, Galli M, Casolo G, Moretti L, Atsushi Y, Yamamoto K, Goto S, Kihara H, Akihiko T, Saito T, Yoshii H, Sasaki T, Suwa M, Adachi S, Usada K, Nakamura Y, Hayashida K, Yamada T, Iwasawa T, Kawase Y, Sugi K, Murakami T, Satake K, Iwao T, Maemura K, Koretsune Y, Tsubokou Y, Yamashita M, Sato Y, Kouichi F, Yura S, Matsushima A, Iwade K, Kamakura S, Tanaka S, Murata H, Yamamoto S, Kobayashi Y, Higashi Y, Shinozaki T, Ikeda H, Hisaoka T, Node K, Takagi H, Ong TK, Abidin IZ, Yusof Z, Yusoff K, Maskon O, De los Rios Ibarra M, Alcocer Gamba M, Lopez Rosas E, Calvo Vargas C, Fajardo Campos P, Cordero-Cabra JA, JerJes-Sanchez C, Hernandez Santamaria I, Molina L, Olvera Ruiz R, Arean Martinez C, Gonzalez Guerra J, Morales Gonzalez I, Cervantes-Escarcega J, Chuquiure-Valenzuela EJ, Riojas C, Gonzalez Hermosillo J, Galicia A, Nierop P, Verheugt F, Daniels M, Lok D, Alings A, Scholten M, Plomp J, Derksen R, Bredero A, Zwart P, Schaap A, Michels H, Van der Zwaan C, Hysing J, Elle S, Omland T, Rønnevik P, Øie B, Otterstad JE, Bogale N, Kjærnli T, Halvorsen S, Bryhni B, Vikenes K, Cabrera W, Rodriguez A, Chavez C, Gamboa R, Segura L, Araoz O, Azanero R, Toce L, Medina F, Bustamante G, Rios Vasquez C, Zubiate M, Collado F, Morales-Palomares E, Sy R, Morales D, Rogelio G, Abola MT, Ramos E, Yamamoto M, Collado F, De Leon F, Abelardo N, Kania G, Szpajer M, Rajzer M, Janion M, Bronisz M, Ruzyllo W, Piepiorka M, Wendland M, Czerski T, Korzeniak R, Budaj A, Wawrzynska L, Ogorek M, Miekus P, Tracz W, Ocicka-Kozakiewicz A, Stepinska J, Kiedrowicz Z, Pasierski T, Kasprzak J, Galewicz M, Podogrodzka B, Krauze-Wielicka M, Chmielinski A, Boruczkowska-Kaszkowiak A, Piotrowski W, Vinereanu D, Stamate S, Cinteza M, Tanaseanu CM, Dan GA, Benedek I, Ionescu RM, Lighezan D, Salajan A, Carasca E, Capalneanu R, Pop C, Fierbinteanu-Braticevici CG, Zdrenghea DT, Gaita D, Manitiu I, Nanea T, Arsenescu Georgescu C, Chizhov P, Kastanayan A, Oleynikov V, Treshkur T, Govorin A, Zhelninova T, Barbarash O, Novikova T, Reshetko O, Sivkova E, Obrezan A, Panchenko E, Popov S, Ivleva A, Zotov D, Gordienko A, Kamalov G, Chernichka I, Levin A, Zrazhevsky K, Golitsyn S, Shilkina N, Golovach A, Filonenko G, Bondarev S, Orlov V, Bragina A, Koziolova N, Svistov A, Shustov S, Libov I, Kisliak O, Privalova E, Aleksandrov O, Mazur E, Karpov Y, Belenky D, Kostenko V, Shubik Y, Ruda M, Arutyunov G, Eltishcheva V, Sidorenko B, Oseshnyuk R, Boyarkin M, Pozdnyakov Y, Staxhinskiy N, Sinopalnikov A, Yakushin S, Koniakhin A, Yarohno N, Sizova Z, Zadionchenko V, Klimov I, Duplyakov D, Kanorsky S, Mareev V, Terekhov V, Arkhipov V, Sotnikova T, Yakusevich V, Lesnov V, Gordeev I, Gratsiansky N, Shalaev S, Sulimov V, Talibov O, Zemtsovsky E, Azarin O, Tan RS, Thorne J, De Jong D, Basson M, van Zyl L, Commerford P, Weich H, van Nieuwenhuizen E, Roos J, Kelbe D, Viljoen J, Hong TJ, Oh BH, Park KS, Jeong MH, Rhim CY, Choi DJ, Sung JH, Kim YN, Bae JH, Tahk SJ, Ryu KH, Kwon SU, Rho TH, Cha TJ, Shin DG, Álvarez García P, Vida M, Galve E, Bruguera J, Roquer J, Olías de la Cruz F, Paz Bermejo MA, Segura T, Gómez Gómez JH, Ugarriza A, Plaza Pérez I, Villacastin J, Bertomeu V, Vargas R, Serena Leal J, Egido Herrero J, Bethencourt González A, Albert X, Gonzalez Juanatey C, Medrano V, Vivancos J, Andersson T, Lindholm CJ, Al-Khalili F, Höglund C, Rosenqvist M, Bergström O, Herlitz J, Rasmanis G, Johansson L, Christersson C, Fredholm O, Al-Khalili F, Callander M, Po H, Pan JP, Tseng CD, Shyu KG, Chu SH, Kultursay H, Gorenek B, Erol C, Lip G, Albazzaz M, Kadr H, Cohen A, Cooke J, Agarwal A, Brack M, Pye M, Anderson M, Dunn F, Wong YK, Glen S, Ford G, Alwail A, Yousef Z, Blagden M, Murdoch D, McInnes G, Camm J, Ridsdill Smith W, McMurray JJ, Senior R, Webster J, Dutka D, McClements B, Yousef Z, Levy T, Yogasundram S, Moriarty A, McCullagh M, Flather J, Gumbley M, Findlay I, Davies J, Cooke A, Ahsan A, Cannon J, Bakhai A, Jacob A, Trouton T, Ajala A, Bartkowiak A, Humiston D, Kufs W, Klancke K, Jetty P, Gupta D, Nadar V, Yousuf K, Sosa-Suarez G, Gill S, Wukelic M, Mayer N, Colan D, Haskel E, Grena P, Haught W, Walsh R, Carr K, Tahirkheli N, Jardula M, Cebe J, Bloom S, Bilazarian S, Gilmore R, Jaffrani N, Goldscher D, Lebowitz A, Friedlander I, Stein M, Promisloff S, Magnano A, Dean J, Gerber J, Perloff D, Cohen Y, Meholick A, Tobin T, Acheatel R, Levanovich P, Ip J, Porterfield J, Seshadri N, McKenzie M, Alfieri A, Gazmuri R, Beanblossom B, Van Hamersveld D, McCriskin J, Gelernt M, Bowden W, Sotolongo C, Lang J, Kaatz S, Agnone F, Hassman D, Flores E, Albrecht F, Hassel C, Quartner J, LaFata J, Bedwell N, Herzog W, Amin J, Usedom J, 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Rodriguez-Fierro C, Hattler B, Rubin M, Hartley P, Tami L, Ball E, McPherson C, Eisenberg S, Niazi I, Orlov M, Bachhuber B, Massey C, Phillips W, Mouhayar E, Griffin J, Blumberg E, Slabic S, Danisa K, Samal A, Rohrbeck S, McCullough P, Dohan D, Aycock G, Jones A, Anderson J, Silverman R, Smith W, Mishkel D, Patterson N, Moore H, Kabour A, Muttreja M, Jaffrani W, Vidic T, Kent S, Platt B, Goldberg R, Kulback S, Patel R, Bazzi A, Goldman S, Roman A, Levin C, Lachterman B, Chandrashekhar Y, Aisiku I, Powers C, Engeron E, Bernstein R, Shah S, Strobel J, Punatar H, Garcia R, Linden D, Al-Mudamgha A, Quick A, Kramer J, Feldman G, Stapleton D, Davis M, Graff J, Galizia J, Wassmer P, Chiu D, Ison R, Curry K, Finneran M, Solomon A, Schifferdecker B, Seger J, Alexander A, Yates S, Ashley R Jr, Cordero-Sepulveda J, Cowen P, Ayres T, Kowalski B, Anton S, Phillips J, Donovan D, Patel A, Smith R, Updegrove J, Buxton A, Clark D, Margolis J, Brooks G, Pernenkil R, Walters J, Richards M, Maccaro P, 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Author information

  • 1Department of Neurology, University of California-San Francisco, San Francisco, CA 94143-0114, USA. eastonjd@neurology.ucsf.edu

Erratum in

  • Lancet Neurol. 2012 Dec;11(12):1021.

Abstract

BACKGROUND:

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA.

METHODS:

Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984.

FINDINGS:

Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA.

INTERPRETATION:

The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population.

FUNDING:

Bristol-Myers Squibb and Pfizer.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Comment in

PMID:
22572202
[PubMed - indexed for MEDLINE]
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