1. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial
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Scott E Kasner, Balakumar Swaminathan, Pablo Lavados, Mukul Sharma, Keith Muir, Roland Veltkamp, Sebastian F Ameriso, Matthias Endres, Helmi Lutsep, Steven R Messé, J David Spence, Krassen Nedeltechev, Kanjana Perera, Gustavo Santo, Veronica Olavarria, Arne Lindgren, Shrikant Bangdiwala, Ashkan Shoamanesh, Scott D Berkowitz, Hardi Mundl, Stuart J Connolly, Robert G Hart, N Abdelhamid, D Abdul Rahman, M Abdul-Saheb, P Abreu, M Abroskina, F Abu Ahmad, S Accassat, M Acciaresi, A Adami, N Ahmad, F Ahmed, M Alberto Hawkes, F Alemseged, A Ali, R Altavilla, L Alwis, P Amarenco, S Amaro, LE Amaya Sanchez, A Amelia Pinto, SF Ameriso, H Amin, T Amino, AK Amjad, E Anagnostou, G Andersen, C Anderson, DC Anderson, M Andrea Falco, F Andres Mackinnon, D Andreu, M Androulakis, M Angel Gamero, G Angel Saredo, R Angeles Diaz, M Angels Font, S Anticoli, A Arauz, AA Arauz Gongora, P Araya, JF Arenillas Lara, S Arias Rivas, M Arnold, S Augustin, W Avelar, E Azevedo, V Babikian, A Bacellar, K Badalyan, HJ Bae, EM Baez Martinez, H Bagelmann, P Bailey, Z Bak, M Baker, A Balazs, D Baldaranov, I Balogun, T Balueva, Z Bankuti, M Bar, A Baranowska, J Bardutzky, S Barker Trejo, J Barlinn, F Baronnet, C Barroso, M Barteys, T Bartolottiova, A Barulin, M Bas, S Bashir, V Basile, R Bathe-Peters, R Bathula, C Batista, H Batur Caglayan, P Baumgartner, R Bazan, O Bazhenova, M Beaudry, J Beer, Y Behnam, C Beilei, A Beinlich, Y Bejot, A Belkin, OR Benavente, A Benjamin, V Berardi, D Bereczki, SD Berkowitz, J Berlingieri, W Berrios, J Berrouschot, M Bhandari, M Bhargavah, H Bicker, T Bicsak, M Bilik, D Bindila, J Birchenall, L Birnbaum, T Black, D Blacker, D Blacquiere, C Blanc-Labarre, C Blank, B Blazejewska-Hyzorek, S Bloch, E Bodiguel, E Bogdanov, L Boos, L Borcsik, N Bornstein, S Bouly, G Braga, I Bragado, MC Bravi, C Brokalaki, W Brola, R Brouns, D Bruce, J Brzoska-Mizgalska, B Buck, M Buksinska-Lisik, J Burke, M Burn, G Bustamante, L Cabrejo, K Cai, S Cajaraville, M Calejo, D Calvet, J Campillo, E Campos Costa, P Camps, H Can Alaydin, E Candeloro, C Canepa, CG Cantu Brito, M Cappellari, C Carcel, P Cardona Portela, F Cardoso, M Carek, M Carletti, J Carlos Portilla, P Caruso, I Casado-Naranjo, P Castellini, D Castro, F Castro Meira, A Cavallini, N Cayuela Caudevilla, S Cenciarelli, C Cereda, P Cerrone, A Chakrabarti, P Chaloulos-Iakovidis, A Chamorro, D Chandrasena, DI Chang, C Che, J Chembala, J Chen, Z Chen, T Chen, H Chen, X Chen, G Chen, L Chen, S Chen, B Cheripelli, M Chin, E Chiquete Anaya, M Chorazy, H Christensen, T Christensen, L Christian, F Chu, CS Chung, W Clark, R Clarke, S Claverie, E Clemente Agostoni, B Clissold, J Coelho, D Cohen, S Colakoglu, D Collas, R Condurso, SJ Connolly, D Consoli, C Constantin, AB Constantino Silva, L Contardo, A Corlobe, M Correia, C Correia, E Cortijo Garcia, B Coull, S Coutts, S Coveney, P Cras, R Crols, S Crozier, A Csanyi, L Csiba, K Csontos, R Csuha, L Cui, L Cunha, S Curtze, M Czerska, A Czlonkowska, M Czurko, M Czuryszkiewicz, M Dagnino, C Dai, A Daineko, G Dalek, D Damgaard, A Danese, K Dani, V Danku, W Dario Toledo, A Dávalos, A De Havenon, J De Keyser, N De Klippel, J De La Torre, A De Pauw, A De Smedt, R De Torres, MM De Vries Basson, J Dearborn, R Deganutto, M Degeorgia, I Deguchi, A Del Giudice, C Delcourt, R Delgado-Mederos, G Della Marca, B Delpont, S Deltour, DL Demets, M Dennis, J Desai, J Devine, I Dhollander, MT Di Mascio, M Diaconu, F Diaz Otero, J Dietzel, E Diez-Tejedor, N Ding, J Ding, M Diomedi, P Dioszeghy, M Distefano, V Domigo, E Dorodnicov, D Dossi, F Doubal, I Druzenko, P Du, J Du, T Duman, Y Duodu, D Dutta, L Dylewicz, J Eckstein, E Ehrensperger, S Ehrlich, G Einer Allende, B Elena Halac, S Elyas, M Endres, JM Engelbrecht, S Engelter, M Epinat, F Eren, M Esbjornsson, B Escribano, I Escudero, B Esisi, B Essa, M Esterbauer, N Evans, D Eveson, S Fabio, L Fang, S Fanta, M Fares, M Fatar, K Faust, A Favate, F Fazekas, M Federica Denaro, A Fedin, P Felipe Amaya, J Feng, K Ferencova, M Fernanda Gilli, MD Fernandez, PN Fernandez Pirrone, J Fernandez Vera, J Ferrari, A Ferreira, G Ferreira Junior, M Fidler, D Field, T Field, C Figueroa, J Fiksa, A Filipov, A Firstenfeld, L Fisch, U Fischer, M Fisselier, U Fiszer, F Fluri, G Fortea, K Fotherby, A Fraczek, E France, G Freitas, S Frey, M Frick, A Friedman, M Friedrich, G Frisullo, W Fryze, B Fuentes Gimeno, H Fujigasaki, K Fukuyama, A Furlan, G Furlanis, J Furnace, M Gabriel, E Gabriel Reich, RJ Gagliardi, F Galati, E Galli Giqueauk, A Gallina, E Gallinella, J Gallo, S Gangadharan, Y Gao, R Garcia Lopez, A Garcia Pastor, SM Garcia Sanchez, M Garnauf, P Garnier, D Gasecki, K Gasic, K Gasiorek, S Gasser, M Gaugg, M Gebreyohanns, K Gebura, J Geng, M Geniz Clavijo, K Georg Haeusler, R Geran, M Geremek, Z Gerocs, D Ghia, D Giannandrea, F Giatsidis, JA Gien Lopez, A Gil Nunez, L Gimenez, E Giralt, A Glabinski, D Gladstone, M Gliem, M Gluszkiewicz, R Goddeau, E Gogoleva, M Gokce, D Goldemund, K Golikov, A Gomes Neto, M Gomez Schneider, M Gomez-Choco, M Gomis, JF Gongora-Rivera, Y Gonysheva, L Gonzalez, ME Gonzalez Toledo, M Gottschal, I Gozdzik, S Grabowski, S Graf, D Green, D Greer, T Gregorio, S Greisenegger, I Greshnova, M Griebe, M Grzesik, J Guan, S Guarda, A Gueguen, C Guidoux, P Guillermo Povedano, B Guillon, V Guiraudg, G Gunathilagan, N Guryanova, V Gusev, G Gustavo Persi, R Gutiérrez, P Guyler, N Gyuker, V Hachinski, A Hajas, H Hallevi, G Hankey, GJ Hankey, L Hanouskova, L Hao, K Haraguchi, Y Haralur Sreekantaiah, S Haratz, D Hargroves, K Harkness, P Harmel, M Harrasser, RG Hart, M Harvey, R Hasan, Y Hasegawa, A Hassan, M Hattori, A Hatzitolios, M Hauk, T Hayashi, H Hayhoe, VS Hedna, M Heine, V Held, S Hellwig, J Henkner, N Henninger, S Hermans, J Hernandez, D Herrero, M Hervieu-Begue, R Herzig, L Hicken, M Hieber, M Hill, M Hirose, MC Hobeanu, B Hobson, M Hochstetter, J Hoe Heo, M Hoffmann, C Holmstedt, P Hon, KS Hong, Y Honma, A Horev, G Horgan, L Horvath, M Horvath, C Hoyer, D Huang, H Huang, B Huber, J Huhtakangas, M Hussain, S Igarashi, AM Iglesias Mohedano, J Ignacio Tembl, M Impellizzeri, Y Inanc, P Ioli, A Irina Aniculaesei, K Ishida, R Itabashi, H Iversen, A Jagolino, K Jakab, S Jander, H Janka, J Jankovych, J Jansen, L Jasek, M Javier Alet, L Javor, X Jin, P Jing, B Joachim, M Joan Macleod, M Johnson, J Jose Martin, C Joyner, K Judit Szabo, A Jun-Oconnell, R Jura, B Kaczorowska, J Kadlcikova, T Kahles, N Kakaletsis, I Kakuk, K Kalinowska, K Kaminska, C Kaneko, I Kanellos, P Kapeller, K Kapica-Topczewska, O Karasz, M Karlinski, JE Karlsson, K Kasa, E Kashaeva, SE Kasner, M Kaste, J Kasza, A Katalin Iljicsov, M Katsurayama, S Kaur, M Kawanishi, S Kaygorodtseva, K Ke, A Kei, J Keilitz, J Kellner, P Kelly, S Kelly, D Kemlink, M Kerekgyarto, I Keskinarkaus, D Khairutdinova, A Khanna, A Khaw, M Kholopov, C Khoumri, S Kirpicheva, H Kirshner, K Kitagawa, S Kittner, R Kivioja, F Klein, D Kleindorfer, T Kleinig, P Klivenyi, S Knecht, Y Kobayashi, A Kobayashi, M Koch, L Koehler, M Koivu, V Kolianov, I Koltsov, T Kondo, I Konkov, S Kopecky, E Korompoki, J Korpela, K Kosarz-Lanczek, A Koutroubi, K Kovacs, T Kovacs, H Kovacs, K Kowalczyk, M Kowalska, D Krajickova, M Kral, C Krarup Hansen, J Kraska, S Krebs, V Krejci, C Kremer, R Kreuzpointer, M Krzyzanowska, D Kucken, A Kulakowska, J Kunzmann, N Kurenkova, A Kuris, I Kurkowska-Jastrzebska, N Kurtenkova, O Kurushina, G Kusnick, M Kustova, T Kuwashiro, J Kwan Cha, A Lago, M Lagutenko, B Lajos, J Lambeck, C Lamy, A Landolfi, S Lanfranconi, W Lang, LB Lara Lezama, B Lara Rodriguez, T Largo, A Lasek-Bal, L Latte, V Lauer, P Lavados, R Le Bouc, R Leal Cantu, H Lechner, K Lecouturier, S Leder, J Lee, BC Lee, A Leger, E Leira, I Leisse, R Leker, G Lembo, L Lenskaya, J Leyden, G Li, M Li, S Li, J Li, G Liamis, H Liang, Z Liang, N Ligot, H Lin, R Lindert, A Lindgren, M Linna, T Litwin, K Liu, X Liu, L Llull, B Lohninger, M Longoni, C Loomis, D Lopes, M Lopez Fernandez, N Lopez Garza, A Lord, S Louw, R Lovasz, T Lowenkopf, Z Lu, SC Lubke-Detring, R Luder, S Lujan, B Luo, L Lupinogina, G Luschin, H Lutsep, A Lvova, J Ly, G.M. Grosse, H Ma, C Ma, M Machado, C Machado, S Macher, J Machetanz, F Macian-Montoro, E Mackey, A Mackey, G Maclean, J Maestre-Moreno, A Magadan, T Magyar, A Mahagney, A Majid, A Majjhoo, K Makaritsis, J Mandzia, M Mangas Guijarro, D Mangion, E Manios, S Mann, L Manning, C Manno, J Manuel Garcia, V Maqueda, M Mar Castellanos, M Mar Freijo, C Marando, S Marcela Lepera, J Marcos Couto, G Maria Bruera, L Maria Greco, A Maria Lorenzo, S Maria Obmann, A Maria Roa, C Marini, I Marinkovic, G Mario Sumay, C Mario Torres, M Marko, S Markova, H Markus, R Marsh, E Marsili, M Marta Esnaola, J Marta Moreno, J Marti-Fabregas, S Martina Angelocola, P Martínez Sánchez, N Martinez-Majander, S Martins, O Marzelik, S Mastrocola, G Matamala, A Matoltsy, B Matosevic, S Matsumoto, A Maud, G Mauri Cabdevila, Z May, Y Mayasi, A Mayr, T Mazzoli, K Mcarthur, L Mccullough, CE Medina Pech, F Medlin, M Mehdiratta, S Mehta, D Mehta, B Mehta, M Melis, E Melnikova, B Mendez, T Mendonca, JJ Mengual Chirifie, N Menon, A Mensch, E Meseguer, S Messe, K Metcalf, N Meyer, F Michas, N Micheletti, R Mikulik, H Milionis, B Miller, T Milling, C Minelli, J Minhas, M Minns, D Mircea, S Mishra, A Mismas, A Mistri, N Mitrovic, H Miyake, B Modrau, A Moey, C Molina, J Molina, A Molis, J Moller, S Molnar, F Moniche, C Monosi, V Monzani, M Moonis, R Morais, L Morales, A Morales, D Morar-Precup, F Moreton, C Moro, E Morozova, M Morton, T Morvan, E Morvan, T Motko, A Mowla, E Mozhejko, G Muddegowda, O Mudhar, T Mueller, C Muhl, KW Muir, H Mundl, S Munoz, C Murphy, S Murphy, A Murtuzova, T Musuka, J Mutzenbach, M Myint, W Mysliwy, M Naccarato, G Naeije, Y Nagakane, I Natarajan, D Navaratnam, A Nave, B Nazliel, K Nedeltchev, J Nel, H Nell, R Nemeth, L Nemeth, O Neto, K Ng, J Ngeh, L Nicolas Chialvo, T Nieminen, M Nikkanen, J Nikl, M Nikoforova, S Nishino, Y Nishiyama, X Njovane, S Nogawa, F Nombela, B Norrving, K Nosek, B Nowak, E Nowakowska-Sledz, G Ntaios, H Numminen, F Nunez, M Obadia, S Oberndorfer, A Obrezan, J Ochiai, W Oczkowski, MJ O'Donnell, A Odyniec, K Oh, M Ohira, Y Okamoto, M Okpala, S Okubo, L Olah, V Olavarria, J Oleszek, N Onat Demirci, V Ondar, G Ongun, K Ooyama, V Orosz, R Ortiz, G Osseby, E Österlund-Tauriala, C Ovesen, S Ozcekic Demirhan, J Ozdoba-Rot, S Ozturk, E Ozyurt, M Pablo Grecco, G Pablo Povedano, M Paciaroni, C Padiglioni, J Pagola, W Palasik, G Panczel, L Panos, G Papadopoulos, E Papadopoulou, A Papagiannis, V Papavasileiou, M Papina, JR Pardo De Donlebun, V Parisi, JM Park, J Pasten, N Patel, O Pavlik, M Pawelczyk, WF Peacock, H Pei, T Peisker, LF Pena Sedna, A Penn, S Pentek, E Pepper, L Pereira, K Perera, Y Perez, S Perez, P Perez Leguizamon, M Pernicka, R Perry, A Persico, Y Pesant, S Peska, D Peters, G Peters, L Pettigrew, T Phan, S Philippi, T Phinney, F Pico, A Pidal, B Piechowski-Jozwiak, A Pieroni, S Pineiro, V Piras, N Pizova, J Polanco, M Polin, A Polyakov, E Polychronopoulou, A Polymeris, D Popov, A Poppe, P Postorino, C Pozzerese, M Pradhan, L Prats, E Prazdnichkova, B Prendl, M Pretorius, P Profice, S Prokopenko, E Pudov, V Pujol Lereis, G Punzo Bravo, F Purroy, J Qiu, X Qu, V Quenardelle, H Quesada Garcia, L Radrizzani, A Radtke, T Raffelsberger, JM Ramirez Moreno, C Ramos-Estebanez, A Rani, P Rapantova, K Rashed, A Rasheed Nihara, J Rasmussen, L Redondo Robles, M Reif, P Reiner, P Rekova, A Renu, M Repetto, P Reyes, S Reyes Morales, JH Rha, J Ribeiro, S Ricci, C Richard, R Rigual, C Rinaldi, C Riveira Rodriguez, B Rizzato, TG Robinson, A Rocco, M Rodrigues, G Rodriguez, A Rodriguez Campello, F Rodriguez Lucci, M Rodriguez Yanez, C Roesler, C Roffe, R Roine, S Roine, A Roldan, F Romana Pezzella, M Romano, JS Roos, C Rosso, C Rostrup Kruuse, Y Roth, R Roukens, L Roveri, D Rozanski, J Rozniecki, C Rozsa, S Rudilosso, G Ruiz Ares, A Ruiz Franco, G Rum, J Ruuskanen, I Rybinnik, K Ryota, J Saarinen, V Saavedra, C Sabben, A Sabet, D Sagris, J Sahlas, N Sakai, P Salamanca, P Salgado, S Salig, T Salletmayr, M Salnikov, O Samoshkina, Y Samson, D Sanak, M Sànchez Cerón, P Santalucia, M Santamaria Cadavid, P Santiago, G Santo, B Sanz Cuesta, J Sargento, A Sarraj, K Sas, A Sas, O Satoshi, S Satsoglou, N Sattar, S Savitz, C Savopoulos, J Saw, M Sawicka, R Sawyer, T Scandura, N Schillinger, J Schindler, F Schlachetzki, I Schneider, R Schuppner, J Schurig, CJ Schwarzbach, M Sebejova, G Seidel, L Sekaran, D Selcuk, J Selvarajah, A Semerano, J Semjen, D Semushina, S Sen, M Seok Park, J Serena, O Serhat Tokgoz, W Serles, F Serrano, M Sevin, L Seynaeve, S Shah, N Shamalov, T Shang, M Sharma, A Sharrief, M Shazam Hussain, I Shchukin, W Shen, E Shepeleva, I Shinsuke, A Shmonin, A Shoamanesh, A Shuaib, A Shulga, G Sibolt, I Sibon, I Sicilia, M Siebert, E Sieczkowska, C Sila, AA Silva, D Silva, P Silva, Y Silva, M Silvestrini, Z Simony, A Simpkins, B Singh, D Sinha, I Sipos, O Skoda, P Skowron, M Skowronska, B Sliwinska, J Slonkova, A Smolkin, A Smyth, P Sobolewski, A Sobota, SI Sohn, M Soldatov, I Solganov, L Soloveva, E Solovyeva, N Sonntag, P Soors, M Sorgun, C Soriano, D Spence, K Spengos, L Sposato, G Staaf, K Stadler, L Stakhovskaya, K Stamatelopoulos, S Steinert, I Stetkarova, M Stiehm, R Stocker, J Stoinski, A Stoll, G Stotts, A Stumpp, P Sucapane, T Suenaga, X Sun, S Sundararajan, J Sung Kim, H Suzuki, N Svaneborg, G Szasz, W Szczuchniak, S Szczyrba, N Szegedi, A Szekely, Z Szewczyk, G Szilagyi, S Szlufik, K Szoboszlai, L Szpisjak, R Sztajzel, L Sztriha, SE Ta Wil, J Taggeselle, K Takamatsu, M Takao, W Taki, S Takizawa, M Talahma, A Tamayo, J Tan, D Tanne, A Tapanainen, T Tapiola, J Tarasiuk, T Tatlisumak, A Tayal, S Tcvetkova, P Teal, J Tejada Garcia, H Tejada Meza, D Tenora, M Terceno, A Terentiou, S Tezcan, D Thaler, A Thomson, E Thouvenot, M Tiainen, I Timberg, S Timsit, A Tinchon, D Tirschwell, C Togay Isikay, K Tokunaga, M Tolino, C Toloza, G Tomelleri, K Tomoyuki, LM Tomppo, Z Tong, L Tong, D Toni, J Torres, C Tossavainen, G Toth, A Tountopoulou, E Touze, M Tovar, K Toyoda, S Trillo, A Trommer, D Tropepi, D Tryambake, H Tu, S Tuetuencue, R Tumova, O Tumpula, G Turc, A Tutaj, J Tynkkynen, S Uchiyama, U Uchwat, L Uhrinyakova, R Ulku Acar, D Uluduz Ugurlu, X Urra, S Urui, M Usero Ruiz, D Vaclavik, K Vahedi, A Valikovics, J Valpas, P Van Acker, W Van Daele, G Vanderschueren, L Vanina Jure, R Varela, Z Varga, J Varvat, N Varvyanskaya, A Vasco Salgado, P Vasko, L Vass, S Vassilopoulou, I Vastagh, P Vazquez, L Vecsei, R Veltkamp, M Venti, M Verdugo, V Verocai, M Veronica Marroquin, C Veronica Simonsini, T Veverka, M Vigl, A Vila, C Vilar, JA Villanueva Osorio, J Virta, E Vitkova, B Voglsperger, J Volna, PA Von Weitzel-Mudersbach, N Vora, I Voznyuk, A Wach-Klink, A Wacongne, D Walters, Y Wang, J Wang, L Wang, X Wang, W Wang, N Wang, D Wang, H Wang, W Warnack, K Wartenberg, R Waters, M Waters, T Webb, J Weber, G Weiss, K Weissenborn, JI Weitz, B Weller, G Wen, G Weng, P Werner, D Werring, P Wester, W Whiteley, R Whiting, T Wijeratne, C Willems, L Wilson, C Wilson, T Winder, J Windt, A Winkler, A Winska-Tereszkiewicz, A Wisniewska, M Wittayer, A Wlodek, A Wojnarowska-Arendt, M Wolf, V Wolff, C Wolter, A Wong, H Wook Nah, H Worthmann, W Wu, S Wu, S Wunderlich, H Wurzinger, DG Wyse, B Xiao, W Xiaopeng, A Ximenez-Carrillo, L Xiong, Y Xiong, W Xiong, Y Xu, J Xu, Z Xu, B Yalo, T Yamada, M Yamasaki, L Yang, Y Yang, X Yang, Q Yang, B Yang, J Yang, I Yasuhiro, M Yee Lam, C Yegappan, S Yip, E Ylikallio, P Ylikotila, A Yongwon Jin, BW Yoon, Y Yoshida, L Yperzeele, H Yuan, H Yuasa, J Zalewska, C Zanferrari, E Zapata, D Zboznovits, I Zelenka, C Zhang, B Zhang, S Zhang, M Zhang, X Zhang, J Zhang, L Zhao, O Zhirnova, L Zhou, J Zielinska-Turek, I Zinchenko, M Ziomek, A Zitzmann, R Zweifler, J Zwiernik, Yperzeele, Laetitia, and NAVIGATE ESUS Investigators
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Male ,International Cooperation ,030204 cardiovascular system & hematology ,antiplatelet therapy ,law.invention ,Neurology (clinical) ,ischemic stroke ,anticoagulation ,Cohort Studies ,0302 clinical medicine ,Randomized controlled trial ,Rivaroxaban ,law ,Stroke ,education.field_of_study ,Aspirin ,Anticoagulant ,Settore BIO/14 ,Middle Aged ,3. Good health ,Treatment Outcome ,N/A ,Cardiology ,Platelet aggregation inhibitor ,Settore MED/26 - Neurologia ,Female ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,MEDLINE ,Population ,Foramen Ovale, Patent ,Subgroup analysis ,Article ,Statistics, Nonparametric ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,education ,Aged ,business.industry ,medicine.disease ,Human medicine ,business ,030217 neurology & neurosurgery ,Platelet Aggregation Inhibitors ,Factor Xa Inhibitors - Abstract
Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.
- Published
- 2018
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