BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. METHODS: This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. FINDINGS: 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94-1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02-1·21), but no significant differences in other safety endpoints. INTERPRETATION: The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost.
Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial / PERFORM Study, Investigators; Collaborators, ; Abdel Masih, Me; Ameriso, S; Barboza, A; Cirio, Jj; Crespo, E; Escaray, Ge; Esnaola, Mm; Estol, C; Ferrari, J; Fraiman, Hd; Garrote, M; Gatto, E; Giannaula, Rj; Gori, H; Herrera, G; Ioli, P; Losano, Jc; Povedano, G; Reich, E; Rey, Rc; Rotta Escalante, R; Saredo, G; Zurru, Mc; Anderson, C; Bladin, C; Crimmins, D; Davis, S; Donnan, G; Dunbabin, D; Frayne, J; Gates, P; Hankey, G; Helme, R; Herkes, G; Karrasch, J; Kimber, T; Jannes, J; Landau, P; Levi, C; Lueck, C; Markus, R; Phan, T; Schwartz, R; Schultz, D; Blacker, D; Read, S; Williams, M; Aichner, F; Auff, E; Bancher, C; Binder, H; Brainin, M; Brücke, T; Eggers, C; Fertl, E; Ladurner, G; Lalouschek, W; Lang, W; Mamoli, B; Mitrovic, N; Noisternig, G; Schmidt, R; Vosko, M; Willeit, J; Zaruba, E; Boon, P; Bourgeois, P; Caekebeke, J; Cals, N; Cras, P; Desfontaines, P; De Deyn, Pp; Dieudonne, L; De Klippel, N; Laloux, P; Maertens de Noordhout, A; Merlevede, K; Michotte, A; Pandolfo, M; Peeters, A; Peeters, D; Tack, P; Thijs, V; Van Buggenhout, E; Van Landegem, W; Vanhooren, G; Vermylen, P; Annes, M; Brondani, R; De Carvalho, Jj; Cendes, F; Fábio, Sr; Fernandes, Jg; Ferraz, Ac; De Freitas, Gr; Gagliardi, Rj; Gomes Neto, A; Haussen, Sr; Kowacs, Pa; Martins, Sc; Minelli, C; Moro, Ch; Noujaim, Je; Rocha, Ms; Da Silva, Mt; Silveira, Jr; Yamamoto, F; Zétola, Vh; Baldaranov, D; Deleva, N; Haralanov, L; Milanov, I; Mintchev, D; Petrova, N; Shotekov, P; Stamenov, B; Stamenova, P; Zahariev, Z; Arts, R; Bayer, N; Beaudry, M; Berger, L; Bozek, C; Collier, T; Cote, R; Desai, H; Durocher, A; Hachinski, V; Hill, M; Hoppe, B; Howse, D; Mackey, A; Maharaj, M; Minuk, J; Moddel, G; Novak, D; Penn, A; Rabinovitch, H; Selchen, D; Shuaib, A; Silva, J; Silver, F; Spence, D; Stotts, G; Tamayo, A; Teitelbaum, J; Veloso, F; Voll, C; Winder, T; Barrientos Uribe, N; Galdames Poblete, D; Garcia Figueroa, P; Gasic Yaconi, K; Jaramillo Muñoz, A; Lavados Germain, P; Lavados Montes, M; Prina Pacheco, L; Vargas Cañas, A; Venegas Francke, P; Chen, H; Cheng, Y; Cui, L; Di, Q; Dong, Q; Fan, D; Feng, H; Huang, Y; Li, J; Li, W; Li, Z; Lin, H; Liu, M; Miao, L; Ren, H; Wang, Y; Wu, J; Zhang, W; Zhao, G; Zhao, H; Zhou, H; Antoncic, I; Demarin, V; Lusic, I; Pavlicek, I; Poljakovic, Z; Soldo Butkovic, S; Bar, M; Bauer, J; Kalina, M; Kalita, Z; Kanovsky, P; Jura, R; Neumann, J; Rektor, I; Skoda, O; Vaclavik, D; Eerola, A; Hillbom, M; Kaste, M; Kinnunen, E; Koivisto, K; Numminen, H; Rissanen, A; Roine, R; Sivenius, J; Alamowitch, S; Amarenco, P; Autret, A; Avendano, S; Bataillard, M; Berthier, E; Besson, G; Bille Turc, F; Boulliat, J; Boulesteix, Jm; Brosset, C; Cesaro, P; Albucher, Jf; Clavelou, P; Colamarino, R; Crassard, I; de Broucker, T; de Bray, Jm; Desbordes, P; Diot, E; Ducrocq, X; Ellie, E; Faucheux, Jm; Giroud, M; Godefroy, O; Guillon, B; Huttin, B; Just, A; Lamy, C; Lejeune, P; Lucas, C; Macian Montoro, F; Mackowiak, A; Maillet Vioud, M; Pico, F; Milandre, L; Milhaud, D; Malbec, M; Moulin, T; Neau, Jp; Pinel, Jf; Robin, C; Rodier, G; Rosolacci, T; Rouanet, F; Rouhart, F; Sablot, D; Servan, J; Smadja, D; Trouillas, P; Valance, J; Viader, F; Viallet, F; Wolff, V; Zagnoli, F; Zuber, M; Angerer, M; Becker, U; Berlit, P; Berrouschot, J; Biniek, R; Bitsch, A; Brodhun, R; Dichgans, M; Diener, Hc; Druschky, Kf; Dux, R; Faiss, Jh; Ferbert, A; Gahn, G; Grotemeyer, Kh; Goertler, M; Grau, A; Griewing, B; Grond, M; Haan, J; Haberl, R; Hamann, G; Hamer, H; Harms, L; Heide, W; Hennerici, Mg; Henningsen, H; Hetzel, A; Hoff mann, F; Huber, R; Isenmann, S; Jander, S; Joerg, J; Kaps, M; Kastrup, A; Kessler, C; Koehler, W; Koelmel, Hw; Lichy, C; Luckner, K; Malessa, R; Mallmann, A; Meyding Lamadé, U; Molitor, H; Mueller Jensen, A; Muellges, W; Noth, J; Nueckel, M; Ochs, G; Poppert, H; Roether, J; Rosenkranz, M; Sander, D; Schaebitz, Wr; Schlachetzki, F; Schlegel, U; Schmid, E; Schneider, D; Schwarz, M; Seidel, G; Sieble, M; Sliwka, U; Stingele, R; Stoegbauer, F; Szabo, K; Töpper, R; Treib, J; Weissenborn, K; Widder, B; Witte, O; Karageorgiou, K; Mitsikostas, Dd; Papadimitriou, A; Papathanasopoulos, P; Vemmos, K; Chan, H; Ng, P; Tsoi, T; Wong, Lk; Bartos, L; Csanyi, A; Csiba, L; Csornai, M; Dioszeghy, P; Fazekas, A; Harcos, P; Horvath, S; Kaposzta, Z; Kerenyi, L; Kincses, J; Koves, A; Nikl, J; Panczel, G; Pongracz, E; Sebestyen, K; Semjen, J; Szabo, M; Szegedi, N; Valikovics, A; Varszegi, R; Vecsei, L; Borah, N; Ichaporia, N; Kaul, S; Meenakshi Sundaram, S; Mehndiratta, Mm; Misra, Uk; Murthy, Jm; Nayak, D; Poncha, F; Shah, A; Singh, G; Srinivasa, R; Venkateswarlu, K; Wadia, Rs; Collins, R; Harbison, J; Hickey, P; Kelly, P; Mccormack, P; Murphy, S; Adami, A; Agnelli, G; Agostoni, E; Anzola, Gp; Arnaboldi, M; Bassi, P; Billo, G; Bottacchi, E; Bovi, P; Cappa, S; Cappelletti, C; Carolei, A; Cavallini, A; Chiodo Grandi, F; Comi, G; Consoli, D; Corsi, Fm; Costanzo, E; De Falco, F; Devetag, F; Di Lazzaro, V; Di Piero, V; Diomedi, M; Fattorello Salimbeni, C; Federico, F; Feleppa, M; Ferrarese, C; Gandolfo, C; Giaccaglini, E; Giaquinto, S; Giobbe, D; Giometto, B; Greco, G; Guidetti, D; Guidotti, M; Iudice, A; Lembo, G; Marengo, C; Marini, P; Melis, M; Micieli, G; Musolino, R; Mutani, R; Neri, G; Parati, E; Pastore, L; Porazzi, D; Prati, P; Procaccianti, G; Rasura, M; Rossini, Pm; Santilli, Im; Semplicini, A; Silvestrini, Mauro; Tanganelli, P; Tedeschi, G; Tezzon, F; Tola, Mr; Villani, A; Zanferrari, C; Zarcone, D; Bickuviene, I; Budrys, V; Gumbrevicius, G; Obelieniene, D; Skaringa, Aa; Virketiene, I; Droste, D; Tan, Ks; Tharakan, J; Aleman Pedroza, Jm; Cantu Brito, C; Escamilla Garza, Jm; Fernandez Vera, Ja; Leal Cantu, R; Leon Flores, Li; Lopez Ruiz, M; Reyes Gutierrez, Ga; Reyes Morales, S; Rivera Castaño, L; Rodrigues Leyva, I; Ruiz Sandoval, Jl; Vega Boada, F; Belahsen, F; Kissani, N; Mosseddaq, R; Slassi, I; Yahyaoui, M; Boiten, J; Bornebroek, M; De Kort, Pl; De Leeuw, Hf; Donders, Rc; Franke, Cl; Hertzberger, Li; Jansen, Bp; Kappelle, Lj; Keizer, K; Koudstaal, Pj; Kuster, Ja; Limburg, M; Mulleners, Wm; Pop, Ph; Van Den Berg, Js; Van Gemert, Hm; Verbiest, Hb; Weinstein, Hc; Barber, A; Clark, M; Fink, J; Gommans, J; Jayathissa, S; Kilfoyle, D; Kumar, A; Hurtig, U; Indredavik, B; Kloster, R; Salvesen, R; Thomassen, L; Czlonkowska, A; Drozdowski, W; Fryze, W; Klimek, A; Kochanowski, J; Kozubski, W; Ksiazkiewicz, B; Kwiecinski, H; Kuczynska Zardzewialy, A; Motta, E; Nowacki, P; Nyka, W; Opala, G; Pierzchala, K; Pniewski, J; Podemski, R; Selmaj, K; Stelmasiak, Z; Stepien, A; Strzelecka Gorzynska, M; Szczudlik, A; Wajgt, A; Wiszniewska, M; Wlodek, A; Canhão, P; Correia, C; Cunha, L; Grilo Gonçalves, J; Machado Cândido, J; Salgado, Av; Bajenaru, O; Bulboaca, A; Campeanu, A; Lazar, T; Marginean, I; Minea, D; Pascu, I; Pereanu, M; Perju, L; Popescu, Cd; Simu, M; Stefanache, F; Toldisan, I; Tuta, S; Zaharia, C; Alifi rova, V; Arkhipov, S; Balunov, O; Balyazin, V; Belkin, A; Belova, A; Boiko, A; Bogdanov, E; Butko, D; Chukhlovina, M; Doronin, B; Ermilova, E; Evzelman, M; Fedin, A; Fedorova, N; Golikov, K; Golovkin, V; Gusev, E; Gustov, A; Jakupov, E; Kamchatnov, P; Khabirov, F; Kirienko, A; Klimov, I; Klocheva, E; Kotov, S; Kuznetsov, A; Laskov, V; Levin, Y; Mashkova, N; Nazarov, A; Novikova, L; Odinak, M; Parfenov, V; Pilipenko, P; Pokrovsky, A; Poverennova, I; Rodoman, G; Roshkovskaya, L; Shirokov, E; Shmyriov, V; Sholomov, I; Skoromets, A; Skvortsova, V; Spirin, N; Stakhovskaya, L; Sharov, M; Sherman, M; Shutov, A; Strachunskaya, E; Stulin, I; Suslina, Z; Volosevitch, A; Vorobiev, P; Vorobyeva, O; Voronkova, L; Voskresenskaya, O; Zhuliov, N; Chan, B; Chang, Hm; Ramani, Nv; Brozman, M; Dvorak, M; Dzugan, J; Garay, R; Gdovinova, Z; Gurcik, L; Krastev, G; Kukumberg, P; Kurca, E; Lisy, L; Meluch, S; Nyeky, M; Turcani, P; Vyletelka, J; Klanjscek, G; Zujovic, E; Zupan, M; Zvan, B; Bester, Fc; Carr, J; Coetzee, C; Frost, Ac; Gardiner, J; Giampaolo, Dl; Kesler, S; Lurie, Dm; Retief, Cf; Roos, Js; Bae, Hj; Cha, Jk; Cho, Kh; Heo, Jh; Kim, Eg; Kim, Js; Lee, Bc; Lee, Kh; Lee, J; Rha, Jh; Yoon, Bw; Alvarez Sabin, J; Arboix Damunt, A; De Arce Borda, A; Asensi Alvarez, Jm; Bermejo Pareja, F; Botia Paniagua, E; Casado Naranjo, I; Castillo Sanchez, J; Chamorro Sanchez, A; Davalos Errando, A; Diaz Marin, C; Diez Tejedor, E; Egido Herrero, Ja; Fernandez Bolaños, R; Fernandez Fernandez, O; Figuerola Roig, A; Sclarsky, Dg; Gil Nuñez, A; Gomez Sanchez, Jc; Gomez, Ci; Escobar, E; Gonzalez Masegosa, A; Gonzalez Menacho, J; Gracia Fleta, F; Izquierdo Ayuso, G; Jimenez Hernandez, D; Jimenez Martinez, C; Lago Martin, A; Lainez Andres, Jm; Larracoechea Jausoro, J; López Fernández, Jc; Maestre Moreno, J; Marti Vilalta, Jl; Martin Gonzalez, R; Masjuan Vallejo, J; Medina Rodriguez, A; Moltó Jorda, Jm; Moreno Carretero, Mj; Moris de le Tassa, G; Morlan Gracia, L; Mostacero Miguez, E; Osuna Pulido, T; Pareja Martinez, A; Pinedo Brochado, A; Pons Amate, Jm; Rodriguez Alvarez, Jr; Roquer Gonzalez, J; Sanahuja Montesinos, J; Sanchez Sanchez, Mc; Segura Martin, T; Serena Leal, J; Tejada García, J; Trejo Gabriel, Jm; Vivancos Mora, J; Andersson, B; Bysell, Se; Cederin, B; Laska, Ac; Lindgren, A; Petersson, J; Wahlgren, Ng; Wallén, T; Baumgartner, R; Beer, Hj; Hirt, L; Hungerbuehler, H; Lyrer, P; Mattle, Hp; Michel, P; Mueller, F; Tettenborn, B; Chang, Kc; Jeng, Js; Lien, Lm; Lin, Rt; Liu, Ch; Liu, Sj; Po, H; Wu, Sl; Chankrachang, S; Laptikultham, S; Nidhinandana, S; Pongpakdee, S; Poungvarin, N; Suwanwela, Nc; Tiamkao, S; Towanabut, S; Benammou, S; Frih Ayed, M; Gouider, R; Hentati, F; Mhiri, C; M'Rabet, A; Mrissa, R; Bahar, S; Balkan, S; Can, U; Dalkara, T; Kirbas, D; Kumral, E; Ozdemir, G; Ozeren, A; Ozmenoglu, M; Ozturk, S; Bamford, J; Barber, M; Barer, D; Baron, Jc; Bath, P; Broughton, D; Brown, M; Chataway, J; Curless, R; Darawil, K; Datta, P; Dennis, M; Durairaj, R; Egbuji, J; Ellis, S; Ford, G; Freeman, A; Fulcher, R; Gray, C; Harrington, F; Hudson, C; Iveson, E; James, M; Jenkinson, D; Kalra, L; Kelly, D; Krishnamoorthy, S; Langhorne, P; Lees, K; Magorrian, M; Macleod, M; Macleod, Mj; Macwalter, R; Markus, H; Muhiddin, K; Muir, K; Murphy, P; Power, M; Price, C; Rashed, K; Robinson, T; Rudd, A; Sanmuganathan, P; Sharma, J; Shaw, L; Shetty, H; Smithard, D; Tyrrell, P; Vahidassr, Md; Venables, G; Watt, M; White, R; Lebedynets, V; Maly, V; Mischenko, T; Moskovko, S; Orzheshkovskyy, V; Smolanka, V; Yavors'Ka, V; Zozulya, I.. - In: THE LANCET. - ISSN 0140-6736. - STAMPA. - 377:(2011), pp. 2013-2022. [10.1016/S0140-6736(11)60600-4]
Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial.
SILVESTRINI, Mauro;
2011-01-01
Abstract
BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. METHODS: This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. FINDINGS: 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94-1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02-1·21), but no significant differences in other safety endpoints. INTERPRETATION: The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
