202 results on '"Easton, Jd"'
Search Results
2. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source
- Author
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Diener, Hc, Sacco, Rl, Easton, Jd, Granger, Cb, Bernstein, Ra, Uchiyama, S, Kreuzer, J, Cronin, L, Cotton, D, Grauer, C, Brueckmann, M, Chernyatina, M, Donnan, G, Ferro, Jm, Grand, M, Kallmunzer, B, Krupinski, J, Lee, Bc, Lemmens, R, Masjuan, J, Odinak, M, Saver, Jl, Schellinger, Pd, Toni, D, Toyoda, K, RE-SPECT ESUS Steering Committee and Investigators, Tassi, R, Cardiology, and ACS - Heart failure & arrhythmias more...
- Subjects
Male ,Stroke/etiology ,medicine.medical_specialty ,Aged ,Antithrombins ,Aspirin ,Dabigatran ,Double-Blind Method ,Female ,Hemorrhage ,Humans ,Incidence ,Intracranial Embolism ,Kaplan-Meier Estimate ,Middle Aged ,Platelet Aggregation Inhibitors ,Recurrence ,Secondary Prevention ,Stroke ,Medizin ,030204 cardiovascular system & hematology ,Antithrombins/administration & dosage ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Hemorrhage/chemically induced ,Intracranial Embolism/drug therapy ,medicine ,Dabigatran/administration & dosage ,030212 general & internal medicine ,Aspirin/administration & dosage ,Platelet Aggregation Inhibitors/administration & dosage ,Rivaroxaban ,business.industry ,Hazard ratio ,Warfarin ,Atrial fibrillation ,General Medicine ,medicine.disease ,Platelet aggregation inhibitor ,business ,medicine.drug - Abstract
BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.). more...
- Published
- 2019
Catalog
3. Antithrombotic Treatment of Embolic Stroke of Undetermined Source RE-SPECT ESUS Elderly and Renally Impaired Subgroups
- Author
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Diener, H-C, Sacco, RL, Easton, JD, Granger, CB, Bar, M, Bernstein, RA, Brainin, M, Brueckmann, M, Cronin, L, Donnan, G, Gdovinova, Z, Grauer, C, Kleine, E, Kleinig, TJ, Lyrer, P, Martins, S, Meyerhoff, J, Milling, T, Pfeilschifter, W, Poli, S, Reif, M, Rose, DZ, Sanak, D, Schaebitz, W-R, Diener, H-C, Sacco, RL, Easton, JD, Granger, CB, Bar, M, Bernstein, RA, Brainin, M, Brueckmann, M, Cronin, L, Donnan, G, Gdovinova, Z, Grauer, C, Kleine, E, Kleinig, TJ, Lyrer, P, Martins, S, Meyerhoff, J, Milling, T, Pfeilschifter, W, Poli, S, Reif, M, Rose, DZ, Sanak, D, and Schaebitz, W-R more...
- Abstract
Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-genera more...
- Published
- 2020
4. Edoxaban versus warfarin in patients with atrial fibrillation
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Robert P. Giugliano, Christian T. Ruff, Eugene Braunwald, Sabina A. Murphy, Stephen D. Wiviott, Jonathan L. Halperin, Albert L. Waldo, Michael D. Ezekowitz, Jeffrey I. Weitz, Jind?ich ?pinar, Witold Ruzyllo, Mikhail Ruda, Yukihiro Koretsune, Joshua Betcher, Minggao Shi, Laura T. Grip, Shirali P. Patel, Indravadan Patel, James J. Hanyok, Michele Mercuri, Elliott M. Antman, Braunwald E, Antman EM, Giugliano RP, Ruff CT, Morin SE, Hoffman EB, Murphy SA, Deenadayalu N, Grip L, Mercuri M, Lanz H, Patel I, Curt V, Duggal A, Hanyok J, Davé J, Morgan D, Choi Y, Shi M, Jin J, Xie J, Crerand W, Kappelhof J, Maxwell W, Skinner M, Patel S, Betcher J, Selicato G, Otto C. Jr, Reissner C, Smith K, Ostroske J, Ron A, Giugliano R, Connolly S, Camm J, Ezekowitz M, Halperin J, Waldo A, Paolasso E, Aylward P, Heidbuchel H, Nicolau JC, Goudev A, Roy D, Weitz J, Corbalán R, Yang Y, Botero R, Bergovec M, Ŝpinar J, Grande P, Hassager C, Voitk J, Huikuri H, Nieminen M, Blanc JJ, LeHeuzey JY, Mitrovic V, Alexopoulos D, Sotomora G, Kiss R, SomaRaju B, Lewis B, Merlini P, Metra M, Koretsune Y, Yamashita T, García Castillo A, Ophuis T, White H, Atar D, Horna M, Babilonia N, Ruzyllo W, Morais J, Dorobantu M, Ruda M, Ostojic M, Duris T, Dalby A, Chung N, Zamorano JL, Juul Möller S, Moccetti T, Chen SA, Sritara P, Oto A, Parkhomenko A, Senior R, Verheugt F, Skene A, Anderson J, Bauer K, Easton JD, Goto S, Wiviott S, Lowe C, Awtry E, Berger CJ, Croce K, Desai A, Gelfand E, Goessling W, Greenberger NJ, Ho C, Leeman DE, Link MS, Norden AD, Pande A, Rost N, Ruberg F, Silverman S, Singhal A, Vita JA, Vogelmann O, Gonzalez C, Ahuad Guerrero R, Rodriguez M, Albisu J, Rosales E, Allall O, Reguero M, Alvarez C, Garcia M, Ameriso S, Ameriso P, Amuchastegui M, Caceres M, Beloscar J, Petrucci J, Berli M, Budassi N, Valle M, Bustamante Labarta G, Saravia M, Caccavo A, Fracaro V, Cartasegna L, Novas V, Caruso O, Zarandon RS, Colombo H, Morandini M, Cuello J, Rosell M, Cuneo C, Bocanera M, D'Amico A, Cendali G, Dran R, Moreno V, Estol C, Davolos M, Facello A, Facello M, Falu E, Iriarte M, Femenia F, Arrieta M, Fuselli J, Zanotti A, Gant Lopez J, Meiller F, Garcia Duran R, Perlo D, Garrido M, Ceirano C, Giacomi G, Eden M, Giannaula R, Huerta M, Goicoechea R, von Wulffen M, Hominal M, Bianchini M, Jure H, Jure D, Kevorkian R, Monaco F, Lanternier G, Belcuore M, Liniado G, Iglesias M, Litvak B, Nigro A, Llanos J, Vignau S, Lorente C, Shatsky K, Lotti J, Raimondi G, Mackinnon I, Carne M, Manuale O, Calderon M, Marino J, Funes I, Muntaner J, Gandur H, Nul D, Verdini E, Piskorz D, Tommasi A, Povedano G, Casares E, Pozzer D, Fernandez E, Prado A, Venturini C, Ramos H, Navarrete S, Alvarez M, Sanchez A, Bowen L, Sanjurjo M, Codutti O, Saravia Toledo S, Formoso I, Schmidberg J, Goloboulicz A, Schygiel P, Buzzetti C, Severino P, Morara P, Sosa Liprandi M, Teves M, Vico M, Morell Y, Anderson C, Paraskevaidis T, Arstall M, Hoffmann B, Colquhoun D, Price Smith S, Crimmins D, Slattery A, Dart A, Kay S, Davis S, Silver G, Flecknoe Brown S, Roberts J, Gates P, Jones S, Lehman R, Morrison H, McKeirnan M, Li J, Paul V, Batta C, Purnell P, Perrett L, Szto G, O'Shea V, Capiau L, Banaeian F, De Bleecker J, de Koning K, De Tollenaere M, De Bruyne L, Desfontaines P, Tincani G, Meeusen K, Herzet J, Malmendier D, Mairesse G, Raepers M, Parqué J, Clinckemaille N, Scavée C, Huyberechts D, Stockman D, Jacobs C, Vandekerckhove Y, Derycker K, Vanwelden J, van Welden J, Vervoort G, Mestdagh I, Vrolix M, Beerts C, Wollaert B, Denie D, Amato Vincenzo de Paola A, Coutinho E, Andrade Lotufo P, de Melo RF, Atie J, Motta C, Augusto Alves da Costa F, Ferraz RF, Bertolim Precoma D, Sehnem E, Botelho R, Cunha S, Brondani R, Fleck N, Chaves Junior H, Silva J, Costantini C, Barroso D, De Patta M, Pereira V, Duda N, Laimer R, Dutra O, Morgado S, Faustino Saporito W, Seroqui M, Ferreira L, Araújo E, Finimundi H, Daitz C, Gagliardi R, Pereira G, Gomes M, Gomes A, Guimarães A, Ninho L, Jaeger C, Pereira L, Jorge J, Cury C, Kaiser S, Almeida A, Kalil C, Radaelli G, Kunz Sebba Barroso de Souza W, Morales K, Leaes P, Luiz RO, Pimenta Almeida J, Gozalo A, Reis G, Avellar K, Reis Katz Weiand L, Leipelt J, Rocha J, Barros R, Rodrigues L, Rocha MR, Rodrigues A, Rodrigues D, Rossi dos Santos F, Pagnan LG, Sampaio R, do Val R, Saraiva J, Vicente C, Simoes M, Carraro A, Sobral Filho D, Lustosa E, Villas Boas F, Almeida M, Zimmermann S, Zimmermann EB, Chompalova B, Parishev G, Denchev S, Milcheva N, Donova T, Gergova V, Georgiev B, Kostova E, Kinova E, Hergeldjieva V, Kamenova P, Manolova A, Vasilev I, Mihov A, Miteva B, Mincheva V, Stoyanovski V, Nikolov F, Vasilev D, Pencheva G, Kostov K, Petranov S, Milusheva T, Popov A, Staneva A, Momchilova Lozeva D, Todorov G, Nyagina M, Tumbev H, Tumbeva D, Tzekova M, Kitova M, Manoylov E, Archibald J, Antle S, Bhargava R, Stafford C, Bose S, Hundseth M, Cha J, Otis J, Chehayeb R, Lepage C, Chilvers M, Vansickle L, Cleveland D, Valley S, Constance C, Gauthier M, Costi P, Masson C, Coutu B, Denis I, du Preez M, Kubanska A, Dufresne M, Krider J, Eikelboom J, Zondag M, Fortin C, Viau C, Green M, Houbraken D, Hatheway R, Mabee J, Heath J, Scott L, Ho K, Ho V, Hoag G, Standring R, Huynh T, Perkins L, Kouz S, Roy M, Labonte R, Dewar C, Lainesse A, St Germain L, Lam S, Lam H, Lichtenstein T, Roberts P, Luton R, Douglas S, Ma P, Seib M, MacCallum C, Matthews J, Malette P, Vaillancourt T, Maranda C, Studenikow E, Mawji A, Morely A, Morrison D, Roth M, Mucha M, Najarali A, Lamoureux U, Nicholson R, O'Hara G, Banville P, O'Mahony W, Bolton R, Parkash R, Carroll L, Pesant Y, Sardin V, Polasek P, Turri L, Qureshi A, Nethercott C, Ricci J, Bozek B, Rupka D, Marchand C, Shu D, Silverio G, St Hilaire R, Morissette A, Sussman J, Kailey P, Syan G, Bobbie C, Talajic M, David D, Talbot P, Tremblay M, Teitelbaum I, Teitelbaum J, Velthuysen G, Giesbrecht L, Wahby R, Morley A, Wharton S, Caterini T, Woodford T, Balboa W, Matus LR, Bugueño C, Mondaca PM, Cobos J, Obreque C, Corbalan R, Parada A, Florenzano F, Diaz PA, Lopetegui M, Rebolledo C, Manriquez L, Silva LM, Martinez D, Llamas RR, Opazo M, Pérez MC, Pincetti C, Carrasco GT, Potthoff S, Staub JZ, Campisto Y, Stockins B, Lara CL, Yovaniniz P, Azua MG, Bai F, Xu GL, Chen JZ, Xie XD, Chen XP, Zhang X, Dong YG, Feng C, Fu GS, Zhang P, Hong K, You ZG, Hong L, Qiu Y, Jiang XJ, Qu Z, Li L, Liu H, Li TF, Kong YQ, Li WM, Liu B, Li ZQ, Liu Y, Liao DN, Gu XJ, Liu L, Lu ZH, Ma SM, Yang ZY, Wang DM, Qi SY, Wang GP, Shi XJ, Wei M, Huang D, Wu SL, Li YE, Xu JH, Gu JY, Xu YM, Liang YZ, Yang K, Li AY, Yang YJ, Zheng X, Zheng Y, Gao M, Yin YH, Xu YP, Yu B, Li LL, Yuan ZY, Qiang H, Zhang HQ, Lin YN, Zhang Z, Kang H, Zhao RP, Han RJ, Zhao XL, Wang JQ, Zheng ZQ, Li BG, Zhou SX, Zhang YL, Accini J, Accini M, Cano N, Pineda LL, Delgado Restrepo J, Arroyave C, Fernández Ruiz R, Diaz IA, Hernandez H, Delgado P, Jaramillo Muñoz C, Builes A, Manzur F, Rodriguez ER, Moncada Corredor M, Giraldo DL, Orozco Linares L, Fonseca J, Quintero A, Gonzales C, Sanchez Vallejo G, Mejia IP, Bagatin J, Carevic V, Car S, Jeric M, Ciglenecki N, Tusek S, Ferri Certic J, Romic I, Francetic I, Ausperger KM, Jelic V, Jurinjak SJ, Knezevic A, Buksa B, Samardzic P, Lukenda KC, Steiner R, Kirner D, Sutalo K, Bakliza Z, Vrazic H, Lucijanic T, Bar M, Brodova P, Berka L, Kunkelova V, Brtko M, Burianova H, Cermak O, Elbl L, Ferkl R, Florian J, Francek L, Golan L, Gregor P, Honkova M, Hubac J, Jandik J, Jarkovsky P, Jelinek Z, Jerabek O, Jirmar R, Kobza R, Kochrt M, Kostkova G, Kosek Z, Kovar P, Kuchar R, Kvasnicka J, Ludka O, Machova V, Krocova E, Melichar M, Nechanicky R, Olsr J, Peterka K, Petrova I, Havlova I, Pisova J, Podrazil P, Jirsova E, Reichert P, Slaby J, Spacek R, Spinar J, Labrova R, Vodnansky P, Samkova D, Zidkova E, Dodt K, Christensen H, Christensen L, Loof A, Ibsen H, Madsen H, Iversen H, Veng Olsen T, Nielsen H, Olsen R, Overgaard K, Petrovic V, Raymond I, Raae D, Sand N, Svenningsen A, Torp Pedersen C, Jakobsen U, Wiggers H, Serup Hansen K, Kaik J, Stern A, Kolk R, Laane E, Rivis L, Paumets M, Laheäär M, Rosenthal A, Rajasalu R, Vahula V, Ratnik E, Kaarleenkaski S, Hussi E, Valpas S, Jäkälä P, Lappalainen T, Mäenpää A, Viitaniemi J, Nyman K, Sankari T, Rasi H, Salminen O, Virtanen V, Nappila H, Le Heuzey J, Agraou B, El Jarroudi F, Amarenco P, Boursin P, Babuty D, Boyer M, Belhassane A, Berbari H, Blanc J, Dias P, Coisne D, Berger N, Decoulx E, El Jarroudi M, Dinanian S, Arfaoui M, Hermida J, Deruche E, Kacet S, Corbut S, Poulard J, Leparree S, Roudaut R, Duprat C, Al Zoebi A, Wurow A, Bernhardt P, Dichristin U, Berrouschot J, Vierbeck S, Beyer 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Reddy J, Banker D, Sheth T, Benjarge P, Surushe S, Bharani A, Solanki R, Bhargava V, Rathi A, Biniwale A, Bhuti M, Calambur N, Somaraju B, Karnwal N, Chopda M, Mali N, Goyal N, Saini A, Gupta J, Singh P, Hadan S, Savanth P, Hardas S, Thakor G, Hiremath J, Ghume A, Jain R, Pahuja M, Joseph S, Oommen D, Joseph J, Thomas R, Joshi H, Iby, Kale V, Raut N, Kandekar B, Kandekar S, Kishore R, Krishnan H, Kotiwale V, Kulkarni R, Deokar M, Kulkarni G, Lawande A, Kumar P, Karpuram M, Kumar A, Francis J, Kumbla M, Anthony A, Lavhe P, Kale M, Mardikar H, Bhaskarwar P, Mathur A, Sharma P, Menon J, Francis V, Namjoshi D, Shelke S, Narendra J, Natarajan S, Oomaan A, Gurusamy P, Angel J, Purayil MP, Shams S, Pandurangi U, Sababathi R, Parekh P, Jasani B, Patki N, Babbar A, Pinto B, Kharalkar H, Premchand R, Jambula H, Rao M, Vuriya A, Ravi Shankar A, Reddy R, Bekal S, Barai A, Saha D, Gadepalli R, Sant H, Jadhav D, Sarna M, Arora T, Sawhney J, Singh R, Sethi K, Bansal N, Sethia A, Sethia S, Shetty G, Sudheer R, Singh G, Gupta R, Srinivas A, Thankaraj L, Varma S, Kaur A, Vinod MV, Thakur B, Zanwar I, Dharmarao A, Atar S, Lasri E, Dicker D, Marcoviciu D, Elias M, Ron GA, Francis A, Ghantous R, Goldhaber A, Goldhaber M, Gottlieb S, Rouwaida S, Grossman E, Dagan T, Hasin Y, Roshrosh M, Hayek T, Majdoub A, Klainman E, Genin I, Lahav M, Gilat T, Ben Ari M, Lishner M, Karny M, Ouzan E, Givoni H, Rozenman Y, Logvinenko S, Schiff E, Sterlin J, Shochat M, Aloni I, Swissa M, Belatsky V, Tsalihin D, Kisos D, Zeltser D, Platner N, Berni A, Giovannelli F, Boriani G, Cervi E, Comi G, Peruzzotti L, Cuccia C, Forgione C, De Caterina R, De Pace D, De Servi S, Mariani M, Di Lenarda A, Mazzone C, Di Pasquale G, Di Niro M, Fattore L, Bosco B, Grassia V, Murena E, Laffi, Gaggioli G, Lo Pinto G, Raggi F, Marino P, Francalacci G, Babbolin M, Bulgari M, Penco M, Lioy E, Marciano C, Pirelli S, Paradiso G, Piseddu G, Fenu L, Raisaro A, Granzow K, Rasura M, Cannoni S, Severi S, Breschi M, Toschi V, Gagliano 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McLaurin B, Lack A, Mega J, Marti J, Meholick A, Skinner J, Mehrle A, Wall J, Mendelson R, Cervellione K, Mercado A, Cajulis C, Michlin B, Romero Colon J, Milas J, Sanders D, Miller R, Sanchez S, Miller S, Gryczan J, Mody F, Strugatsky S, Moran J, Garner S, Morledge J, Bowman B, Mouhaffel A, Parrott N, Mounsey P, Schuler C, Mowdy M, Todd S, Mullen P, Raziano S, Murphy A, Oehmann V, Nadar V, Parker A, Naidu J, West M, Nallasivan M, Goza J, Nguyen T, Nomanee S, Nielsen R, Wilmot M, Oberoi M, Thakkar N, Oppenheimer K, McCormick J, Orchard R, Garcia L, Osborne J, Gonzalez M, Oza S, Joseph L, Patnam S, Dennison K, Pavon H, Gorry N, Pearlstein R, Montayne S, Pentz W, Duncan D, Peters P, Chacon L, Petruzziello F, Morlando F, Pettis K, Brown F, Pezzella S, Kirk D, Poulathas A, Cush S, Pratt R, Neeper L, Pribble A, Lowe K, Pudi K, Sham L, Pugeda J, Ebert J, Quadrel M, Rafla E, Quinlan E, Reed C, Quinn J, Hemmen C, Rama P, Domingo D, Redondo V, Wroblewski J, Renzi M, Stanley E, Richwine R, Pazier P, Riofrio K, Braun D, Robinson J, Cherrico M, Roehll W, Hollihan P, Rosado, Barnhorst M, Rosado J, Bamhorst M, Rosen R, Martin C, Ross S, Freeman R, Ruoff G, Nelson T, Sacco J, Ball E, Samal A, Schomburg J, Sandberg J, Lafave J, Savin V, Clifton R, Schaefer S, Fekete A, Schneider R, Schneider W, Schulman D, Mercer S, Seals A, Ullig T, Holt A, Seide H, Mather N, Shah G, Witt P, Shalaby A, Seese M, Shanes J, Fleets J, Shaoulian E, Hren A, Sheikh K, Hengerer T, Shih H, Browning J, Shoukfeh M, Stephenson L, Siler T, Champagne M, Simpson P, Meyer R, Singh N, Turner K, Singh V, Nelson M, Skierka R, Hughes B, Keene R, Smith R, Hodnett P, Spangenthal S, Thomason L, Sperling M, Vasquez E, Spivack E, McCartney P, Staniloae C, Liu M, Steljes A, Cox C, Struble R, Vittitow T, Suresh D, Frost J, Swerchowsky V, Freemyer D, Szulawski I, Herwehe S, Tahirkheli N, Springer K, Takata T, Bruton T, Talano J, Leo L, Tami L, Corchado D, Tatarko M, Swauger M, Tawney K, Dastoli K, Teague S, Young K, Tee H, Mitchell T, Teixeira J, Southam D, Torres M, Tucker P, Salas L, Updegrove J, Hanna K, Val Mejias J, Harrelson KG, Vemireddy D, Cardoza T, Verma S, Parsons T, Vicari R, Warren K, Vijay N, Washam M, Vossler M, Kilcup S, Walsh R, Renaud K, Ward S, Locklear T, Waxman F, Sanchez G, Weiss R, St Laurent B, Westcott J, Williams D, Gibson C, Williams R, Dowling C, Willis J, VonGerichten S, Wood K, Capasso Gulve E, Worley S, Pointer S, Yarows S, Sheehan T, Yasin M, Yi J, Dongas B, Yousuf K, Zakhary B, Curtis S, Zeig S, Mason T, Zellner C, Harden M, Roper E, Waseem M, Grammer M., PERRONE FILARDI, PASQUALE, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai [New York] (MSSM), University Hospitals Case Medical Center (CLEVELAND - UHCMC), University Hospitals Case Medical Center, Jefferson Medical College (JMC), Thomas Jefferson University Hospitals, Thrombosis and Atherosclerosis Research Institute (TARI), McMaster University [Hamilton, Ontario], University Hospital Brno, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Cardiology Research Center (MOSCOU - CRC), Cardiology Research Center, National Hopital Organization (OSAKA - NHO), Osaka National Hospital, Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Graduate School, Endocrinology, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Nursing, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, General Internal Medicine, Giugliano, Rp, Ruff, Ct, Braunwald, E, Murphy, Sa, Wiviott, Sd, Halperin, Jl, Waldo, Al, Ezekowitz, Md, Weitz, Ji, Špinar, J, Ruzyllo, W, Ruda, M, Koretsune, Y, Betcher, J, Shi, M, Grip, Lt, Patel, Sp, Patel, I, Hanyok, Jj, Mercuri, M, Antman, Em, Comi, Giancarlo, ENGAGE AF TIMI 48, Investigators, Robert P., Giugliano, Christian T., Ruff, Eugene, Braunwald, Sabina A., Murphy, Stephen D., Wiviott, Jonathan L., Halperin, Albert L., Waldo, Michael D., Ezekowitz, Jeffrey I., Weitz, Jind?ich, ?pinar, Witold, Ruzyllo, Mikhail, Ruda, Yukihiro, Koretsune, Joshua, Betcher, Minggao, Shi, Laura T., Grip, Shirali P., Patel, Indravadan, Patel, James J., Hanyok, Michele, Mercuri, Elliott M., Antman, Morin, Se, Hoffman, Eb, Deenadayalu, N, Grip, L, Lanz, H, Curt, V, Duggal, A, Hanyok, J, Davé, J, Morgan, D, Choi, Y, Jin, J, Xie, J, Crerand, W, Kappelhof, J, Maxwell, W, Skinner, M, Patel, S, Selicato, G, Otto C., Jr, Reissner, C, Smith, K, Ostroske, J, Ron, A, Giugliano, R, Connolly, S, Camm, J, Ezekowitz, M, Halperin, J, Waldo, A, Paolasso, E, Aylward, P, Heidbuchel, H, Nicolau, Jc, Goudev, A, Roy, D, Weitz, J, Corbalán, R, Yang, Y, Botero, R, Bergovec, M, Ŝpinar, J, Grande, P, Hassager, C, Voitk, J, Huikuri, H, Nieminen, M, Blanc, Jj, Leheuzey, Jy, Mitrovic, V, Alexopoulos, D, Sotomora, G, Kiss, R, Somaraju, B, Lewis, B, Merlini, P, Metra, M, Yamashita, T, García Castillo, A, Ophuis, T, White, H, Atar, D, Horna, M, Babilonia, N, Morais, J, Dorobantu, M, Ostojic, M, Duris, T, Dalby, A, Chung, N, Zamorano, Jl, Juul Möller, S, Moccetti, T, Chen, Sa, Sritara, P, Oto, A, Parkhomenko, A, Senior, R, Verheugt, F, Skene, A, Anderson, J, Bauer, K, Easton, Jd, Goto, S, Wiviott, S, Lowe, C, Awtry, E, Berger, Cj, Croce, K, Desai, A, Gelfand, E, Goessling, W, Greenberger, Nj, Ho, C, Leeman, De, Link, M, Norden, Ad, Pande, A, Rost, N, Ruberg, F, Silverman, S, Singhal, A, Vita, Ja, Vogelmann, O, Gonzalez, C, Ahuad Guerrero, R, Rodriguez, M, Albisu, J, Rosales, E, Allall, O, Reguero, M, Alvarez, C, Garcia, M, Ameriso, S, Ameriso, P, Amuchastegui, M, Caceres, M, Beloscar, J, Petrucci, J, Berli, M, Budassi, N, Valle, M, Bustamante Labarta, G, Saravia, M, Caccavo, A, Fracaro, V, Cartasegna, L, Novas, V, Caruso, O, Zarandon, R, Colombo, H, Morandini, M, Cuello, J, Rosell, M, Cuneo, C, Bocanera, M, D'Amico, A, Cendali, G, Dran, R, Moreno, V, Estol, C, Davolos, M, Facello, A, Facello, M, Falu, E, Iriarte, M, Femenia, F, Arrieta, M, Fuselli, J, Zanotti, A, Gant Lopez, J, Meiller, F, Garcia Duran, R, Perlo, D, Garrido, M, Ceirano, C, Giacomi, G, Eden, M, Giannaula, R, Huerta, M, Goicoechea, R, von Wulffen, M, Hominal, M, Bianchini, M, Jure, H, Jure, D, Kevorkian, R, Monaco, F, Lanternier, G, Belcuore, M, Liniado, G, Iglesias, M, Litvak, B, Nigro, A, Llanos, J, Vignau, S, Lorente, C, Shatsky, K, Lotti, J, Raimondi, G, Mackinnon, I, Carne, M, Manuale, O, Calderon, M, Marino, J, Funes, I, Muntaner, J, Gandur, H, Nul, D, Verdini, E, Piskorz, D, Tommasi, A, Povedano, G, Casares, E, Pozzer, D, Fernandez, E, Prado, A, Venturini, C, Ramos, H, Navarrete, S, Alvarez, M, Sanchez, A, Bowen, L, Sanjurjo, M, Codutti, O, Saravia Toledo, S, Formoso, I, Schmidberg, J, Goloboulicz, A, Schygiel, P, Buzzetti, C, Severino, P, Morara, P, Sosa Liprandi, M, Teves, M, Vico, M, Morell, Y, Anderson, C, Paraskevaidis, T, Arstall, M, Hoffmann, B, Colquhoun, D, Price Smith, S, Crimmins, D, Slattery, A, Dart, A, Kay, S, Davis, S, Silver, G, Flecknoe Brown, S, Roberts, J, Gates, P, Jones, S, Lehman, R, Morrison, H, Mckeirnan, M, Li, J, Paul, V, Batta, C, Purnell, P, Perrett, L, Szto, G, O'Shea, V, Capiau, L, Banaeian, F, De Bleecker, J, de Koning, K, De Tollenaere, M, De Bruyne, L, Desfontaines, P, Tincani, G, Meeusen, K, Herzet, J, Malmendier, D, Mairesse, G, Raepers, M, Parqué, J, Clinckemaille, N, Scavée, C, Huyberechts, D, Stockman, D, Jacobs, C, Vandekerckhove, Y, Derycker, K, Vanwelden, J, van Welden, J, Vervoort, G, Mestdagh, I, Vrolix, M, Beerts, C, Wollaert, B, Denie, D, Amato Vincenzo de Paola, A, Coutinho, E, Andrade Lotufo, P, de Melo, Rf, Atie, J, Motta, C, Augusto Alves da Costa, F, Ferraz, Rf, Bertolim Precoma, D, Sehnem, E, Botelho, R, Cunha, S, Brondani, R, Fleck, N, Chaves Junior, H, Silva, J, Costantini, C, Barroso, D, De Patta, M, Pereira, V, Duda, N, Laimer, R, Dutra, O, Morgado, S, Faustino Saporito, W, Seroqui, M, Ferreira, L, Araújo, E, Finimundi, H, Daitz, C, Gagliardi, R, Pereira, G, Gomes, M, Gomes, A, Guimarães, A, Ninho, L, Jaeger, C, Pereira, L, Jorge, J, Cury, C, Kaiser, S, Almeida, A, Kalil, C, Radaelli, G, Kunz Sebba Barroso de Souza, W, Morales, K, Leaes, P, Luiz, Ro, Pimenta Almeida, J, Gozalo, A, Reis, G, Avellar, K, Reis Katz Weiand, L, Leipelt, J, Rocha, J, Barros, R, Rodrigues, L, Rocha, Mr, Rodrigues, A, Rodrigues, D, Rossi dos Santos, F, Pagnan, Lg, Sampaio, R, do Val, R, Saraiva, J, Vicente, C, Simoes, M, Carraro, A, Sobral Filho, D, Lustosa, E, Villas Boas, F, Almeida, M, Zimmermann, S, Zimmermann, Eb, Chompalova, B, Parishev, G, Denchev, S, Milcheva, N, Donova, T, Gergova, V, Georgiev, B, Kostova, E, Kinova, E, Hergeldjieva, V, Kamenova, P, Manolova, A, Vasilev, I, Mihov, A, Miteva, B, Mincheva, V, Stoyanovski, V, Nikolov, F, Vasilev, D, Pencheva, G, Kostov, K, Petranov, S, Milusheva, T, Popov, A, Staneva, A, Momchilova Lozeva, D, Todorov, G, Nyagina, M, Tumbev, H, Tumbeva, D, Tzekova, M, Kitova, 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G, St Hilaire, R, Morissette, A, Sussman, J, Kailey, P, Syan, G, Bobbie, C, Talajic, M, David, D, Talbot, P, Tremblay, M, Teitelbaum, I, Teitelbaum, J, Velthuysen, G, Giesbrecht, L, Wahby, R, Morley, A, Wharton, S, Caterini, T, Woodford, T, Balboa, W, Matus, Lr, Bugueño, C, Mondaca, Pm, Cobos, J, Obreque, C, Corbalan, R, Parada, A, Florenzano, F, Diaz, Pa, Lopetegui, M, Rebolledo, C, Manriquez, L, Silva, Lm, Martinez, D, Llamas, Rr, Opazo, M, Pérez, Mc, Pincetti, C, Carrasco, Gt, Potthoff, S, Staub, Jz, Campisto, Y, Stockins, B, Lara, Cl, Yovaniniz, P, Azua, Mg, Bai, F, Xu, Gl, Chen, Jz, Xie, Xd, Chen, Xp, Zhang, X, Dong, Yg, Feng, C, Fu, G, Zhang, P, Hong, K, You, Zg, Hong, L, Qiu, Y, Jiang, Xj, Qu, Z, Li, L, Liu, H, Li, Tf, Kong, Yq, Li, Wm, Liu, B, Li, Zq, Liu, Y, Liao, Dn, Gu, Xj, Liu, L, Lu, Zh, Ma, Sm, Yang, Zy, Wang, Dm, Qi, Sy, Wang, Gp, Shi, Xj, Wei, M, Huang, D, Wu, Sl, Li, Ye, Xu, Jh, Gu, Jy, Xu, Ym, Liang, Yz, Yang, K, Li, Ay, Yang, Yj, Zheng, X, Zheng, Y, Gao, M, Yin, Yh, Xu, Yp, Yu, B, Li, Ll, Yuan, Zy, Qiang, H, Zhang, Hq, Lin, Yn, Zhang, Z, Kang, H, Zhao, Rp, Han, Rj, Zhao, Xl, Wang, Jq, Zheng, Zq, Li, Bg, Zhou, Sx, Zhang, Yl, Accini, J, Accini, M, Cano, N, Pineda, Ll, Delgado Restrepo, J, Arroyave, C, Fernández Ruiz, R, Diaz, Ia, Hernandez, H, Delgado, P, Jaramillo Muñoz, C, Builes, A, Manzur, F, Rodriguez, Er, Moncada Corredor, M, Giraldo, Dl, Orozco Linares, L, Fonseca, J, Quintero, A, Gonzales, C, Sanchez Vallejo, G, Mejia, Ip, Bagatin, J, Carevic, V, Car, S, Jeric, M, Ciglenecki, N, Tusek, S, Ferri Certic, J, Romic, I, Francetic, I, Ausperger, Km, Jelic, V, Jurinjak, Sj, Knezevic, A, Buksa, B, Samardzic, P, Lukenda, Kc, Steiner, R, Kirner, D, Sutalo, K, Bakliza, Z, Vrazic, H, Lucijanic, T, Bar, M, Brodova, P, Berka, L, Kunkelova, V, Brtko, M, Burianova, H, Cermak, O, Elbl, L, Ferkl, R, Florian, J, Francek, L, Golan, L, Gregor, P, Honkova, M, Hubac, J, Jandik, J, Jarkovsky, P, Jelinek, Z, Jerabek, O, Jirmar, R, Kobza, R, Kochrt, M, Kostkova, G, 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M, Dinanian, S, Arfaoui, M, Hermida, J, Deruche, E, Kacet, S, Corbut, S, Poulard, J, Leparree, S, Roudaut, R, Duprat, C, Al Zoebi, A, Wurow, A, Bernhardt, P, Dichristin, U, Berrouschot, J, Vierbeck, S, Beyer Westendorf, J, Sehr, B, Bouzo, M, Schnelzer, P, Braun, R, Ladenburger, K, Buhr, M, Weihrauch, D, Contzen, C, Kara, M, Daut, W, Ayasse, D, Degtyareva, E, Kranz, P, Drescher, T, Herfurth, B, Faghih, M, Forck Boedeker, K, Schneider, K, Fuchs, R, Manuela, W, Grigat, C, Otto, A, Hartmann, A, Peitz, M, Heuer, H, Dieckheuer, U, Hoffmann, U, Dorn, S, Hoffmann, S, Schuppe, M, Horacek, T, Fink, P, Junggeburth, J, Schmid, S, Jungmair, W, Schoen, B, Kleinecke Pohl, U, Meusel, P, Koenig, H, Bauch, F, Lohrbaecher Kozak, I, Grosse, B, Lueders, S, Venneklaas, U, Luttermann, M, Wulf, M, Maus, O, Hoefer, K, Meissner, G, Braemer, U, Meyer Pannwitt, U, Frahm, E, Vogt, S, Muegge, A, Barbera, S, Mueller Glamann, M, Raddatz, K, Piechatzek, R, Lewinsky, D, Pohl, W, Proskynitopoulos, N, Kuhlmann, M, Rack, 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P, Menon, J, Francis, V, Namjoshi, D, Shelke, S, Narendra, J, Natarajan, S, Oomaan, A, Gurusamy, P, Angel, J, Purayil, Mp, Shams, S, Pandurangi, U, Sababathi, R, Parekh, P, Jasani, B, Patki, N, Babbar, A, Pinto, B, Kharalkar, H, Premchand, R, Jambula, H, Rao, M, Vuriya, A, Ravi Shankar, A, Reddy, R, Bekal, S, Barai, A, Saha, D, Gadepalli, R, Sant, H, Jadhav, D, Sarna, M, Arora, T, Sawhney, J, Singh, R, Sethi, K, Bansal, N, Sethia, A, Sethia, S, Shetty, G, Sudheer, R, Singh, G, Gupta, R, Srinivas, A, Thankaraj, L, Varma, S, Kaur, A, Vinod, Mv, Thakur, B, Zanwar, I, Dharmarao, A, Atar, S, Lasri, E, Dicker, D, Marcoviciu, D, Elias, M, Ron, Ga, Francis, A, Ghantous, R, Goldhaber, A, Goldhaber, M, Gottlieb, S, Rouwaida, S, Grossman, E, Dagan, T, Hasin, Y, Roshrosh, M, Hayek, T, Majdoub, A, Klainman, E, Genin, I, Lahav, M, Gilat, T, Ben Ari, M, Lishner, M, Karny, M, Ouzan, E, Givoni, H, Rozenman, Y, Logvinenko, S, Schiff, E, Sterlin, J, Shochat, M, Aloni, I, Swissa, M, Belatsky, V, Tsalihin, D, Kisos, D, Zeltser, D, Platner, N, Berni, A, Giovannelli, F, Boriani, G, Cervi, E, Comi, G, Peruzzotti, L, Cuccia, C, Forgione, C, De Caterina, R, De Pace, D, De Servi, S, Mariani, M, Di Lenarda, A, Mazzone, C, Di Pasquale, G, Di Niro, M, Fattore, L, Bosco, B, Grassia, V, Murena, E, Laffi, Gaggioli, G, Lo Pinto, G, Raggi, F, Marino, P, Francalacci, G, Babbolin, M, Bulgari, M, Penco, M, Lioy, E, PERRONE FILARDI, Pasquale, Marciano, C, Pirelli, S, Paradiso, G, Piseddu, G, Fenu, L, Raisaro, A, Granzow, K, Rasura, M, Cannoni, S, Severi, S, Breschi, M, Toschi, V, Gagliano, M, Zacà, V, Furiozzi, F, Hirahara, T, Akihisa, U, Masaki, W, Ajioka, M, Matsushita, C, Anzai, T, Mino, K, Arakawa, S, Tsukimine, A, Endo, H, Fujiwara, M, Fujii, K, Kozeni, S, Fujii, E, Kotera, M, Fujimoto, S, Omae, K, Fujimoto, K, Ichishita, Y, Fujita, T, Ito, Y, Fukamizu, S, Harada, J, Fukuda, N, Fujimoto, C, Funazaki, T, Yamaguchi, A, Furukawa, Y, Kamitake, C, Hagiwara, N, Naganuma, M, Hara, S, Kumagai, S, Harada, K, 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F, Pezzella, S, Kirk, D, Poulathas, A, Cush, S, Pratt, R, Neeper, L, Pribble, A, Lowe, K, Pudi, K, Sham, L, Pugeda, J, Ebert, J, Quadrel, M, Rafla, E, Quinlan, E, Reed, C, Quinn, J, Hemmen, C, Rama, P, Domingo, D, Redondo, V, Wroblewski, J, Renzi, M, Stanley, E, Richwine, R, Pazier, P, Riofrio, K, Braun, D, Robinson, J, Cherrico, M, Roehll, W, Hollihan, P, Rosado, Barnhorst, M, Rosado, J, Bamhorst, M, Rosen, R, Martin, C, Ross, S, Freeman, R, Ruoff, G, Nelson, T, Sacco, J, Ball, E, Samal, A, Schomburg, J, Sandberg, J, Lafave, J, Savin, V, Clifton, R, Schaefer, S, Fekete, A, Schneider, R, Schneider, W, Schulman, D, Mercer, S, Seals, A, Ullig, T, Holt, A, Seide, H, Mather, N, Shah, G, Witt, P, Shalaby, A, Seese, M, Shanes, J, Fleets, J, Shaoulian, E, Hren, A, Sheikh, K, Hengerer, T, Shih, H, Browning, J, Shoukfeh, M, Stephenson, L, Siler, T, Champagne, M, Simpson, P, Meyer, R, Singh, N, Turner, K, Singh, V, Nelson, M, Skierka, R, Hughes, B, Keene, R, Smith, R, Hodnett, P, Spangenthal, S, Thomason, L, Sperling, M, Vasquez, E, Spivack, E, Mccartney, P, Staniloae, C, Liu, M, Steljes, A, Cox, C, Struble, R, Vittitow, T, Suresh, D, Frost, J, Swerchowsky, V, Freemyer, D, Szulawski, I, Herwehe, S, Tahirkheli, N, Springer, K, Takata, T, Bruton, T, Talano, J, Leo, L, Tami, L, Corchado, D, Tatarko, M, Swauger, M, Tawney, K, Dastoli, K, Teague, S, Young, K, Tee, H, Mitchell, T, Teixeira, J, Southam, D, Torres, M, Tucker, P, Salas, L, Updegrove, J, Hanna, K, Val Mejias, J, Harrelson, Kg, Vemireddy, D, Cardoza, T, Verma, S, Parsons, T, Vicari, R, Warren, K, Vijay, N, Washam, M, Vossler, M, Kilcup, S, Walsh, R, Renaud, K, Ward, S, Locklear, T, Waxman, F, Sanchez, G, Weiss, R, St Laurent, B, Westcott, J, Williams, D, Gibson, C, Williams, R, Dowling, C, Willis, J, Vongerichten, S, Wood, K, Capasso Gulve, E, Worley, S, Pointer, S, Yarows, S, Sheehan, T, Yasin, M, Yi, J, Dongas, B, Yousuf, K, Zakhary, B, Curtis, S, Zeig, S, Mason, T, Zellner, C, Harden, M, Roper, E, Waseem, M, and Grammer, M. more...
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Male ,Pyridines ,[SDV]Life Sciences [q-bio] ,Embolism ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,0302 clinical medicine ,Edoxaban ,Atrial Fibrillation ,MESH: Double-Blind Method ,030212 general & internal medicine ,MESH: Warfarin ,Stroke ,MESH: Aged ,MESH: Middle Aged ,Cardiovascular diseases [NCEBP 14] ,Hazard ratio ,General Medicine ,MESH: Follow-Up Studies ,Middle Aged ,3. Good health ,MESH: Atrial Fibrillation ,Cardiovascular Diseases ,Anesthesia ,Cardiology ,Female ,Adult ,Aged ,Anticoagulants ,Double-Blind Method ,Follow-Up Studies ,Hemorrhage ,Humans ,Thiazoles ,Warfarin ,MESH: Hemorrhage ,Andexanet alfa ,medicine.drug ,medicine.medical_specialty ,MESH: Enoxaparin ,MESH: Anticoagulants ,MESH: Stroke ,Dabigatran ,03 medical and health sciences ,Internal medicine ,medicine ,MESH: Kaplan-Meier Estimate ,Rivaroxaban ,MESH: Humans ,business.industry ,MESH: Cardiovascular Diseases ,MESH: Adult ,medicine.disease ,Confidence interval ,MESH: Male ,chemistry ,business ,MESH: Female ,MESH: Embolism - Abstract
Contains fulltext : 125374.pdf (Publisher’s version ) (Open Access) BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P more...
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- 2013
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5. Storming the castle: Strategies for a successful Homeland Security Grant Application
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JD David M. McDonough, JD Rebecca A. Shore-Suslowitz, Joshua Easton, Jd, Ma, and JD Orit Zeevi
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Political science ,Emergency Medicine ,Homeland security ,General Medicine ,Public administration ,Safety, Risk, Reliability and Quality ,Safety Research - Published
- 2008
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6. Future Perspectives for Optimizing Oral Antiplatelet Therapy
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Easton Jd
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Burden of disease ,Secondary prevention ,medicine.medical_specialty ,Aspirin ,Arteriosclerosis ,business.industry ,Administration, Oral ,Thrombosis ,Clopidogrel ,medicine.disease ,Stroke ,Dipyridamole ,Neurology ,medicine ,Animals ,Humans ,Neurology (clinical) ,Medical emergency ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,Platelet Aggregation Inhibitors ,Forecasting ,medicine.drug - Abstract
Secondary prevention of stroke and other manifestations of atherothrombosis is essential if the burden of disease associated with these events is to be reduced. Therefore, it is important to identify patients most likely to benefit from antiplatelet therapy. There is a good rationale for combining antiplatelet agents with different modes of action, since different signalling pathways contribute to platelet activation. Based on the promising results obtained with an adenosine diphosphate receptor antagonist-aspirin combination in coronary stenting, several additional trials with clopidogrel plus aspirin are ongoing. They include CURE (Clopidogrel in Unstable angina to prevent Recurrent Events, in unstable angina and non-Q-wave myocardial infarction) and COMMIT (in acute myocardial infarction), which compare clopidogrel with placebo in patients receiving aspirin, and CREDO (Clopidogrel for Reduction of Events During extended Observation), a 1-year treatment follow-up to the clopidogrel arms of the CLASSICS trial (Clopidogrel Aspirin Stent International Cooperative Study). Planned trials with clopidogrel in neurology include SPS3 (Secondary Prevention of Small Subcortical Strokes, in patients with symptomatic lacunar stroke), and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients, in patients with stroke or transient ischaemic attack plus one additional risk factor), which will compare the efficacy of clopidogrel plus aspirin versus clopidogrel in reducing important ischaemic events. Combination therapy with an oral glycoprotein (GP) IIb/IIIa receptor antagonist plus aspirin has so far been less promising. Trials of three compounds – orbofiban, xemilofiban and sibrafiban – in combination with aspirin for secondary prevention in cardiac patients have reported increased mortality compared with aspirin alone. A similar effect was seen when sibrafiban monotherapy was compared directly with aspirin alone. Trials of newer oral GP IIb/IIIa inhibitors are under way or are planned. The combination of dipyridamole plus aspirin appears to be superior to aspirin alone for the prevention of stroke in patients with stroke or transient ischaemic attack; the effectiveness of this combination is being further investigated in ESPRIT (European/Australian Stroke Prevention in Reversible Ischaemia Trial). more...
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- 2001
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7. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
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Tricoci, P, Huang, Z, Held, C, Moliterno, Dj, Armstrong, Pw, Van de Werf, F, White, Hd, Aylward, Pe, Wallentin, L, Chen, E, Lokhnygina, Y, Pei, J, Leonardi, S, Rorick, Tl, Kilian, Am, Jennings, Lh, Ambrosio, G, Bode, C, Cequier, A, Cornel, Jh, Diaz, R, Erkan, A, Huber, K, Hudson, Mp, Jiang, L, Jukema, Jw, Lewis, Bs, Lincoff, Am, Montalescot, G, Nicolau, Jc, Ogawa, H, Pfisterer, M, Prieto, Jc, Ruzyllo, W, Sinnaeve, Pr, Storey, Rf, Valgimigli, M, Whellan, Dj, Widimsky, P, Strony, J, Harrington, Ra, Mahaffey, Kw, Huo, Y, Lixin, J, Isaza, D, Grande, P, Laine, M, Wong, L, Ofner, P, Yamaguchi, T, Park, Sj, Nordrehaug, Je, Providencia, L, Cheem, Th, Dalby, A, Betriu, A, Chen, Mf, Verheugt, F, Frye, Rl, Hochman, J, Steg, Pg, Bailey, Kr, Easton, Jd, Lincoff, A, Underwood, Fd, Wrestler, J, Larson, D, Vandyne, B, Kilian, A, Harmelin-Kadouri, R, Layton, L, Lipka, L, Petrauskas, S, Qidwai, M, Sorochuck, C, Temple, T, Mason, D, Sydlowski, D, Gallagher, B, Villasin, A, Beernaert, A, Douglas, S, 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Ca, Herczeg, B, Sereg, M, Butnaru, A, Lewis, B, Rosenschein, U, Mosseri, M, Turgeman, Y, Pollak, A, Shotan, A, Hammerman, H, Rozenman, Y, Gottlieb, S, Atar, S, Weiss, A, Marmor, A, Iakobishvili, Z, Mascia, F, De Cesare, N, Piovaccari, G, Ceravolo, R, Fiscella, A, Salvioni, A, Silvestri, O, Moretti, L, Severi, S, Carmina, Mg, De Caterina, R, Fattore, L, Terrosu, P, Trimarco, B, Ardissino, D, Uguccioni, L, Auguadro, C, Gregorio, G, De Ferrari, G, Testa, R, Evola, R, De Servi, S, Sganzerla, P, Vassanelli, C, Brunelli, C, Scherillo, M, Tamburino, C, Limido, A, Luzza, F, Percoco, Gf, Sinagra, G, Volpe, M, Crea, F, Fedele, F, Rasetti, G, Cinelli, F, Merlini, P, Sisto, F, Biancoli, S, Fresco, C, Corrada, E, Casolo, G, Santini, M, D'Alessandro, B, Antoniucci, D, Tuccillo, B, Assennato, P, Puccioni, E, Pasquetto, G, Perna, Gp, Morgagni, G, Takizawa, K, Kato, K, Oshima, S, Yagi, M, Asai, T, Kamiya, H, Hirokami, M, Sakota, S, Sueyoshi, A, Shimomura, H, Hashimoto, T, Miyahara, M, Matsumura, T, 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P, Larson, Le, Vasko, P, Pripp, Cm, Johansson, A, Moccetti, T, Corti, R, Pieper, M, Mach, F, Eberli, F, Jeger, R, Rickli, H, Vogt, P, Windecker, S, Wu, Cj, Kao, Hl, Charng, Mj, Chang, Kc, Chen, Zc, Tsa, Cd, Shyu, Kg, Lai, Wt, Hsieh, Ic, Hou, Jy, Yeh, Hi, Ueng, Kc, Yin, Wh, Timurkaynak, T, Yigit, Z, Yilmaz, M, Boyaci, A, Sahin, M, Goktekin, O, Bozkurt, E, Ercan, E, Yildirir, A, Muthusamy, R, Keeling, P, Levy, T, Zaman, A, Cohen, A, Gorog, D, Baumbach, A, Oldroyd, K, Kadr, H, Tait, G, Bellenger, N, Davis, G, Shakespeare, C, Senior, R, Bruce, D, Uren, N, Trouton, T, Ahsan, A, Hamed, A, Malik, I, Sarma, J, Millar-Craig, M, Robson, H, Kennon, S, Sprigings, D, Brodie, B, Kang, Gs, Thomas, G, Cheng, Sc, Espinoza, A, Kassas, S, Jafar, Z, Kumar, P, Izzo, M, Wiseman, A, Chandna, H, Felten, W, D'Urso, M, Gudipati, Cr, Coram, R, Gill, S, Bengtson, J, Chang, M, Raisinghani, A, Blankenship, J, Harbor, Wf, Kraft, P, Ashraf, R, Chambers, J, Albirini, A, Malik, A, Ziada, K, Slepian, M, Taussig, A, Vernon, H, Jetty, P, Islam, Ma, Canaday, D, Martin, T, Burchenal, Jj, Gencheff, N, Nygaard, T, Panchal, V, Merritt, R, Abrahams, L, Lambert, C, Reyes, P, Leimbach, W, Chhabra, A, Caputo, R, Imburgia, M, Erickson, B, Kleiman, N, Hunter, J, Dehning, M, Graham, B, Strain, J, White, Jk, Mcgarvey, J Jr, Henderson, D, Treasure, C 2nd, Mirro, M, Pancholy, S, Helmy, T, Westerhausen, D, Dib, N, Penny, W, Kim, H, Degregorio, M, Jay, D, Kmonicek, J, Berlowitz, M, Starling, M, Langevin, E, Nelson, R, Singer, A, Siachos, A, Gibson, G, Parrott, C, Held, J, Puleo, P, Wolford, T, Omar, B, Brilakis, E, Lewis, S, Heller, L, Brener, S, Addo, T, Lieberman, S, Eisenberg, D, Feldman, R, Waksman, R, Waltman, J, Schulman, S, Bounds, C, Voyce, S, Batchelor, W, Dobies, D, Pasnoori, V, Chandrashekhar, Y, Vetrovec, G, Azrin, M, Spriggs, D, Hirsch, C, Smucker, M, Chetcuti, S, Stella, R, Levite, H, Shoukfeh, M, Vidovich, M, Saucedo, J, Fintel, D, Low, R, Gellman, J, Ahsan, C, Unks, Dm, Tolleson, T, Ceccoli, H, Aggarwal, K, Bhaktaram, V, Olson, C, Decaro, M, Kaluski, E, Mehta, V, Puma, J, Singh, V, Fulmer, J, Lewis, D, Khadra, S, Staniloae, C, East, M, Sundram, Ps, Anderson, J, Wasserman, H, Guy, D, Brill, D, Kruse, K, Ebrahimi, R, Nguyen, T, Keating, F, Srivastava, R, Wassmer, P, Todd, J 3rd, Stein, M, Hamzeh, I, Laxson, D, Hodson, R, Puri, S, Vijayaraghavan, K, Gazmuri, R, Chu, A, Vijay, N, Rabinowitz, A, Block, T, Agarwal, H, Martin, J, Zetterlund, P, Fortuin, D, Macdonell, A 3rd, Zouzoulas, S, Chepuri, V, Schmalfuss, C, Karve, M, Aviles, R, Lieberman, E, Amlani, M, Murphy, S, Shapiro, T, Herzog, E, Ariani, K, Bhagwat, R, Hockstad, E, Kai, W, Saririan, M, Roth, R, Weiland, F, Atassi, K, Harjai, K, Muhlestein, J, Marsh, R, Shokooh, S, Nahhas, A, Labroo, A, Mayor, M, Koshy, S, Tariq, M, Rayos, G, Jones, S, Klugherz, B, Dewey, R, Rashid, Hu, Wohns, D, Feiring, A, Bowles, M, Rohrbeck, S, Monroe, Vs, De Gottlieb, A, Gumm, D, Brown, C 3rd, Chang, D, Kalaria, V, Minisi, A, Joumaa, M, Josephson, R, Kleczka, J, Silver, K, Coleman, P, Brachfeld, C, Saltiel, F, Reiner, J, Carell, E, Hanovich, G, Rosenberg, M, Das, G, Blick, D, and Universitat de Barcelona more...
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Male ,Pyridines ,medicine.medical_treatment ,Kaplan-Meier Estimate ,law.invention ,Lactones ,Randomized controlled trial ,law ,Thrombin receptor antagonist ,clopidogrel ,placebo ,thienopyridine derivative ,vorapaxar ,antithrombocytic agent ,lactone ,proteinase activated receptor 1 ,pyridine derivative ,Coronary Artery Bypass ,Vorapaxar ,Cardiovascular diseases [NCEBP 14] ,Drugs ,General Medicine ,Middle Aged ,Combined Modality Therapy ,Cardiovascular diseases ,Cardiovascular Diseases ,Cardiology ,Platelet aggregation inhibitor ,Drug Therapy, Combination ,Female ,Plaquetes sanguínies ,Intracranial Hemorrhages ,Major bleeding ,Medicaments ,medicine.drug ,medicine.medical_specialty ,Acute coronary syndrome ,Bypass cardiopulmonary ,Hemorrhage ,Pharmacotherapy ,Blood platelets ,Double-Blind Method ,Angioplasty ,Internal medicine ,medicine ,Humans ,Receptor, PAR-1 ,Acute Coronary Syndrome ,Aged ,business.industry ,Malalties cardiovasculars ,medicine.disease ,Surgery ,Bypass cardiopulmonar ,business ,Platelet Aggregation Inhibitors ,Follow-Up Studies - Abstract
Item does not contain fulltext BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P more...
- Published
- 2012
- Full Text
- View/download PDF
8. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study
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Khatri, B, Barkhof, F, Comi, G, Hartung, Hp, Kappos, L, Montalban, X, Pelletier, J, Stites, T, Wu, S, Holdbrook, F, Zhang auberson, L, Francis, G, Cohen, Ja, Cohen, J, Easton, Jd, Calandra, T, Dimarco, J, Hudson, L, Kesselring, J, Laupacis, A, Temkin, N, Weinshenker, B, Zarbin, M, Poppe, P, Luetic, G, Cristiano, E, Caceres, F, Garcea, O, Correale, J, Ballario, C, Piedrabuena, R, Pollard, J, Beran, R, Hodgkinson, S, Schwartz, R, Heard, R, King, J, Butzkueven, H, Maida, Em, Vass, K, Franta elmer, C, Berger, T, Aichner, F, Ladurner, G, Bissay, V, Sindic, C, D'Hooghe, M, Mulleners, E, Damasceno, B, Barreira, A, Naylor, R, Alvarenga, R, Bacellar, A, Haussen, S, Duquette, P, Antel, J, Lamontagne, A, Grand'Maison, F, Freedman, M, Christie, S, O'Connor, P, Vorobeychik, G, Devonshire, V, Ramadan, M, Hamdy, S, Reda, E, Hashem, S, Fouad, M, Lebrun frenay, C, Clanet, M, Brochet, B, Debouverie, M, Heinzlef, O, Ziemssen, T, Koehler, W, Tiel wilck, K, Bachus, R, Altmann, N, Faiss, J, Baum, K, Dressel, A, Luckner, K, Ebke, M, Stangel, M, Diener, Hc, Bethke, F, Limmroth, V, Maschke, M, Thoemke, F, Reifschneider, G, Diehm, R, Wildemann, B, Melms, A, Rauer, S, Karlbauer, G, Berthele, A, Lang, M, Tumani, H, Krauseneck, P, Klein, M, Papadimitriou, A, Karageorgiou, K, Liakopoulos, D, Tascos, N, Plaitakis, A, Papathanasopoulos, P, Panczel, G, Jakab, G, Csiba, L, Komoly, S, Csanyi, A, Bartos, L, Centonze, D, Pozzilli, C, Marrosu, Mg, Bertolotto, A, Mancardi, GIOVANNI LUIGI, Scarpini, E, Protti, A, Ghezzi, A, Capra, R, Bergamaschi, R, Gallo, P, Stecchi, S, Montanari, E, Tola, Mr, Amato, Mp, Silvestrini, M, Lugaresi, A, Trojano, M, Morra, Vb, Ruggieri, S, Patti, F, Kim, Sm, Lee, Kh, Kim, Hj, Park, Sp, Ginestal, R, Salgado, Av, Fontoura, P, Cunha, L, Sousa, L, Mj, Sá, Pedrosa, R, Arbizu, T, Arroyo, R, Merino, Ja, Fernandez, O, Izquierdo, G, Casanova, B, Antigüedad, A, Goebels, N, Young, C, Lee, M, Chaudhuri, A, Nicholas, R, Martinez, Ac, Preiningerova, J, Greco, D, Gross, J, Newman, S, Mitchell, G, Pawar, G, Freedman, Sm, Kaufman, M, Absher, J, Kantor, D, Ayala, R, Honeycutt, W, Shafer, S, Steingo, B, Delgado, S, Cascione, M, Brock, C, Keegan, A, Laganke, C, Hunter, S, Wilson, E, Mazhari, A, Bauer, W, Singer, B, Lynch, S, Rowe, V, Hutton, G, Gazda, S, Dihenia, B, Campagnolo, D, Chippendale, T, Ash, P, Jung, L, Olek, M., Radiology and nuclear medicine, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Khatri B, Barkhof F, Comi G, Hartung HP, Kappos L, Montalban X, Pelletier J, Stites T, Wu S, Holdbrook F, Zhang-Auberson L, Francis G, Cohen JA, TRANSFORMS Study Group, Lugaresi A, Diener, Hans Christoph (Beitragende*r), Khatri, B, Barkhof, F, Comi, G, Hartung, Hp, Kappos, L, Montalban, X, Pelletier, J, Stites, T, Wu, S, Holdbrook, F, Zhang Auberson, L, Francis, G, Cohen, Ja, BRESCIA MORRA, Vincenzo, Comi, Giancarlo, TRANSFORMS Study, Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie more...
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Adult ,Male ,medicine.medical_specialty ,multiple sclerosis, interferon beta, fingolimod, treatment ,Multiple Sclerosis ,Adolescent ,Medizin ,Phases of clinical research ,Relapsing-Remitting ,Injections, Intramuscular ,Young Adult ,Humans ,Adjuvants, Immunologic ,Interferon-beta ,Immunosuppressive Agents ,Multiple Sclerosis, Relapsing-Remitting ,Treatment Outcome ,Middle Aged ,Propylene Glycols ,Sphingosine ,Female ,law.invention ,Injections ,Randomized controlled trial ,law ,Immunologic ,analogs /&/ derivatives/therapeutic use ,Internal medicine ,Fingolimod Hydrochloride ,Medicine ,Adjuvants ,Young adult ,Intramuscular ,business.industry ,Multiple sclerosis ,Interferon beta-1a ,medicine.disease ,Fingolimod ,Surgery ,drug therapy/pathology/physiopathology ,Clinical research ,therapeutic use, Adolescent, Adult, Female, Humans, Immunosuppressive Agents ,therapeutic use, Injections ,Intramuscular, Interferon-beta ,therapeutic use, Male, Middle Aged, Multiple Sclerosis ,drug therapy/pathology/physiopathology, Propylene Glycols ,therapeutic use, Sphingosine ,analogs /&/ derivatives/therapeutic use, Treatment Outcome, Young Adult ,therapeutic use ,Settore MED/26 - Neurologia ,Neurology (clinical) ,business ,medicine.drug - Abstract
In a 12-month phase 3 study in patients with relapsing-remitting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and MRI outcomes compared with interferon beta-1a. We had two aims in our extension: to compare year 2 with year 1 in the switched patients to assess the effect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment groups as originally randomised to assess the effect of delaying the start of treatment with fingolimod. METHODS: Patients randomly assigned to receive 0.5 mg or 1.25 mg daily oral fingolimod in the core study continued with the same treatment in our extension; patients who originally received 30 μg weekly intramuscular interferon beta-1a were randomly reassigned (1:1) to receive either 0.5 mg or 1.25 mg fingolimod. The initial randomisation and dose of fingolimod assigned for the extension remained masked to the patients and investigators. As in the core study, re-randomisation was done centrally in blocks of six and stratified according to site. Our efficacy endpoints were annualised relapse rate (ARR), disability progression, and MRI outcomes. Our within-group analyses were based on the intention-to-treat and safety populations that entered our extension study. Our between-group analyses were based on the intention-to-treat and safety populations from the core study. This study is registered with ClinicalTrials.gov, number NCT00340834. FINDINGS: 1027 patients entered our extension and received the study drug, and 882 completed 24 months of treatment. Patients receiving continuous fingolimod showed persistent benefits in ARR (0.5 mg fingolimod [n=356], 0.12 [95% CI 0.08-0.17] in months 0-12 vs 0.11 [0.08-0.16] in months 13-24; 1.25 mg fingolimod [n=330], 0.15 [0.10-0.21] vs 0.11 [0.08-0.16]; however, in patients who initially received interferon beta-1a, ARR was lower after switching to fingolimod compared with the previous 12 months (interferon beta-1a to 0.5 mg fingolimod [n=167], 0.31 [95% CI 0.22-0.43] in months 0-12 vs 0.22 [0.15-0.31], in months 13-24 p=0.049; interferon beta-1a to 1.25 mg fingolimod [n=174], 0.29 [0.20-0.40] vs 0.18 [0.12-0.27], p=0.024). After switching to fingolimod, numbers of new or newly enlarging T2 and gadolinium (Gd)-enhancing T1 lesions were significantly reduced compared with the previous 12 months of interferon beta-1a therapy (p more...
- Published
- 2011
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9. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results
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Comi, G, O'Connor, P, Montalban, X, Antel, J, Radue, Ew, Karlsson, G, Pohlmann, H, Aradhye, S, Kappos, L, Easton, Jd, Kesselring, J, Weinshenker, Bg, Laupacis, A, Zarbin, M, Calandra, T, Temkin, N, Dimarco, J, Hudson, Ld, Durcan, L, Bar Or, A, Duquette, P, Bernier, G, Freedman, M, Maclean, H, Costello, F, Gray, Ta, Hohol, M, Devonshire, V, Oger, J, Hashimoto, S, Sørensen, Ps, Datta, P, Faber Rod JC, Frederiksen, J, Knudsen, S, Petrenaite, V, Färkkila, M, Harno, H, Halavaara, J, Elovaara, I, Kuusisto, H, Palmio, J, Airas, L, Kaasinen, V, Laaksonen, M, Vermersch, P, Pelletier, J, Feuillet, L, Suchet, L, Mauch, E, Gunser, C, Oberbeck, K, Rieckmann, P, Buttmann, M, Klein, M, Ghezzi, A, Zaffaroni, M, Baldini, S, Mancardi, G, Cioli, F, Capello, E, Rodegher, M, Radaelli, M, Pozzilli, C, Onesti, Emanuela, Romano, Silvia, Czlonkowska, A, Litwin, T, Darda Ledzion, L, Kwiecinski, H, Golebiowski, M, Podlecka, A, Cunha, L, Sousa, L, Matias, F, Pedrosa, R, Almeida, M, Pena, Je, de Sá, J, Ferreira, J, Rosa, M, Arbizu, T, Carmona, O, Casado, V, Tintore, M, Pelayo, R, Arroyo, R, Bartolome, M, De las Heras, V, Casanova, B, Bosca, I, Fernandez, O, Leon, A, Romero, F, Izquierdo, G, Gamero, M, Garcia, Jm, Kuhle, J, Mehling, M, Achtnichts, L, Goebels, N, Skulina, C, Waskoenig, J, Bates, D, Nichols, P, Bendfeldt, K, de Vera, A, Gruenbauer, W., Ben Dahan, David, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS) more...
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Oral ,Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Time Factors ,Adolescent ,Phases of clinical research ,Administration, Oral ,Kaplan-Meier Estimate ,Relapsing-Remitting ,administration /&/ dosage/adverse effects ,Placebo ,law.invention ,Pulmonary function testing ,03 medical and health sciences ,Disability Evaluation ,Young Adult ,0302 clinical medicine ,Multiple Sclerosis, Relapsing-Remitting ,Randomized controlled trial ,law ,Sphingosine ,Internal medicine ,Fingolimod Hydrochloride ,administration /&/ dosage/adverse effects/analogs /&/ derivatives ,medicine ,Humans ,Adverse effect ,business.industry ,Fingolimod ,Magnetic Resonance Imaging ,diagnosis/drug therapy/pathology ,Administration ,Oral, Adolescent, Adult, Disability Evaluation, Female, Humans, Immunosuppressive Agents ,administration /&/ dosage/adverse effects, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Multiple Sclerosis ,diagnosis/drug therapy/pathology, Propylene Glycols ,administration /&/ dosage/adverse effects, Sphingosine ,administration /&/ dosage/adverse effects/analogs /&/ derivatives, Time Factors, Treatment Outcome, Young Adult ,3. Good health ,Surgery ,Clinical trial ,Treatment Outcome ,Neurology ,Propylene Glycols ,030220 oncology & carcinogenesis ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Immunosuppressive Agents ,medicine.drug - Abstract
In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7—36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15—24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88—89%) or new T2 lesions (70—78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20—0.21, and 68—73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3—5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme. more...
- Published
- 2010
10. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study
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O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, Ew, de Vera, A, Pohlmann, H, Kappos, L, Easton, Jd, Kesselring, J, Weinshenker, Bg, Laupacis, A, Zarbin, M, Calandra, T, Temkin, N, Dimarco, J, Hudson, Ld, Durcan, L, Bar Or, A, Duquette, P, Bernier, G, Freedman, M, Maclean, H, Costello, F, Gray, Ta, Hohol, M, Devonshire, V, Hashimoto, S, Sørensen, Ps, Datta, P, Faber Rod JC, Frederiksen, J, Knudsen, S, Petrenaite, V, Harno, H, Färkkila, M, Halavaara, J, Elovaara, I, Kuusisto, H, Palmio, J, Airas, L, Kaasinen, V, Laaksonen, M, Vermersch, P, Pelletier, J, Feuillet, L, Suchet, L, Mauch, E, Gunser, C, Oberbeck, K, Rieckmann, P, Buttmann, M, Klein, M, Ghezzi, A, Zaffaroni, M, Baldini, S, Mancardi, G, Cioli, F, Capello, E, Rodegher, M, Radaelli, M, Pozzilli, C, Onesti, Emanuela, Romano, Silvia, Czlonkowska, A, Litwin, T, Darda Ledzion, L, Kwiecinski, H, Golebiowski, M, Podlecka, A, Nojszewska, K, Cunha, L, Sousa, L, Matias, F, Pedrosa, R, Almeida, M, Pena, Je, de Sá, J, Ferreira, J, Rosa, M, Arbizu, T, Carmona, O, Casado, V, Tintore, M, Pelayo, R, Arroyo, R, Bartolome, M, De las Heras, V, Casanova, B, Bosca, I, Fernandez, O, Leon, A, Romero, F, Izquierdo, G, Gamero, M, Garcia, Jm, Kuhle, J, Mehling, M, Achtnichts, L, Goebels, N, Skulina, C, Waskoenig, J, Bates, D, Nichols, P, Bendfeldt, K, Karlsson, G, Burtin, P, Zubal, T., Oconnor, P., Comi, G., Montalban, X., Antel, J., Radue, E. W., De Vera, A., Pohlmann, H., Kappos, L., and Radaelli, M more...
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Male ,Time Factors ,Administration, Oral ,Kaplan-Meier Estimate ,Gastroenterology ,Severity of Illness Index ,law.invention ,Immunosuppressive Agent ,Disability Evaluation ,Randomized controlled trial ,law ,Oral administration ,Sphingosine ,hemic and lymphatic diseases ,Multiple Sclerosi ,administration /&/ dosage ,Respiratory Function Test ,Incidence ,Middle Aged ,Fingolimod ,Propylene Glycol ,Magnetic Resonance Imaging ,Respiratory Function Tests ,Tolerability ,Administration ,Female ,Oral, Adolescent, Adult, Disability Evaluation, Double-Blind Method, Female, Humans, Immunosuppressive Agents ,administration /&/ dosage, Incidence, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis ,drug therapy/mortality, Propylene Glycols ,administration /&/ dosage, Respiratory Function Tests ,methods, Severity of Illness Index, Sphingosine ,administration /&/ dosage/analogs /&/ derivatives, Time Factors, Young Adult ,medicine.symptom ,Immunosuppressive Agents ,medicine.drug ,Human ,Oral ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Time Factor ,Adolescent ,Placebo ,methods ,Lesion ,Young Adult ,Double-Blind Method ,Internal medicine ,administration /&/ dosage/analogs /&/ derivatives ,Severity of illness ,medicine ,drug therapy/mortality ,Humans ,business.industry ,Fingolimod Hydrochloride ,Surgery ,Clinical trial ,Propylene Glycols ,Neurology (clinical) ,business - Abstract
Objective:: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS:: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS:: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS:: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity. © 2009 AAN Enterprises, Inc. more...
- Published
- 2009
11. Performance of carotid ultrasound in evaluating candidates for carotid endarterectomy is optimized by an approach based on clinical outcome rather than accuracy
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Edward Feldmann, Ward R, Easton Jd, and J. L. Wilterdink
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Duplex ultrasonography ,medicine.medical_specialty ,Systole ,medicine.medical_treatment ,Carotid endarterectomy ,Sensitivity and Specificity ,Cohort Studies ,medicine ,Humans ,Carotid Stenosis ,False Positive Reactions ,False Negative Reactions ,Endarterectomy ,Advanced and Specialized Nursing ,Endarterectomy, Carotid ,Ultrasonography, Doppler, Duplex ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Patient Selection ,Ultrasound ,medicine.disease ,Cerebral Angiography ,Survival Rate ,Stenosis ,Cerebrovascular Disorders ,Carotid Arteries ,Treatment Outcome ,ROC Curve ,Angiography ,Neurology (clinical) ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Algorithms ,Cerebral angiography ,Forecasting ,Information Systems - Abstract
Background and Purpose The best method of selecting endarterectomy candidates for cerebral angiography is controversial. Carotid duplex ultrasound (CDUS) is widely used, but its performance varies across institutions. The clinical utility of CDUS could be improved with test criteria based on patient outcome rather than test accuracy. Methods In 155 carotid bifurcations studied by CDUS and cerebral angiography, the degree of angiographic stenosis was measured by a reader, blinded to CDUS, using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. We calculated accuracy, sensitivity, and specificity for predicting ≥70% angiographic carotid stenosis of different peak systolic frequencies (PSF) measured by CDUS and generated a receiver operator characteristic (ROC) curve. We used NASCET outcome data and published data on angiographic complications to define relative “costs” of false-positive and false-negative CDUS, and we determined the point on the ROC curve representing the CDUS criterion with the highest clinical utility. We compared projected morbidity and mortality rates for 1000 hypothetical endarterectomy candidates resulting from the use of the most accurate CDUS criterion versus the CDUS criterion with the highest clinical utility by ROC analysis. Results While PSF ≥8 kHz had the highest CDUS accuracy (93%), its projected stroke and death rate due to CDUS error was 10.4/1000. On the other hand, PSF ≥7 kHz, defined by ROC analysis to have the highest clinical utility, had a lower morbidity and mortality rate of 6.8/1000. Conclusions The use of ROC analysis and available outcome data can improve the performance of CDUS in selecting endarterectomy candidates for cerebral angiography. more...
- Published
- 1996
12. TREATMENT TO PREVENT MIGRAINE-RELATED STROKE
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Olesen, J, Welch, Kma, Carolei, Antonio, and Easton, Jd
- Published
- 1993
13. Storming the castle: Strategies for a successful Homeland Security Grant Application
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McDonough, JD, David M., primary, Easton, JD, MA, Joshua, additional, Shore-Suslowitz, JD, Rebecca A., additional, and Zeevi, JD, Orit, additional
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- 2008
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14. Cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in atrial fibrillation.
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Kamel H, Easton JD, Johnston SC, Kim AS, Kamel, Hooman, Easton, J Donald, Johnston, S Claiborne, and Kim, Anthony S
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- 2012
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15. Effect of clopidogrel on the rate and functional severity of stroke among high vascular risk patients: a prespecified substudy of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial.
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Hankey GJ, Hacke W, Easton JD, Johnston SC, Mas JL, Brennan DM, Bhatt DL, Fox KA, Topol EJ, CHARISMA Trial Investigators, Hankey, Graeme J, Hacke, Werner, Easton, J Donald, Johnston, S Claiborne, Mas, Jean-Louis, Brennan, Danielle M, Bhatt, Deepak L, Fox, Keith A A, and Topol, Eric J more...
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- 2010
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16. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on...
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Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, Hatsukami TS, Higashida RT, Johnston SC, Kidwell CS, Lutsep HL, Miller E, Sacco RL, Easton, J Donald, Saver, Jeffrey L, Albers, Gregory W, Alberts, Mark J, Chaturvedi, Seemant, Feldmann, Edward, and Hatsukami, Thomas S more...
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- 2009
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17. Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk.
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Eikelboom JW, Hankey GJ, Thom J, Bhatt DL, Steg PG, Montalescot G, Johnston SC, Steinhubl SR, Mak K, Easton JD, Hamm C, Hu T, Fox KAA, Topol EJ, and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance Investigators more...
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- 2008
18. Statin use and sex-specific stroke outcomes in patients with vascular disease.
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Bushnell CD, Griffin J, Newby LK, Goldstein LB, Mahaffey KW, Graffagnino CA, Harrington RA, White HD, Simes RJ, Califf RM, Topol EJ, Easton JD, Bushnell, Cheryl D, Griffin, Jeffrey, Newby, L Kristin, Goldstein, Larry B, Mahaffey, Kenneth W, Graffagnino, Carmelo A, Harrington, Robert A, and White, Harvey D more...
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- 2006
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19. Performance of carotid ultrasound in evaluating candidates for carotid endarterectomy is optimized by an approach based on clinical outcome rather than accuracy.
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Wilterdink JL, Feldmann E, Easton JD, Ward R, Wilterdink, J L, Feldmann, E, Easton, J D, and Ward, R
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- 1996
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20. Seizure recurrence after a first, unprovoked seizure
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Easton Jd and Hart Rg
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medicine.medical_specialty ,Pediatrics ,Epilepsy ,Adult patients ,medicine.medical_treatment ,Seizure recurrence ,medicine.disease ,First seizure ,Anticonvulsant ,Arts and Humanities (miscellaneous) ,Recurrence ,Seizures ,Recurrent seizures ,medicine ,Humans ,Neurology (clinical) ,Psychiatry ,Psychology - Abstract
The management of patients with a single, unprovoked seizure is controversial. The likelihood of seizure recurrence after a first seizure has profound social, vocational, and emotional implications for the patient. The issue of whether or not to use anticonvulsant medication in these patients is an important part of this controversy and may be substantially affected by the true probability of seizure recurrence. The last word about recurrence of seizures following an initial, unprovoked seizure has yet to be written. It is widely stated that only about 30% of adult patients who experience a single, unprovoked seizure will subsequently develop recurrent seizures (epilepsy). This figure is derived from several studies that differed in their patient populations and in their patients' use of anticonvulsants (Table). Further, the critical interval from the first seizure to entry into the study was often not defined in these studies. This interval is critical because all epileptics more...
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- 1986
21. Diphenylhydantoin and epilepsy management
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Easton Jd
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Phenytoin ,medicine.medical_specialty ,Ideal (set theory) ,Epilepsy ,business.industry ,medicine.medical_treatment ,MEDLINE ,Administration, Oral ,General Medicine ,medicine.disease ,Injections, Intramuscular ,Anticonvulsant ,Phenobarbital ,Injections, Intravenous ,Internal Medicine ,Medicine ,Humans ,business ,Intensive care medicine ,medicine.drug - Abstract
Many epileptics are receiving less than ideal anticonvulsant treatment; therefore, some basic but often overlooked principles of epilepsy management are discussed. Diphenylhydantoin is an ...
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- 1972
22. Dieting and Peroneal Nerve Palsy
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Sherman Dg and Easton Jd
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Peroneal nerve palsy ,medicine.medical_specialty ,Weight loss ,business.industry ,medicine ,General Medicine ,medicine.symptom ,business ,Dieting ,Surgery - Abstract
In seven patients, peroneal nerve palsies developed while they were on weight-reduction diets. Five palsies were unilateral; two, bilateral. All patients recovered following diet modification. Therapeutic weight loss, of itself, can cause foot-drop. The prognosis is uniformly good. ( JAMA 238:230-231, 1977) more...
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- 1977
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23. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
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Albers GW, Amarenco P, Easton JD, Sacco RL, and Teal P
- Abstract
This chapter about treatment and prevention of stroke is part of the 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke (AIS), we recommend administration of i.v. tissue plasminogen activator (tPA), if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with extensive and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B). For unselected patients with AIS of > 3 h but < 6 h, we suggest clinicians not use i.v. tPA (Grade 2A). For patients with AIS, we recommend against streptokinase (Grade 1A) and suggest clinicians not use full-dose anticoagulation with i.v. or subcutaneous heparins or heparinoids (Grade 2B). For patients with AIS who are not receiving thrombolysis, we recommend early aspirin therapy, 160 to 325 mg qd (Grade 1A). For AIS patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low molecular weight heparins or heparinoids (Grade 1A); and for patients who have contraindications to anticoagulants, we recommend use of intermittent pneumatic compression devices or elastic stockings (Grade 1C). In patients with acute intracerebral hematoma, we recommend the initial use of intermittent pneumatic compression (Grade 1C+). In patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A) including aspirin, 50 to 325 mg qd; the combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid; or clopidogrel, 75 mg qd. In these patients, we suggest use of the combination of aspirin and extended-release dipyridamole, 25/200 mg bid, over aspirin (Grade 2A) and clopidogrel over aspirin (Grade 2B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1C+). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low molecular weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase. [ABSTRACT FROM AUTHOR] more...
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- 2004
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24. Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE-SPECT ESUS Trial
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Victor J. Del Brutto, Han‐Christoph Diener, J. Donald Easton, Christopher B. Granger, Lisa Cronin, Eva Kleine, Claudia Grauer, Martina Brueckmann, Kazunori Toyoda, Peter D. Schellinger, Philippe Lyrer, Carlos A. Molina, Aurauma Chutinet, Christopher F. Bladin, Conrado J. Estol, Ralph L. Sacco, Institut Català de la Salut, [Del Brutto VJ] Department of Neurology, University of Miami Miller School of Medicine, Miami, FL. [Diener HC] Department of Neurology, University DuisburgEssen, Essen, Germany. [Easton JD] Department of Neurology, University of California, San Francisco, CA. [Granger CB] Duke Clinical Research Institute, Durham, NC. [Cronin L] Boehringer Ingelheim Pharma, Burlington, Ontario, Canada. [Kleine E] Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. [Molina CA] Unitat d’Ictus i Hemodinàmica Cerebral, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus more...
- Subjects
Male ,Clinical Trials and Supportive Activities ,Medizin ,Cardiovascular Diseases::Vascular Diseases::Embolism and Thrombosis::Embolism [DISEASES] ,Cardiorespiratory Medicine and Haematology ,técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Clinical Research ,Risk Factors ,enfermedades cardiovasculares::enfermedades vasculares::embolia y trombosis::embolia [ENFERMEDADES] ,Humans ,embolic stroke of undetermined source ,Malalties cerebrovasculars - Factors de risc ,Tomography ,Tomography, Emission-Computed, Single-Photon ,Embolic Stroke ,Embòlia - Factors de risc ,Aspirin ,Prevention ,Neurosciences ,Cerebral Infarction ,stroke predictors ,Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::Stroke [DISEASES] ,Brain Disorders ,Dabigatran ,Stroke ,Intracranial Embolism ,Emission-Computed ,Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,enfermedades cardiovasculares::enfermedades vasculares::trastornos cerebrovasculares::accidente cerebrovascular [ENFERMEDADES] ,Cardiology and Cardiovascular Medicine ,secondary prevention ,Single-Photon - Abstract
Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance 2 DS 2 ‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA 2 DS 2 ‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02239120. more...
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- 2022
25. Relation between aspirin dose, all-cause mortality, and bleeding in patients with recent cerebrovascular or coronary ischemic events (from the BRAVO Trial)
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Aronow HD, Califf RM, Harrington RA, Vallee M, Graffagnino C, Shuaib A, Fitzgerald DJ, Easton JD, Van de Werf F, Diener H, Ferguson J, Koudstaal PJ, Amarenco P, Theroux P, Davis S, Topol EJ, and BRAVO Trial more...
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- 2008
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26. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.
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Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas J, Montalescot G, Pearson TA, and Steg PG more...
- Abstract
Background: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.Methods: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.Results: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).Conclusions: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.). [ABSTRACT FROM AUTHOR] more...- Published
- 2006
27. Time to treatment and disability attributed to index stroke in the POINT trial.
- Author
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Balali P, Easton JD, Johnston SC, and Cucchiara B
- Subjects
- Humans, Male, Female, Time Factors, Aged, Middle Aged, Treatment Outcome, Risk Factors, Recovery of Function, Ischemic Attack, Transient drug therapy, Ischemic Attack, Transient diagnosis, Ischemic Attack, Transient physiopathology, Aspirin therapeutic use, Aspirin adverse effects, Aspirin administration & dosage, Platelet Aggregation Inhibitors adverse effects, Platelet Aggregation Inhibitors therapeutic use, Disability Evaluation, Clopidogrel therapeutic use, Clopidogrel adverse effects, Dual Anti-Platelet Therapy adverse effects, Time-to-Treatment, Ischemic Stroke diagnosis, Ischemic Stroke drug therapy, Ischemic Stroke physiopathology, Functional Status
- Abstract
Background: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, dual antiplatelet therapy (DAPT) was associated with reduced disability attributable to the index stroke compared to antiplatelet monotherapy. However, it is unknown whether earlier treatment with DAPT versus aspirin is associated with greater benefit., Methods: We analyzed patients enrolled in POINT with minor ischemic stroke who had available data recording the treatment initiation time and modified Rankin Scale (mRS) at 90 days. Patients were randomized to DAPT (aspirin plus clopidogrel) vs. aspirin alone within 12 h of symptom onset. We estimated the effect of DAPT on disability (defined as mRS>1) ascribed to the index event and major hemorrhage at 90 days, stratified by tertiles of time from symptom onset-to-treatment-initiation., Results: A total of 2559 patients were included; median onset-to-treatment-initiation time was 8.3 h (IQR:5.8-11.0). Comparing DAPT to aspirin, the rate of disability attributed to the index event at 90-day follow-up was 5.1 % vs. 8.6 % (OR 0.57; 95 % CI:0.33-0.99) in patients treated <6.7 h, 7.5 % vs. 9.9 % (OR 0.74; 95 % CI:0.45-1.19) in those treated 6.7-10.0 h, and 8.6 % vs. 10.6 % (OR 0.80; 95 % CI:0.50-1.26) in those treated >10.0 h after symptom onset (p for interaction=0.65). There was no difference in major hemorrhage across time strata., Conclusions: While not statistically significant, these results suggest the possibility of greater efficacy at reducing disability ascribed to minor stroke with earlier treatment with DAPT compared to aspirin., Registration: URL: https://www., Clinicaltrials: gov; Identifier: NCT00991029., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.) more...
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- 2024
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28. Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.
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Li J, Meng X, Shi FD, Jing J, Gu HQ, Jin A, Jiang Y, Li H, Johnston SC, Hankey GJ, Easton JD, Chang L, Shi P, Wang L, Zhuang X, Li H, Zang Y, Zhang J, Sun Z, Liu D, Li Y, Yang H, Zhao J, Yu W, Wang A, Pan Y, Lin J, Xie X, Jin WN, Li S, Niu S, Wang Y, Zhao X, Li Z, Liu L, Zheng H, and Wang Y more...
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- Humans, Male, Female, Double-Blind Method, Middle Aged, Aged, Treatment Outcome, China, C-Reactive Protein analysis, Adult, Colchicine administration & dosage, Colchicine therapeutic use, Colchicine adverse effects, Ischemic Attack, Transient drug therapy, Ischemic Stroke drug therapy, Ischemic Stroke prevention & control
- Abstract
Objectives: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3)., Design: Multicentre, double blind, randomised, placebo controlled trial., Setting: 244 hospitals in China between 11 August 2022 and 13 April 2023., Participants: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled., Interventions: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days., Main Outcome Measures: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat., Results: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83)., Conclusions: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L., Trial Registration: ClinicalTrials.gov, NCT05439356., Competing Interests: Declaration of interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from National Key R&D Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.) more...
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- 2024
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29. Baseline Stroke Risk and Efficacy of Dual-Antiplatelet Therapy: A Post Hoc Analysis of the POINT Trial.
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Daghlas I, Johnston SC, Easton JD, and Kim AS
- Subjects
- Humans, Aspirin adverse effects, Drug Therapy, Combination, Hemorrhage chemically induced, Hemorrhage epidemiology, Hemorrhage complications, Platelet Aggregation Inhibitors adverse effects, Risk Factors, Treatment Outcome, Clinical Trials as Topic, Ischemic Attack, Transient drug therapy, Ischemic Attack, Transient epidemiology, Ischemic Attack, Transient complications, Ischemic Stroke drug therapy, Stroke epidemiology, Stroke prevention & control, Stroke complications
- Abstract
Background: High-risk transient ischemic attacks and minor ischemic strokes are followed by a variable risk of ischemic stroke. We aimed to determine how baseline stroke risk modified the efficacy of clopidogrel-aspirin (referred to here as dual-antiplatelet therapy [DAPT]) for transient ischemic attack and minor ischemic stroke., Methods: We performed an unplanned secondary analysis of the POINT trial (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke). We first evaluated the associations of the CHA
2 DS2 -VASc and stroke prognosis instrument II (SPI-II) scores with the risk of incident ischemic stroke and major hemorrhage (intracranial hemorrhage or major systemic hemorrhage). We then tested for heterogeneity of the relative and absolute treatment effect of DAPT relative to aspirin across low- and high-risk patient subgroups., Results: A total of 4841 trial participants were included in this analysis, with 2400 participants assigned to treatment with short-term DAPT and 2430 participants to treatment with aspirin and placebo. The dichotomized SPI-II score, but not the CHA2 DS2 -VASc score ( P =0.18), was associated with the risk of incident ischemic stroke. A high-risk SPI-II score (>3) was associated with greater risk of incident ischemic stroke (hazard ratio of incident ischemic stroke relative to low-risk SPI-II score of 1.84 [95% CI, 1.44-2.35]; P <0.001) and numerically greater risk of major hemorrhage though not meeting statistical significance (hazard ratio, 1.80 [95% CI, 0.90-3.57]; P =0.10). The relative risk reduction with DAPT was similar across SPI-II strata ( Pinteraction =0.31). The absolute risk reduction for ischemic stroke with DAPT compared with aspirin was nearly 4-fold higher (2.80% versus 0.76%; number needed to treat, 31 versus 131) in the high-risk SPI-II stratum relative to the low-risk stratum. The absolute risk increase for major hemorrhage with DAPT compared with aspirin was 3-fold higher (0.84% versus 0.30%; number needed to harm, 119 versus 331) in the high-risk SPI-II stratum relative to the low-risk stratum., Conclusions: Stratification by baseline stroke risk identifies a patient subgroup that derives greater absolute benefit from treatment with DAPT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00991029., Competing Interests: Disclosures Dr Johnston reports research funding from AstraZeneca AB and Sanofi US Services, Inc, has served as a consultant for AstraZeneca AB, Bristol Myers Squibb Company, and Johnson & Johnson International, and has served on the Data and Safety Monitoring Board of Everest Contract Research Organization. more...- Published
- 2024
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30. Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3): Rationale and design of a multicenter randomized placebo-controlled trial.
- Author
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Wang Y, Li J, Johnston SC, Hankey GJ, Easton JD, Meng X, Shi FD, Wang Y, Zhao X, Li Z, Liu L, Gu H, Jiang Y, Wang A, Pan Y, Jing J, Niu S, and Li H
- Subjects
- Humans, Platelet Aggregation Inhibitors therapeutic use, Aspirin therapeutic use, Clopidogrel therapeutic use, Colchicine therapeutic use, Ischemic Attack, Transient drug therapy, Stroke drug therapy, Stroke chemically induced, Ischemic Stroke drug therapy
- Abstract
Background: Anti-inflammatory therapy using colchicine has reduced recurrent vascular events in patients with coronary heart disease., Design: Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3) is a randomized, double-blind, placebo-controlled multicenter trial, in which 8,238 patients with acute minor-to-moderate ischemic stroke (NIHSS ⩽ 5) or high-risk transient ischemic attack (TIA) (ABCD
2 score ⩾4) and a high-sensitivity CRP (hsCRP) level of ⩾2 mg/L will be randomly assigned within 24 h of symptom onset to colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or matching placebo, on a background of optimal medical therapy. The study will have 90% power to detect a 25% reduction in the primary efficacy outcome of any stroke within 3 months of randomization. Adverse events potentially related to the use of colchicine will also be analyzed. The primary analysis will be by intention to treat., Trial Registry Name: Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3); URL: https://clinicaltrials.gov/ct2/show/NCT05439356?cond=CHANCE-3&draw=2&rank=1; Registration number : NCT05439356. more...- Published
- 2023
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31. Subsequent ischemic stroke and tobacco smoking: A secondary analysis of the POINT trial.
- Author
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Lang AE, de Havenon A, Mac Grory B, Henninger N, Shu L, Furie KL, Easton JD, Kim A, Johnston SC, and Yaghi S
- Subjects
- Humans, Aspirin therapeutic use, Clopidogrel therapeutic use, Hemorrhage chemically induced, Neoplasm Recurrence, Local chemically induced, Platelet Aggregation Inhibitors therapeutic use, Smoking adverse effects, Tobacco Smoking, Ischemic Attack, Transient chemically induced, Ischemic Stroke epidemiology, Stroke chemically induced
- Abstract
Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk., Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively., Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97-1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56-0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37-1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40-7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08-6.21), p = 0.032), p for interaction = 0.613., Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Dr. de Havenon is funded by NIH-NINDS, has received investigator initiated clinical research funding from Regeneron, AMGEN, and AMAG pharmaceuticals, has received consultant fees from Integra and Novo Nordisk, has equity in TitinKM and Certus, and receives author fees from UpToDate. Dr. Easton received funding for his role in the POINT trial which was sponsored by NIH/NINDS but received drug and placebo from Sanofi. Dr. Johnston received research support from AstraZeneca. The POINT trial was sponsored by NIH/NINDS but received drug and placebo from Sanofi. Dr. Lang reported previously owning stock in Walmart, Target, and Johnson & Johnson outside the submitted work., (© European Stroke Organisation 2022.) more...
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- 2023
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32. Review and update of the concept of embolic stroke of undetermined source.
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Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, and Ntaios G
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- Administration, Oral, Anticoagulants therapeutic use, Aspirin, Humans, Platelet Aggregation Inhibitors therapeutic use, Embolic Stroke, Intracranial Embolism complications, Ischemic Stroke, Stroke diagnosis, Stroke drug therapy, Stroke etiology
- Abstract
Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge., (© 2022. Springer Nature Limited.) more...
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- 2022
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33. The Concept of Transient Ischemic Attack-Reply.
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Easton JD and Johnston SC
- Subjects
- Humans, Ischemic Attack, Transient
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- 2022
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34. Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE-SPECT ESUS Trial.
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Del Brutto VJ, Diener HC, Easton JD, Granger CB, Cronin L, Kleine E, Grauer C, Brueckmann M, Toyoda K, Schellinger PD, Lyrer P, Molina CA, Chutinet A, Bladin CF, Estol CJ, and Sacco RL
- Subjects
- Aspirin therapeutic use, Cerebral Infarction, Dabigatran therapeutic use, Humans, Male, Risk Factors, Tomography, Emission-Computed, Single-Photon, Embolic Stroke, Intracranial Embolism diagnostic imaging, Intracranial Embolism etiology, Stroke chemically induced, Stroke prevention & control
- Abstract
Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE-SPECT ESUS (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow-up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83-2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23-2.32]), male sex (HR, 1.60 [95% CI, 1.27-2.02]), and CHA
2 DS2 -VASc ≥4 (HR, 1.55 [95% CI, 1.15-2.08] and HR, 1.66 [95% CI, 1.21-2.26] for scores of 4 and ≥5, respectively) versus CHA2 DS2 -VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE-SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high-risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120. more...- Published
- 2022
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35. Infarct on Brain Imaging, Subsequent Ischemic Stroke, and Clopidogrel-Aspirin Efficacy: A Post Hoc Analysis of a Randomized Clinical Trial.
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Rostanski SK, Kvernland A, Liberman AL, de Havenon A, Henninger N, Mac Grory B, Kim AS, Easton JD, Johnston SC, and Yaghi S
- Subjects
- Aged, Aspirin therapeutic use, Cerebral Infarction drug therapy, Clopidogrel therapeutic use, Drug Therapy, Combination, Female, Humans, Male, Neuroimaging, Platelet Aggregation Inhibitors therapeutic use, Treatment Outcome, Ischemic Attack, Transient drug therapy, Ischemic Stroke, Stroke diagnostic imaging, Stroke drug therapy
- Abstract
Importance: In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, acute treatment with clopidogrel-aspirin was associated with significantly reduced risk of recurrent stroke. There may be specific patient groups who are more likely to benefit from this treatment., Objective: To investigate whether the association of clopidogrel-aspirin with stroke recurrence in patients with minor stroke or high-risk transient ischemic attack (TIA) is modified by the presence of infarct on imaging attributed to the index event (index imaging) among patients enrolled in the POINT Trial., Design, Setting, and Participants: In the POINT randomized clinical trial, patients with high-risk TIA and minor ischemic stroke were enrolled at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand from May 28, 2010, to December 19, 2017. In this post hoc analysis, patients were divided into 2 groups according to whether they had an acute infarct on index imaging. All POINT trial participants with information available on the presence or absence of acute infarct on index imaging were eligible for this study. Univariable Cox regression models evaluated associations between the presence of an infarct on index imaging and subsequent ischemic stroke and evaluated whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Data were analyzed from July 2020 to May 2021., Exposures: Presence or absence of acute infarct on index imaging., Main Outcomes and Measures: The primary outcome is whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk., Results: Of the 4881 patients enrolled in POINT, 4876 (99.9%) met the inclusion criteria (mean [SD] age, 65 [13] years; 2685 men [55.0%]). A total of 1793 patients (36.8%) had an acute infarct on index imaging. Infarct on index imaging was associated with ischemic stroke during follow-up (hazard ratio [HR], 3.68; 95% CI, 2.73-4.95; P < .001). Clopidogrel-aspirin vs aspirin alone was associated with decreased ischemic stroke risk in patients with an infarct on index imaging (HR, 0.56; 95% CI, 0.41-0.77; P < .001) compared with those without an infarct on index imaging (HR, 1.11; 95% CI, 0.74-1.65; P = .62), with a significant interaction association (P for interaction = .008)., Conclusions and Relevance: In this study, the presence of an acute infarct on index imaging was associated with increased risk of recurrent stroke and a more pronounced benefit from clopidogrel-aspirin. Future work should focus on validating these findings before targeting specific patient populations for acute clopidogrel-aspirin treatment. more...
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- 2022
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36. Time to Retire the Concept of Transient Ischemic Attack.
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Easton JD and Johnston SC
- Subjects
- Humans, Ischemic Attack, Transient, Terminology as Topic
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- 2022
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37. Antiplatelet Use and Ischemic Stroke Risk in Minor Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the POINT Trial.
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Anadani M, de Havenon A, Henninger N, Kuohn L, Mac Grory B, Furie KL, Kim AS, Easton JD, Johnston SC, and Yaghi S
- Subjects
- Aged, Female, Humans, Ischemic Attack, Transient drug therapy, Ischemic Attack, Transient prevention & control, Male, Middle Aged, Platelet Aggregation Inhibitors administration & dosage, Dual Anti-Platelet Therapy, Ischemic Stroke drug therapy, Ischemic Stroke prevention & control, Platelet Aggregation Inhibitors therapeutic use, Secondary Prevention methods
- Abstract
Background and Purpose: Dual antiplatelet therapy has been shown to reduce the risk of recurrent stroke in patients with minor stroke or transient ischemic attack. However, whether the effect of dual antiplatelet therapy is modified by pretreatment antiplatelet status is unclear., Methods: This is a post hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Patients were divided into 2 groups based on pretreatment antiplatelet use. The primary outcome was ischemic stroke within 90 days of randomization., Results: We included 4881 patients of whom 41% belonged to the no pretreatment antiplatelet. Ischemic stroke occurred in 6% and 5% in the antiplatelet pretreatment and no antiplatelet pretreatment, respectively. Antiplatelet pretreatment was not associated with the risk of ischemic stroke (adjusted hazard ratio, 1.05 [95% CI, 0.81-137]) or risk of major hemorrhage (hazard ratio, 1.10 [95% CI, 0.55-2.21]; P =0.794). The effect of dual antiplatelet therapy on recurrent ischemic stroke risk was not different in patients who were on antiplatelet before randomization (adjusted hazard ratio, 0.69 [95% CI, 0.50-0.94]) as opposed to those who were not (adjusted hazard ratio, 0.75 [95% CI, 0.50-1.12]), P for interaction = 0.685., Conclusions: In patients with minor stroke and high-risk transient ischemic attack, dual antiplatelet therapy reduces the risk of ischemic stroke regardless of premorbid antiplatelet use. more...
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- 2021
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38. Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial.
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Bahit MC, Sacco RL, Easton JD, Meyerhoff J, Cronin L, Kleine E, Grauer C, Brueckmann M, Diener HC, Lopes RD, Brainin M, Lyrer P, Wachter R, Segura T, and Granger CB
- Subjects
- Administration, Oral, Age Factors, Aged, Body Mass Index, Double-Blind Method, Female, Humans, Hypertension blood, Hypertension drug therapy, Hypertension epidemiology, Male, Middle Aged, Predictive Value of Tests, Recurrence, Risk Factors, Aspirin administration & dosage, Atrial Fibrillation blood, Atrial Fibrillation complications, Atrial Fibrillation drug therapy, Atrial Fibrillation epidemiology, Dabigatran administration & dosage, Embolic Stroke blood, Embolic Stroke epidemiology, Embolic Stroke etiology, Embolic Stroke prevention & control, Models, Cardiovascular, Natriuretic Peptide, Brain blood, Peptide Fragments blood
- Abstract
Background: A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke attributable to underlying AF. The RE-SPECT ESUS trial (Randomized, Double-Blind Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) provides an opportunity to assess predictors for developing AF and associated recurrent stroke., Methods: RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF., Results: In the multivariable model, older age (odds ratio for 10-year increase, 1.99 [95% CI, 1.78-2.23]; P <0.001), hypertension (odds ratio, 1.36 [95% CI, 1.03-1.79]; P =0.0304), diabetes (odds ratio, 0.74 [95% CI, 0.56-0.96]; P =0.022), and body mass index (odds ratio for 5-U increase, 1.29 [95% CI, 1.16-1.43]; P <0.001) were independent predictors of AF during the study. In a sensitivity analysis restricted to 1117 patients with baseline NT-proBNP (N-terminal prohormone of brain natriuretic peptide) measurements, only older age and higher NT-proBNP were significant independent predictors of AF. Performance of several published predictive models was assessed, including HAVOC (AF risk score based on hypertension, age ≥75 years, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, and coronary artery disease) and CHA
2 DS2 -VASc (stroke risk score based on congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, previous stroke, transient ischemic attack or thromboembolism [doubled], vascular disease, age 65 to 74 years, and sex category [female]) scores, and higher scores were associated with higher rates of developing AF., Conclusions: Besides age, the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after embolic stroke of undetermined source. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120. more...- Published
- 2021
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39. Carotid Stenosis and Recurrent Ischemic Stroke: A Post-Hoc Analysis of the POINT Trial.
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Yaghi S, de Havenon A, Rostanski S, Kvernland A, Mac Grory B, Furie KL, Kim AS, Easton JD, Johnston SC, and Henninger N
- Subjects
- Aged, Aged, 80 and over, Brain Ischemia diagnostic imaging, Carotid Stenosis diagnostic imaging, Dual Anti-Platelet Therapy methods, Female, Follow-Up Studies, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors administration & dosage, Recurrence, Retrospective Studies, Stroke diagnostic imaging, Aspirin administration & dosage, Brain Ischemia drug therapy, Carotid Stenosis drug therapy, Clopidogrel administration & dosage, Stroke drug therapy
- Abstract
Background and Purpose: Randomized trials demonstrated the benefit of dual antiplatelet therapy in patients with minor ischemic stroke or high-risk transient ischemic attack. We sought to determine whether the presence of carotid stenosis was associated with increased risk of ischemic stroke and whether the addition of clopidogrel to aspirin was associated with more benefit in patients with versus without carotid stenosis., Methods: This is a post-hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) that randomized patients with minor ischemic stroke or high-risk transient ischemic attack within 12 hours from last known normal to receive either clopidogrel plus aspirin or aspirin alone. The primary predictor was the presence of ≥50% stenosis in either cervical internal carotid artery. The primary outcome was ischemic stroke. We built Cox regression models to determine the association between carotid stenosis and ischemic stroke and whether the effect of clopidogrel was modified by ≥50% carotid stenosis., Results: Among 4881 patients enrolled POINT, 3941 patients met the inclusion criteria. In adjusted models, ≥50% carotid stenosis was associated with ischemic stroke risk (hazard ratio, 2.45 [95% CI, 1.68-3.57], P <0.001). The effect of clopidogrel (versus placebo) on ischemic stroke risk was not significantly different in patients with <50% carotid stenosis (adjusted hazard ratio, 0.68 [95% CI, 0.50-0.93], P =0.014) versus those with ≥50% carotid stenosis (adjusted hazard ratio, 0.88 [95% CI, 0.45-1.72], P =0.703), P value for interaction=0.573., Conclusions: The presence of carotid stenosis was associated with increased risk of ischemic stroke during follow-up. The effect of added clopidogrel was not significantly different in patients with versus without carotid stenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429. more...
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- 2021
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40. Evaluation of Systolic Blood Pressure, Use of Aspirin and Clopidogrel, and Stroke Recurrence in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial.
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de Havenon A, Johnston SC, Easton JD, Kim AS, Sheth KN, Lansberg M, Tirschwell D, Mistry E, and Yaghi S
- Subjects
- Aged, Cohort Studies, Female, Humans, Male, Middle Aged, Recurrence, Risk Factors, Secondary Prevention methods, Severity of Illness Index, United States, Aspirin therapeutic use, Blood Pressure drug effects, Clopidogrel therapeutic use, Dual Anti-Platelet Therapy methods, Ischemic Attack, Transient drug therapy, Platelet Aggregation Inhibitors therapeutic use, Stroke drug therapy
- Abstract
Importance: Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk., Objective: To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP., Design, Setting, and Participants: This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021., Exposures: Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (<140 mm Hg vs ≥140 mm Hg) × treatment group (aspirin vs DAPT)., Main Outcomes and Measures: The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA)., Results: Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP × treatment) was significant (P for interaction = .03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72; P = .004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02; P = .08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (P for interaction = .02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55; P = .002)., Conclusions and Relevance: In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence. more...
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- 2021
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41. Newly Diagnosed Atrial Fibrillation After Transient Ischemic Attack Versus Minor Ischemic Stroke in the POINT Trial.
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Kamel H, Farrant M, Easton JD, Sposato LA, Elm JJ, Underwood E, and Johnston SC
- Subjects
- Aged, Atrial Fibrillation complications, Atrial Fibrillation drug therapy, Female, Follow-Up Studies, Humans, Ischemic Attack, Transient drug therapy, Ischemic Stroke drug therapy, Male, Middle Aged, Retrospective Studies, Risk Factors, Time Factors, Atrial Fibrillation diagnosis, Ischemic Attack, Transient etiology, Ischemic Stroke etiology, Platelet Aggregation Inhibitors therapeutic use
- Abstract
Background Atrial fibrillation/flutter (AF) after transient ischemic attack (TIA) has not been well studied. We compared the likelihood of new AF diagnosis after ischemic stroke versus TIA. Methods and Results The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial enrolled adults within 12 hours of minor ischemic stroke or high-risk TIA. Our exposure was index event type (ischemic stroke versus TIA). The primary analysis used the original trial definition of TIA (resolution of symptoms/signs). In secondary analyses, TIA cases with infarction on neuroimaging were reclassified as strokes. Our primary outcome was a new AF diagnosis, ascertained from adverse event and treatment interruption/discontinuation reports. We calculated C-statistics for variables associated with newly diagnosed AF. We used Kaplan-Meier survival statistics and Cox models adjusted for demographics and vascular risk factors. Excluding 49 subjects with baseline AF, 2746 patients had index stroke and 2086 patients had index TIA. During the 90-day follow-up, 106 patients had newly diagnosed AF. Cumulative risks of AF were 2.7% (95% CI, 2.1%-3.4%) after stroke and 2.0% (95% CI, 1.5%-2.7%) after TIA ( P =0.15). After reclassifying index events by neuroimaging, cumulative AF risk was higher after stroke (2.7%; 95% CI, 2.2%-3.4%) than TIA (1.8%; 95% CI, 1.3%-2.5%) ( P =0.04). Index event type had negligible predictive utility (C-statistic, 0.54). Conclusions Among patients with cerebral ischemia, the distinction between TIA versus minor stroke did not stratify the risk of subsequent AF diagnosis, implying that patients with TIA should undergo similar heart-rhythm monitoring strategies as patients with ischemic stroke. more...
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- 2021
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42. Dabigatran or Aspirin in East Asian Patients With Embolic Stroke of Undetermined Source: RE-SPECT ESUS Subgroup Analysis.
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Uchiyama S, Toyoda K, Lee BC, Liou CW, Wong LKS, Grauer C, Brueckmann M, Taniguchi A, Urano Y, and Easton JD
- Subjects
- Asian People, Aspirin adverse effects, Cohort Studies, Dabigatran adverse effects, Double-Blind Method, Embolic Stroke etiology, Embolic Stroke mortality, Asia, Eastern, Follow-Up Studies, Hemorrhage chemically induced, Hemorrhage epidemiology, Humans, Platelet Aggregation Inhibitors adverse effects, Recurrence, Treatment Outcome, Aspirin therapeutic use, Dabigatran therapeutic use, Embolic Stroke drug therapy, Platelet Aggregation Inhibitors therapeutic use
- Abstract
Background and Purpose: We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with embolic stroke of undetermined source in the RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source)., Methods: Patients with a recent embolic stroke of undetermined source were randomized to dabigatran (150 or 110 mg BID) or aspirin (100 mg QD). The primary efficacy outcome was recurrent stroke; the primary safety outcome was major bleeding. The East Asia cohort was compared with patients from all other countries (non-East Asia cohort)., Results: Overall, 988 of 5390 patients (18%) were randomized in East Asia. During a median follow-up of 18.8 months, there was no statistically significant difference in recurrent stroke (hazard ratio, 0.65 [95% CI, 0.41-1.03]) or major bleeding (hazard ratio, 1.04 [95% CI, 0.57-1.91]) in East Asian patients receiving dabigatran versus aspirin. Death from any cause occurred more often in the dabigatran versus the aspirin group (hazard ratio, 3.98 [95% CI, 1.32-12.01])., Conclusions: The treatment effect of dabigatran versus aspirin was consistent between cohorts, with no apparent superiority for dabigatran over aspirin in preventing recurrent stroke in patients with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120. more...
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- 2021
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43. Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale: Results From RE-SPECT ESUS.
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Diener HC, Chutinet A, Easton JD, Granger CB, Kleine E, Marquardt L, Meyerhoff J, Zini A, and Sacco RL
- Subjects
- Adolescent, Adult, Anticoagulants, Aspirin adverse effects, Dabigatran adverse effects, Double-Blind Method, Embolic Stroke complications, Female, Humans, Ischemic Stroke complications, Male, Middle Aged, Platelet Aggregation Inhibitors pharmacology, Secondary Prevention, Young Adult, Aspirin administration & dosage, Dabigatran administration & dosage, Embolic Stroke drug therapy, Embolic Stroke prevention & control, Embolism complications, Foramen Ovale, Patent complications, Ischemic Stroke drug therapy, Ischemic Stroke prevention & control
- Abstract
Background and Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed., Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS., Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43-1.14]) for ischemic stroke., Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120. more...
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- 2021
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44. Methodologies for pragmatic and efficient assessment of benefits and harms: Application to the SOCRATES trial.
- Author
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Evans SR, Knutsson M, Amarenco P, Albers GW, Bath PM, Denison H, Ladenvall P, Jonasson J, Easton JD, Minematsu K, Molina CA, Wang Y, Wong KL, and Johnston SC
- Subjects
- Adult, Humans, Odds Ratio, Platelet Aggregation Inhibitors therapeutic use, Pragmatic Clinical Trials as Topic methods, Research Design, Treatment Outcome, Aspirin therapeutic use, Ischemic Attack, Transient drug therapy, Randomized Controlled Trials as Topic methods, Stroke drug therapy, Ticagrelor therapeutic use
- Abstract
Background/aims: Standard approaches to trial design and analyses can be inefficient and non-pragmatic. Failure to consider a range of outcomes impedes evidence-based interpretation and reduces power. Traditional approaches synthesizing information obtained from separate analysis of each outcome fail to incorporate associations between outcomes and recognize the cumulative nature of outcomes in individual patients, suffer from competing risk complexities during interpretation, and since efficacy and safety analyses are often conducted on different populations, generalizability is unclear. Pragmatic and efficient approaches to trial design and analyses are needed., Methods: Approaches providing a pragmatic assessment of benefits and harms of interventions, summarizing outcomes experienced by patients, and providing sample size efficiencies are described. Ordinal outcomes recognize finer gradations of patient responses. Desirability of outcome ranking is an ordinal outcome combining benefits and harms within patients. Analysis of desirability of outcome ranking can be based on rank-based methodologies including the desirability of outcome ranking probability, the win ratio, and the proportion in favor of treatment. Partial credit analyses, involving grading the levels of the desirability of outcome ranking outcome similar to an academic test, provides an alternative approach. The methodologies are demonstrated using the acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes study (SOCRATES; NCT01994720), a randomized clinical trial., Results: Two 5-level ordinal outcomes were developed for SOCRATES. The first was based on a modified Rankin scale. The odds ratio is 0.86 (95% confidence interval = 0.75, 0.99; p = 0.04) indicating that the odds of worse stroke categorization for a trial participant assigned to ticagrelor is 0.86 times that of a trial participant assigned to aspirin. The 5-level desirability of outcome ranking outcome incorporated and prioritized survival; the number of strokes, myocardial infarction, and major bleeding events; and whether a stroke event was disabling. The desirability of outcome ranking probability and win ratio are 0.504 (95% confidence interval = 0.499, 0.508; p = 0.10) and 1.11 (95% confidence interval = 0.98, 1.26; p = 0.10), respectively, implying that the probability of a more desirable result with ticagrelor is 50.4% and that a more desirable result occurs 1.11 times more frequently on ticagrelor versus aspirin., Conclusion: Ordinal outcomes can improve efficiency through required pre-specification, careful construction, and analyses. Greater pragmatism can be obtained by composing outcomes within patients. Desirability of outcome ranking provides a global assessment of the benefits and harms that more closely reflect the experience of patients. The desirability of outcome ranking probability, the proportion in favor of treatment, the win ratio, and partial credit can more optimally inform patient treatment, enhance the understanding of the totality of intervention effects on patients, and potentially provide efficiencies over standard analyses. The methods provide the infrastructure for incorporating patient values and estimating personalized effects. more...
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- 2020
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45. Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation.
- Author
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Diener HC, Hankey GJ, Easton JD, Lip GYH, Hart RG, and Caso V
- Abstract
The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.) more...
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- 2020
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46. Efficacy of Clopidogrel for Prevention of Stroke Based on CYP2C19 Allele Status in the POINT Trial.
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Meschia JF, Walton RL, Farrugia LP, Ross OA, Elm JJ, Farrant M, Meurer WJ, Lindblad AS, Barsan W, Ching M, Gentile N, Ross M, Nahab F, Easton JD, Kim AS, Zurita KG, Cucchiara B, and Johnston SC
- Subjects
- Aged, Alleles, Cerebral Infarction drug therapy, Cytochrome P-450 CYP2C19 genetics, Female, Genotype, Humans, Ischemic Attack, Transient genetics, Male, Middle Aged, Platelet Aggregation Inhibitors therapeutic use, Treatment Outcome, Clopidogrel therapeutic use, Cytochrome P-450 CYP2C19 drug effects, Ischemic Attack, Transient drug therapy, Stroke drug therapy
- Abstract
Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT., Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death., Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09-1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32-1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33)., Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029. more...
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- 2020
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47. Antithrombotic Treatment of Embolic Stroke of Undetermined Source: RE-SPECT ESUS Elderly and Renally Impaired Subgroups.
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Diener HC, Sacco RL, Easton JD, Granger CB, Bar M, Bernstein RA, Brainin M, Brueckmann M, Cronin L, Donnan G, Gdovinová Z, Grauer C, Kleine E, Kleinig TJ, Lyrer P, Martins S, Meyerhoff J, Milling T, Pfeilschifter W, Poli S, Reif M, Rose DZ, Šaňák D, and Schäbitz WR more...
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- Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Male, Middle Aged, Recurrence, Aspirin administration & dosage, Aspirin pharmacokinetics, Dabigatran administration & dosage, Dabigatran pharmacokinetics, Fibrinolytic Agents administration & dosage, Fibrinolytic Agents pharmacokinetics, Intracranial Embolism blood, Intracranial Embolism drug therapy, Kidney Diseases blood, Kidney Diseases drug therapy, Stroke blood, Stroke drug therapy
- Abstract
Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120. more...
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- 2020
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48. Disability After Minor Stroke and Transient Ischemic Attack in the POINT Trial.
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Cucchiara B, Elm J, Easton JD, Coutts SB, Willey JZ, Biros MH, Ross MA, and Johnston SC
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- Aged, Aspirin therapeutic use, Clopidogrel therapeutic use, Double-Blind Method, Female, Humans, Intracranial Hemorrhages complications, Intracranial Hemorrhages epidemiology, Male, Middle Aged, Myocardial Infarction complications, Myocardial Infarction epidemiology, Platelet Aggregation Inhibitors therapeutic use, Predictive Value of Tests, Recurrence, Risk Factors, Sex Factors, Treatment Outcome, Disability Evaluation, Ischemic Attack, Transient epidemiology, Stroke complications
- Abstract
Background and Purpose- While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods- The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results- At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% versus 14.3%; odds ratio, 0.97 [95% CI, 0.82-1.14]; P =0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% versus 4.0%; odds ratio, 0.73 [95% CI, 0.53-1.01]; P =0.06) and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% versus 7.4%; odds ratio, 0.78 [95% CI, 0.62-0.99]; P =0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% versus 6.0%; odds ratio, 0.74 [95% CI, 0.57-0.96]; P =0.02). In multivariate analysis, age, subsequent ischemic stroke, serious adverse events, and major bleeding were significantly associated with disability in TIA; for those with stroke, female sex, hypertension, or diabetes mellitus, National Institutes of Health Stroke Scale score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions- In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029. more...
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- 2020
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49. Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial.
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Easton JD, Denison H, Evans SR, Knutsson M, Amarenco P, Albers GW, Ladenvall P, Minematsu K, Molina CA, Wang Y, Wong KL, and Johnston SC
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- Hemorrhage chemically induced, Humans, Observer Variation, Proportional Hazards Models, Research Personnel, Secondary Prevention, Stroke epidemiology, Aspirin therapeutic use, Hemorrhage epidemiology, Ischemic Attack, Transient drug therapy, Mortality, Myocardial Infarction epidemiology, Platelet Aggregation Inhibitors therapeutic use, Stroke drug therapy, Ticagrelor therapeutic use
- Abstract
Background: Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited., Aims: This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators., Methods: SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages., Results: The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78-1.01) when calculated on adjudicator-assessed events and 0.88 (0.78-1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75-0.99) based on the adjudicators' diagnoses and 0.85 (0.75-0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%., Conclusions: In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication., Trial Registration: ClinicalTrials.gov Identifier: NCT01994720. more...
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- 2019
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50. Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trials.
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Pan Y, Elm JJ, Li H, Easton JD, Wang Y, Farrant M, Meng X, Kim AS, Zhao X, Meurer WJ, Liu L, Dietrich D, Wang Y, and Johnston SC
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- Humans, Ischemic Attack, Transient diagnosis, Ischemic Stroke diagnosis, Multicenter Studies as Topic methods, Risk Factors, Treatment Outcome, Aspirin administration & dosage, Clopidogrel administration & dosage, Dual Anti-Platelet Therapy methods, Ischemic Attack, Transient drug therapy, Ischemic Stroke drug therapy, Platelet Aggregation Inhibitors administration & dosage, Randomized Controlled Trials as Topic methods
- Abstract
Importance: Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA., Objective: To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA., Design, Setting, and Participants: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019., Interventions: In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset., Main Outcomes and Measures: The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage., Results: The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant., Conclusions and Relevance: In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA. more...
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- 2019
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