@article { , title = {Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial}, abstract = {Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6\%] participants vs 105 [7\%]; adjusted common odds ratio [cOR] 0·90, 95\% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95\% CI 2·05–3·16, p}, doi = {10.1016/S0140-6736(17)32849-0}, eissn = {1474-547X}, issn = {0140-6736}, issue = {10123}, journal = {Lancet}, pages = {850-859}, publicationstatus = {Published}, publisher = {Elsevier}, url = {https://nottingham-repository.worktribe.com/output/918616}, volume = {391}, year = {2018}, author = {Bath, Philip M.W. and Christensen, L M and Woodhouse, Lisa J. and Bentsen, L and Appleton, Jason P. and Krarup Hansen, C and Beridze, M. and Thomsen, T T and Christensen, Hanne and Kruuse, C and Dineen, Robert A. and Jensen, H H and Duley, Lelia and Hansen, S S and England, Timothy J. and Petrovic, V and Flaherty, Katie and Beridze, N and Havard, Diane and Kakabadze, N and Heptinstall, Stan and Kherkheulidze, T and James, Marilyn and Kakabadze, D and Krishnan, Kailash and Toidze, I and Markus, H.S. and Lobjanidze, N and Montgomery, Alan A. and Akiashvili, N and Pocock, Stuart J. and ATevdoradze, and Randall, Marc and Khizanishvili, N and Ranta, A. and Tsanava, T and Robinson, Thompson G. and Taylor, R and Scutt, Polly and Iniesta, I and Venables, Graham S. and Kok, J and Sprigg, Nikola and Duignan, J and Funnell, M and Cariga, P and Rodriguez, M and Watson, I J and Tennant, S and Macleod, M and Furnace, J and Gow, H and Irvine, J and Joyson, A and Nelson, S and Taylor, V and Smith, M and Bellfield, R and Hairsine, B and Davies, R and Dodd, A and Corrigan, J and Doherty, M and Ahmed, A and Denniss, C and Johnson-Holland, S and Kay, K A and Icart Palau, R and Auld, G and Daboo, P and Erande, R and Grimwood, G and Hove, D and Howaniec, L and Redjep, O and Rangasamay, R and Butt, G and Sandler, D and Reddan, J and Stafford, S and McIlmoyle, J and Maguire, S and Murphy, P and Chambers, J and Guthrie, L and Osborn, M and Steele, A and Burn, M and Benford, A and Misra, A and Hilton, D and O'Brien, E and Amis, E and Finlay, S and Mitchell, J and Geraghty, O and Harvey, K and Hazel, B and Mashate, S and Wilding, P and Sajid, M and Ball, M and Gascoyne, R and Sivakumar, R and Wright, A and Chatterjee, K and Booth, S and Eccleson, H and Kelly, C and Leason, S and Perkins, C and Bruce, D and Brown, E and Clayton, S and Garside, M and Rogers, G and Lawrence, E and Mahmood, S and Watchurst, C and Chadha, D and Glover, L and Holford, L and Smith, K and Walstow, D and Williams, R and O'Shea, L and Goodsell, J and Athulathmudali, C and Barbon, E and Namushi, R and Jacob, P and Johnson, L and Morse, D and McGhee, C and Speirs, O and Atkinson, S and Peacocke, A and Langhorne, P and Graham, R and Wright, F and McAlpine, C and Ravindrane, A and Bajoriene, M and Matter, L and Windebank, S and Giallombardo, E and Dellafera, D and Eglinton, C and Wilson, J and Broughton, D and Chapman, K and Dixon, L and Zaidi, M and Ayes, K and Kessell, J and Manawadu, D and Adegbaju, O and Aeron-Thomas, J and Anderson, K and Brigden, A and Cattermole, E and Good, J and Hassan, S and Khoromana, E and Lee-Carbon, L and Marks, K and Mckenzie, E and Sikondari, N and Cooper, M and Whysall, K and Wynter, I and Bamford, J and Hassan, A and Wanklyn, P and Kambafwile, M and Makawa, L and Waugh, D and Veraque, E and Soliman, M G G and Arif, S and Brown, R and Butler, S and Hewitt, C and Hindle, J and Pusalkar, A and Beadle, H and Chan, K and Siddiqui, M and Dangri, P and Buddha, S and Asokanathan, A and Mistri, A and Eveson, D and Musarrat, K and Manning, L and Anand, S and Christian, P and Khan, S and Patel, C and Sein, M and Banns, J and Gibson, E and Gordon, T and Gruenbeck, Y and Wong, S and Datta, P and Bateman, G and Jackson, L and Needle, A and Duodu, Y and Oliver, R and Padilla-Harris, C and Barber, M and Esson, D and Brodie, F and McInnes, C and Fotherby, K and Butler, D and Morgan, D and Preece, K and Willberry, A and Dent, M and Hammonds, F and Hunt, J and Vernon, C and O'Kane, D and Faola, F and Lai, P and O'Callaghan, J and Smith, C and Price, C and Lakey, R and Riddell, V and Smith, A and Storey, G and Munshi, S and Buck, A and Clarke, J and Gilzeane, N and Godfrey, M and Keshvara, R and Richardson, C and Roffe, J and Ryan, L and Shelton, F and Sunman, W and Tittle, A and Tomlinson, J and Whittamore, K and Wilkes, G and Owusu-Agyei, P and Temple, N and Mangion, D and Hardwick, A and Netherton, K and MohdNor, A and Hyams, B and Norman, S and Persad, N and Ragab, S and Dickson, C and Dube, J and Jinks, E and Knops, K and Wadams, B and Ali, K and Gaylard, J and Spurling, G and Sztriha, L and Ajao, T and Alao, M and KChan, F and Webster, P and HowardT JDobson, P and Hyatt, L and Sims, D and Cunningham, J and Esisi, B and Cassidy, T and Bokhari, M and McClelland, B and Mokoena, B and Gunathilagan, G and Jones, S and Reader, M and Thomas, G and Tilby, S and Findlay, P and Barrett, F and Leslie, F and Ross, S and Shread, I and Okwera, J and Howe, J and Harrington, F and Courtauld, G and Schofield, C and Donnelly, R and Maddula, M and Scott, J and Beavan, J and Muhidden, K and Memon, I and Clarke, M and Hedstrom, A and Mills, L and Hemsley, A and Bowring, A and Boxall, L and Kingwell, H and Keenan, S and Roughan, C and Manoj, A and Cox, P and Fletcher, G and Lopez, P and Emsley, H and Gregary, B and McLoughlin, A and Raj, S and Roffe, C and Abano, N and Barry, A and Butler, A and Carpio, R and Castro, K and Finney, K and Gomm, S and Hiden, J and Grocott, J and Lyjko, S and Maguire, H and Remegoso, A and Sanyal, R and Stevens, S and Natarajan, I and Chembala, J and Muddegowda, G and Warusevitane, A and Blight, A and Balazikova, O and Lawlor, C and Shaw, L and Button, D and Howcroft, D and Lucas, S and Madigan, B and McCann, S and Dixit, A and Barkat, A and Davis, J and Fawcett, M and Finlay, L and Guy, H and Hays, C and Hogg, V and Horsley, E and Hubbuck, C and Pringle, C and Stevenson, C and Storey, K and Thompson, T and Woodward, S and Banerjee, A and Allcock, C and Merotra, S and Douglass, C and Campbell, E and Jarapa, R and Johnes, M and Keaveney, C and Marsden, T and Naing, Z and Perez, J and Shaw, K and Black, T and Anthony, A and Clarke, C and Paterson, J and Deighton, K and Temlett, E and Blank, C and Doyle, C and Duty, S and Gill, K and Harkness, K and Kamara, C and Richards, E and Elfandi, K and Guyler, P and Harman, P and Khuoge, C and Kunhunny, S and Tysoe, S and Moynihan, B and Adedoyin, T and Chopra, N and Dayal, N and Ghatala, R and Jeyaraj, N and Jones, I and Kennedy, F and Kerin, L and Khanom, N and Lewis, S and Maheswaran, S and Montague, L and Niemierko, M and O'Reilly, J and Trippier, S and Watson, F and Wilkinson, P and Young, E and Dizayee, K and Cochrane, H and O'Connell, J and Mokoena, L and Osborne, E and Nair, A and Greig, J and Jenkins, C and Powell, J and Price, F and Chowdhury, M and Brixey, S and Hunt, L and Rands, N and Rose, G and Stoddart, S and Srinivasan, M and Motherwell, N and Shekhar, R and Fuller, T and Lankester, A and Lingwood, P and Rankin, C and Webb, H and Jupp, B and Bell, J and Hann, G and Longland, B and Ovington, C and Bhaskaran, B and Ayres, G and Bailey, C and Bearne, H and Buxton, J and Fitzell, P and Hilaire, C and Kelly, D and Szabo, S and Tomlin, D and Gamble, E and Charles, B and Kumar, R and Fluskey, T and Mellor, Z and Peters, J and Sutton, V and Kenton, A and Martin, I and Nyabadza, S and Ghosh, S and Henry, M and Kumar, B and Bruce, D and Ambulo, C and Crawford, S and Nozedar, T and Platton, M and Cvoro, V and Couser, M and McCormick, K and Wilkinson, D and Javaid, K and Hurdowar, S and Attygalle, T and Sundayi, S and Orugun, O and Crowther, H and Jolly, R and Poultney, U and Azim, A and Krasinska-Chavez, M and White, J and Sengupta, N and Margalef, J and Metiu, M G and Meenakshisundaram, S and Dealing, S and Hargroves, D and Beranova, E and Cowie, L and Rudenko, H and Thomson, A and Verrion, A and Rashed, K and Board, S and Buckley, C and Hayward, D and Jenkins, K and Keeling, E and Rowland-Axe, R and Vickers, C and Wood, D and Lehman, A and Erande, R and Patel, M and Russell, H and Rehman, H and Forrest, D and Farren, P} }