Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44448
Full metadata record
DC FieldValueLanguage
dc.contributor.authorBath, PM-
dc.contributor.authorWoodhouse, LJ-
dc.contributor.authorAppleton, JP-
dc.contributor.authorBeridze, M-
dc.contributor.authorChristensen, H-
dc.contributor.authorDineen, RA-
dc.contributor.authorFlaherty, K-
dc.contributor.authorDuley, L-
dc.contributor.authorEngland, TJ-
dc.contributor.authorHavard, D-
dc.contributor.authorHeptinstall, S-
dc.contributor.authorJames, M-
dc.contributor.authorKasonde, C-
dc.contributor.authorKrishnan, K-
dc.contributor.authorMarkus, HS-
dc.contributor.authorMontgomery, AA-
dc.contributor.authorPocock, S-
dc.contributor.authorRandall, M-
dc.contributor.authorRanta, A-
dc.contributor.authorRobinson, TG-
dc.contributor.authorScutt, P-
dc.contributor.authorVenables, GS-
dc.contributor.authorSprigg, N-
dc.date.accessioned2019-06-17T11:01:25Z-
dc.date.available2019-06-17T11:01:25Z-
dc.date.issued2018-09-
dc.identifier.citationHealth Technology Assessment, 2018, 22 (48), pp. 1-76en
dc.identifier.urihttp://hdl.handle.net/2381/44448-
dc.descriptionAnonymised data will be deposited with the Virtual International Stroke Trials Archive.108 All queries and data requests should be submitted to the corresponding author for consideration in the first instance.en
dc.description.abstractBACKGROUND: Two antiplatelet agents are better than one for preventing recurrent stroke after acute ischaemic stroke or transient ischaemic attack (TIA). Therefore, intensive treatment with three agents might be better still, providing it does not cause undue bleeding. OBJECTIVE: To compare the safety and efficacy of intensive therapy with guideline antiplatelet therapy for acute ischaemic stroke and TIA. DESIGN: International prospective randomised open-label blinded end-point parallel-group superiority clinical trial. SETTING: Acute hospitals at 106 sites in four countries. PARTICIPANTS: Patients > 50 years of age with acute non-cardioembolic ischaemic stroke or TIA within 48 hours of ictus (stroke). INTERVENTIONS: Participants were allocated at random by computer to 1 month of intensive (combined aspirin, clopidogrel and dipyridamole) or guideline (combined aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents, and followed for 90 days. MAIN OUTCOME MEASURES: The primary outcome was the incidence and severity of any recurrent stroke (ischaemic, haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days by blinded telephone follow-up. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included bleeding and its severity, death, myocardial infarction (MI), disability, mood, cognition and quality of life. RESULTS: The trial was stopped early on the recommendation of the Data Monitoring Committee after recruitment of 3096 participants (intensive, n = 1556; guideline, n = 1540) from 106 hospitals in four countries between April 2009 and March 2016. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy in 3070 (99.2%) participants with data [93 vs. 105 stroke/TIA events; adjusted common odds ratio 0.90, 95% confidence interval (CI) 0.67 to 1.20; p = 0.47]. Major (encompassing fatal) bleeding was increased with intensive as compared with guideline therapy [39 vs. 17 participants; adjusted hazard ratio (aHR) 2.23, 95% CI 1.25 to 3.96; p = 0.006]. There were no differences between the treatment groups in all-cause mortality, or the composite of death, stroke, MI and major bleeding (aHR 1.02, 95% CI 0.77 to 1.35; p = 0.88). LIMITATIONS: Patients and investigators were not blinded to treatment. The comparator group comprised two guideline strategies because of changes in national guidelines during the trial. The trial was stopped early, thereby reducing its statistical power. CONCLUSIONS: The use of three antiplatelet agents is associated with increased bleeding without any significant reduction in recurrence of stroke or TIA. FUTURE WORK: The safety and efficacy of dual antiplatelet therapy (combined aspirin and clopidogrel) versus aspirin remains to be defined. Further research is required on identifying individual patient response to antiplatelets, and the relationship between response and the subsequent risks of vascular recurrent events and bleeding complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47823388. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 48. See the NIHR Journal Library website for further project information. The Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) vanguard phase was funded by the British Heart Foundation (grant PG/08/083/25779, from 1 April 2009 to 30 September 2012) and indirect funding was provided by the Stroke Association through its funding of the Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK. There was no commercial support for the trial and antiplatelet drugs were sourced locally at each site. The trial was sponsored by the University of Nottingham.en
dc.description.sponsorshipWe thank the participants, investigators and research staff at the participating sites and members of the TSC and independent DMC for their involvement in, and support for, the study. We also thank the NIHR Stroke Research Network/Clinical Research Network (Stroke) for its support for recruitment in the UK, which would not have been possible otherwise.en
dc.language.isoenen
dc.publisherNIHR Journals Library-
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/30179153-
dc.rights© Queen’s Printer and Controller of HMSO 2018. This work was produced by Bath et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising.en
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectAspirinen
dc.subjectClopidogrelen
dc.subjectDipyridamoleen
dc.subjectDrug Therapy, Combinationen
dc.subjectFemaleen
dc.subjectHemorrhageen
dc.subjectHumansen
dc.subjectIschemic Attack, Transienten
dc.subjectLogistic Modelsen
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectPlatelet Aggregation Inhibitorsen
dc.subjectProspective Studiesen
dc.subjectQuality of Lifeen
dc.subjectRecurrenceen
dc.subjectResearch Designen
dc.subjectSeverity of Illness Indexen
dc.subjectStrokeen
dc.titleTriple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT.en
dc.typeJournal Articleen
dc.identifier.doi10.3310/hta22480-
dc.identifier.eissn2046-4924-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article;Multicenter Study;Randomized Controlled Trial;Research Support, Non-U.S. Gov't-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCESen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Cardiovascularen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Neuroscience & Behaviouren
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

Files in This Item:
File Description SizeFormat 
3021225.pdfPublished (publisher PDF)1.05 MBAdobe PDFView/Open


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.