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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

Bath, Philip M.W.; Woodhouse, Lisa J.; Appleton, Jason P.; Beridze, M.; Christensen, Hanne; Dineen, Robert A.; Duley, Lelia; England, Timothy J.; Flaherty, Katie; Havard, Diane; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, H.S.; Montgomery, Alan A.; Pocock, Stuart J.; Randall, Marc; Ranta, A.; Robinson, Thompson G.; Scutt, Polly; Venables, Graham S.; Sprigg, Nikola

Authors

Philip M.W. Bath

Lisa J. Woodhouse

Jason P. Appleton

M. Beridze

Hanne Christensen

Robert A. Dineen

Lelia Duley

Timothy J. England

Katie Flaherty

Diane Havard

Stan Heptinstall stan.heptinstall@nottingham.ac.uk

Marilyn James

Kailash Krishnan kailash.krishnan@nottingham.ac.uk

H.S. Markus

Alan A. Montgomery

Stuart J. Pocock

Marc Randall

A. Ranta

Thompson G. Robinson

Polly Scutt

Graham S. Venables

Nikola Sprigg

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

Journal Article Type Article
Publication Date Mar 3, 2018
Journal Lancet
Print ISSN 0140-6736
Electronic ISSN 1474-547X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 391
Issue 10123
DOI https://doi.org/10.1016/S0140-6736%2817%2932849-0
Publisher URL http://www.sciencedirect.com/science/article/pii/S0140673617328490
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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