A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility

Background: Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. Methodology/Principal Findings: A randomised,...

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Main Authors: Sprigg, Nikola, Gray, Laura J., England, Timothy J., Wilmot, Marc R., Zhao, Lian, Sare, Gillian M., Bath, Philip M.W.
Format: Article
Published: 2008
Online Access:https://eprints.nottingham.ac.uk/948/
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author Sprigg, Nikola
Gray, Laura J.
England, Timothy J.
Wilmot, Marc R.
Zhao, Lian
Sare, Gillian M.
Bath, Philip M.W.
author_facet Sprigg, Nikola
Gray, Laura J.
England, Timothy J.
Wilmot, Marc R.
Zhao, Lian
Sare, Gillian M.
Bath, Philip M.W.
author_sort Sprigg, Nikola
building Nottingham Research Data Repository
collection Online Access
description Background: Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. Methodology/Principal Findings: A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p,0.01). Conclusions/Significance: Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy.
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spelling nottingham-9482020-05-04T20:27:57Z https://eprints.nottingham.ac.uk/948/ A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility Sprigg, Nikola Gray, Laura J. England, Timothy J. Wilmot, Marc R. Zhao, Lian Sare, Gillian M. Bath, Philip M.W. Background: Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. Methodology/Principal Findings: A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p,0.01). Conclusions/Significance: Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy. 2008 Article PeerReviewed Sprigg, Nikola, Gray, Laura J., England, Timothy J., Wilmot, Marc R., Zhao, Lian, Sare, Gillian M. and Bath, Philip M.W. (2008) A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility. PLoS One, 3 (8).
spellingShingle Sprigg, Nikola
Gray, Laura J.
England, Timothy J.
Wilmot, Marc R.
Zhao, Lian
Sare, Gillian M.
Bath, Philip M.W.
A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
title A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
title_full A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
title_fullStr A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
title_full_unstemmed A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
title_short A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
title_sort randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility
url https://eprints.nottingham.ac.uk/948/