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A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility.

Sprigg N, Gray LJ, England T, Willmot MR, Zhao L, Sare GM, Bath PM - PLoS ONE (2008)

Bottom Line: Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention.The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01).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.

View Article: PubMed Central - PubMed

Affiliation: Stroke Trials Unit, Institute of Neuroscience, University of Nottingham, Nottinghamshire, United Kingdom.

ABSTRACT

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.

Trial registration: Controlled-Trials.com ISRCTN83673558.

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Related in: MedlinePlus

Flow of patients through trial.
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pone-0002852-g001: Flow of patients through trial.

Mentions: Seventeen patients were enrolled between 2002 and 2006 (figure 1). The trial was stopped prematurely following publication of the ESPRIT trial which confirmed ESPS II in showing that combined aspirin and dipyridamole is superior to aspirin alone in preventing recurrent stroke and other vascular events.[4], [5] Additionally, the UK National Institute of Clinical Excellence recommend this combination as first line therapy for patients with prior ischaemic cerebrovascular disease.[20] As such, we considered it unethical to continue randomising patients to receive mono-therapy with aspirin.


A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility.

Sprigg N, Gray LJ, England T, Willmot MR, Zhao L, Sare GM, Bath PM - PLoS ONE (2008)

Flow of patients through trial.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2481397&req=5

pone-0002852-g001: Flow of patients through trial.
Mentions: Seventeen patients were enrolled between 2002 and 2006 (figure 1). The trial was stopped prematurely following publication of the ESPRIT trial which confirmed ESPS II in showing that combined aspirin and dipyridamole is superior to aspirin alone in preventing recurrent stroke and other vascular events.[4], [5] Additionally, the UK National Institute of Clinical Excellence recommend this combination as first line therapy for patients with prior ischaemic cerebrovascular disease.[20] As such, we considered it unethical to continue randomising patients to receive mono-therapy with aspirin.

Bottom Line: Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention.The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01).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.

View Article: PubMed Central - PubMed

Affiliation: Stroke Trials Unit, Institute of Neuroscience, University of Nottingham, Nottinghamshire, United Kingdom.

ABSTRACT

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.

Trial registration: Controlled-Trials.com ISRCTN83673558.

Show MeSH
Related in: MedlinePlus