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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

Frequencies of adverse events in aspirin and triple therapy groups.
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pone-0002852-g002: Frequencies of adverse events in aspirin and triple therapy groups.

Mentions: One patient died in the triple therapy group of acute myeloid leukaemia; no patients died in the aspirin group. When bleeding events were analysed as ordinal data (no bleed, minor bleed, major bleed)[19], significantly increased rates were seen in the triple therapy group (p<0.01). Similarly, there was a significant increase in the number and severity of adverse events (ordered as no event, adverse event, non-fatal serious adverse event, death) in the triple group (p<0.01) (table 2 and figure 2). Only one of the SAEs was thought to be related to treatment. There was a non-significant difference in efficacy between treatment groups (pā€Š=ā€Š0.53); one recurrent stroke (non-disabling) occurred in a patient randomised to triple therapy who was noncompliant of all three antiplatelet agents.


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)

Frequencies of adverse events in aspirin and triple therapy groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0002852-g002: Frequencies of adverse events in aspirin and triple therapy groups.
Mentions: One patient died in the triple therapy group of acute myeloid leukaemia; no patients died in the aspirin group. When bleeding events were analysed as ordinal data (no bleed, minor bleed, major bleed)[19], significantly increased rates were seen in the triple therapy group (p<0.01). Similarly, there was a significant increase in the number and severity of adverse events (ordered as no event, adverse event, non-fatal serious adverse event, death) in the triple group (p<0.01) (table 2 and figure 2). Only one of the SAEs was thought to be related to treatment. There was a non-significant difference in efficacy between treatment groups (pā€Š=ā€Š0.53); one recurrent stroke (non-disabling) occurred in a patient randomised to triple therapy who was noncompliant of all three antiplatelet agents.

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