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Review
. 2009 Apr 15;2009(2):CD000248.
doi: 10.1002/14651858.CD000248.pub2.

Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack

Peter A G Sandercock  1 , Lorna M Gibson, Ming Liu
Affiliations
Review

Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack

Peter A G Sandercock et al. Cochrane Database Syst Rev. .

Abstract

Background: After a first ischaemic stroke, further vascular events due to thromboembolism are common and often fatal. Anticoagulants could potentially reduce the risk of such events, but any benefits could be offset by an increased risk of fatal or disabling haemorrhages.

Objectives: To assess the effect of prolonged anticoagulant therapy compared with placebo or open control following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack.

Search strategy: We searched the Cochrane Stroke Group Trials Register in May 2008. In June 2008 we searched three online trial registers, used Web of Science Cited Reference Search to identify new citations of previously included studies, contacted a pharmaceutical company, and also contacted authors for additional information on included trials.

Selection criteria: Randomised and quasi-randomised trials comparing at least one month of anticoagulant therapy with control in people with previous, presumed non-cardioembolic, ischaemic stroke or transient ischaemic attack.

Data collection and analysis: Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data.

Main results: Eleven trials involving 2487 participants were included. The quality of the nine trials which predated routine computerised tomography (CT) scanning and the use of the International Normalised Ratio to monitor anticoagulation was poor. There was no evidence of an effect of anticoagulant therapy on either the odds of death or dependency (two trials, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.52 to 1.34) or of 'non-fatal stroke, myocardial infarction, or vascular death' (four trials, OR 0.96, 95% CI 0.68 to 1.37). Death from any cause (OR 0.95, 95% CI 0.73 to 1.24) and death from vascular causes (OR 0.86, 95% CI 0.66 to 1.13) were not significantly different between treatment and control. The inclusion of two recently completed trials did not alter these conclusions. There was no evidence of an effect of anticoagulant therapy on the risk of recurrent ischaemic stroke (OR 0.85, 95% CI 0.66 to 1.09). However, anticoagulants increased fatal intracranial haemorrhage (OR 2.54, 95% CI 1.19 to 5.45), and major extracranial haemorrhage (OR 3.43, 95% CI 1.94 to 6.08). This is equivalent to anticoagulant therapy causing about 11 additional fatal intracranial haemorrhages and 25 additional major extracranial haemorrhages per year for every 1000 patients given anticoagulant therapy.

Authors' conclusions: Compared with control, there was no evidence of benefit from long-term anticoagulant therapy in people with presumed non-cardioembolic ischaemic stroke or transient ischaemic attack, but there was a significant bleeding risk.

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Conflict of interest statement

Peter Sandercock was the principal investigator of the International Stroke Trial and Dr Counsell was also on the Steering Committee of this trial. Peter Sandercock has received, from a variety of manufacturers of antiplatelet and anticoagulant drugs (Sanofi, Bristol Meyer Squibb, Sanofi‐Synthelabo, Organon, Boehringer Ingelheim, Janssen): lecture fees and travel expenses for lectures delivered at conferences: consultancy fees; he has in the past received research grants from Glaxo‐Wellcome and Boehringer Ingelheim; the drug supply for the start‐up phase of the IST‐3 trial was donated to his department by Boehringer Ingelheim; he does not have any continuing contractual consultancy arrangements with any company, or any current research grants from any company, nor does he hold stock (or hold any other financial interests) in any pharmaceutical company.

Figures

1.1
1.1. Analysis
Comparison 1 Anticoagulant versus control, Outcome 1 Death or dependency at end of follow up.
1.2
1.2. Analysis
Comparison 1 Anticoagulant versus control, Outcome 2 Non‐fatal stroke, myocardial infarction or vascular death during follow up.
1.3
1.3. Analysis
Comparison 1 Anticoagulant versus control, Outcome 3 Deaths from any cause during follow up.
1.4
1.4. Analysis
Comparison 1 Anticoagulant versus control, Outcome 4 Vascular deaths during follow up.
1.5
1.5. Analysis
Comparison 1 Anticoagulant versus control, Outcome 5 Recurrent ischaemic/unknown stroke during follow up.
1.6
1.6. Analysis
Comparison 1 Anticoagulant versus control, Outcome 6 Symptomatic intracranial haemorrhage during follow up.
1.7
1.7. Analysis
Comparison 1 Anticoagulant versus control, Outcome 7 Any recurrent stroke or symptomatic intracranial haemorrhage during follow up.
1.8
1.8. Analysis
Comparison 1 Anticoagulant versus control, Outcome 8 Major extracranial haemorrhage during follow up.
1.9
1.9. Analysis
Comparison 1 Anticoagulant versus control, Outcome 9 Myocardial infarction during follow up.
1.10
1.10. Analysis
Comparison 1 Anticoagulant versus control, Outcome 10 Other embolic events during follow up.
1.11
1.11. Analysis
Comparison 1 Anticoagulant versus control, Outcome 11 Non‐fatal stroke/intracranial haemorrhage or vascular death during follow up.
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MeSH terms