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

Most strokes are due to a sudden blockage of an artery in the brain (this type of stroke is called an ischaemic stroke). In most ischaemic strokes, the blockage is caused by a blood clot. In patients with an irregular heart rhythm (atrial fibrillation), anticoagulant drugs, such as warfarin, prevent such clots forming and prevent stroke. However, anticoagulant drugs may also cause bleeding in the brain and this harmful effect could outweigh any benefits in patients with a normal heart rhythm. This review identified 11 trials, involving 2487 participants who had had a stroke (and also had a normal heart rhythm), of anticoagulants to prevent further strokes. There was good evidence that anticoagulants could cause serious bleeding, and there was no evidence that, in such patients, anticoagulants were of benefit in the prevention of further strokes. Other trials have shown that, in a person with a normal heart rhythm who has had an ischaemic stroke, antiplatelet drugs such as aspirin are a safe and effective way to reduce the risk of further strokes and heart attacks.

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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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.

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