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


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


METHODS
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.


METHODS
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.


METHODS
Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data.


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.


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.
Division of Clinical Neurosciences, University of Edinburgh, Neurosciences Trials Unit, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh, UK, EH4 2XU. peter.sandercock@ed.ac.uk
Peter A G
PA
Sandercock
Lorna M
LM
Gibson
Ming
M
Liu
D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control
D000925:Anticoagulants