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 (especially myocardial infarction and recurrent stroke) 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
The objective of this review was 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. We contacted companies marketing anticoagulant agents. The most recent search for this review was carried out in August 2002.


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 reviewers independently selected trials for inclusion, assessed trial quality and extracted the data.


RESULTS
Eleven trials involving 2487 patients were included. The quality of the 9 trials which predated routine computerised tomography 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 0.83, 95% confidence interval [CI] 0.52 to 1.34) or of 'non-fatal stroke, myocardial infarction, or vascular death' (four trials, odds ratio 0.96, 95% CI 0.68-1.37). Death from any cause (odds ratio 0.95, 95% CI 0.73 to 1.24) and death from vascular causes (odds ratio 0.86, 95% CI 0.66 to 1.13) were not significantly different between treatment and control. The inclusion of two recent completed trials did not alter these conclusions. There was no evidence of an effect of anticoagulant therapy on the risk of recurrent ischaemic stroke (odds ratio 0.85, 95% CI 0.66 to 1.09). However, anticoagulants increased fatal intracranial haemorrhage (odds ratio 2.54, 95% CI 1.19 to 5.45), and major extracranial haemorrhage (odds ratio 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.
Sandercock
P
P
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, UK, EH4 2XU. pags@skull.dcn.ed.ac.uk
Mielke
O
O
Liu
M
M
Counsell
C
C
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