Anticoagulants for acute ischaemic stroke

Background Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulants might improve outcome if bleeding risks were low. This is an update of a Cochrane review first published in 1995, and previously updated in 2004. Objectives To assess the effect of anticoagulant therapy versus control in the early treatment (less than 14 days) of patients with acute ischaemic stroke. Search strategy We searched the Cochrane Stroke Group Trials Register (last searched 2 October 2007), and two Internet clinical trials registries for relevant ongoing studies (last searched October 2007). Selection criteria Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. Data collection and analysis Two review authors independently selected trials for inclusion, assessed trial quality, and extracted the data. Main results Twenty-four trials involving 23,748 participants were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow up. Similarly, based on eight trials (22,125 participants), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow up (OR 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, anticoagulants reduced the frequency of pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99). Authors’ conclusions Since the last version of the review, neither of the two new relevant studies have provided additional information to change the conclusions. In patients with acute ischaemic stroke, immediate anticoagulant therapy is not associated with net short or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any the currently available anticoagulants in acute ischaemic stroke.