Anticoagulants for acute ischaemic stroke

Millions of people around the world have strokes every year. Most strokes take place when a blood clot blocks a blood vessel leading to the brain. Without a proper blood supply, the brain quickly suffers damage, which can be permanent. The damage from a stroke can cause arm or leg weakness, or difficulties with language or vision. Strokes are sometimes fatal, but will more often leave the survivor unable to do the things that they used to do. Because strokes are common and cause such damage, researchers are trying to find ways to get rid of the blood clot soon after the stroke happens. One way to do this is with blood thinning drugs called anticoagulants. If anticoagulants work, the bad effects of the stroke might be avoided. The main problem with anticoagulants is that they can cause bleeding, which can sometimes be very serious. This systematic review was designed to find out whether people treated with anticoagulants soon after having a stroke got better or not, and whether they had problems with bleeding. There is a lot of information in this systematic review - 23,748 people with stroke have been involved in 24 included randomised trials to answer this question. People treated with anticoagulants did not have less long-term disability, and experienced more bleeding. Anticoagulant treated patients had less chance of developing blood clots in their legs and in their lungs following their stroke, but these benefits were offset by the increased number of bleeds. This review did not provide any evidence that the early use of anticoagulants is of overall benefit to people with strokes caused by blood clots. More research is needed to find out if there are ways to select the people with stroke who will benefit from anticoagulants without suffering the bleeding complications.

Authors' conclusions: 

Since the last version of the review, no new relevant studies have been published and so there is no additional information to change the conclusions. Early anticoagulant therapy is not associated with net short- or long-term benefit in people with acute ischaemic stroke. 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 of the currently available anticoagulants in acute ischaemic stroke.

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Background: 

Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Clot prevention with anticoagulants might improve outcomes if bleeding risks are low. This is an update of a Cochrane review first published in 1995, with recent updates in 2004 and 2008.

Objectives: 

To assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) in people with acute presumed or confirmed ischaemic stroke.

Search strategy: 

We searched the Cochrane Stroke Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR), the Database of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA) (The Cochrane Library 2014 Issue 6), MEDLINE (2008 to June 2014) and EMBASE (2008 to June 2014). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies.

Selection criteria: 

Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people 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: 

We included 24 trials involving 23,748 participants. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence relates to the effects of anticoagulant therapy initiated within the first 48 hours of onset. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy started within the first 14 days of stroke onset 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 early anticoagulation 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 early 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, early anticoagulation reduced the frequency of symptomatic 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).

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