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Meta-Analysis
. 2015 Mar 12;2015(3):CD000024.
doi: 10.1002/14651858.CD000024.pub4.

Anticoagulants for acute ischaemic stroke

Peter A G Sandercock  1 , Carl Counsell, Edward J Kane
Affiliations
Meta-Analysis

Anticoagulants for acute ischaemic stroke

Peter A G Sandercock et al. Cochrane Database Syst Rev. .

Update in

  • Anticoagulants for acute ischaemic stroke.
    Wang X, Ouyang M, Yang J, Song L, Yang M, Anderson CS. Wang X, et al. Cochrane Database Syst Rev. 2021 Oct 22;10(10):CD000024. doi: 10.1002/14651858.CD000024.pub5. Cochrane Database Syst Rev. 2021. PMID: 34676532 Free PMC article.

Abstract

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 methods: 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).

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.

PubMed Disclaimer

Conflict of interest statement

Dr Sandercock was the principal investigator of the International Stroke Trial and Dr Counsell was also on the Steering Committee of this trial (IST 1997). Edward Kane has no conflicts of interest to declare.

Figures

1
1
Study flow diagram for 2014 update
2
2
Death from all causes during the treatment period
3
3
Death from all causes during final follow up
4
4
Funnel plot of deep vein thrombosis during follow‐up showing asymmetry
1.1
1.1. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 1 Dead or dependent at end of follow up (if > 1 month).
1.2
1.2. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 2 Death from all causes during treatment period.
1.3
1.3. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 3 Death from all causes at final follow up (if > 1 month).
1.4
1.4. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 4 Deep vein thrombosis during treatment period.
1.5
1.5. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 5 Symptomatic pulmonary embolism during treatment period.
1.6
1.6. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 6 Recurrent ischaemic or unknown stroke during treatment period.
1.7
1.7. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 7 Symptomatic intracranial haemorrhage during treatment period.
1.8
1.8. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 8 Any recurrent stroke or symptomatic intracranial haemorrhage during treatment period or follow up (> 1 month).
1.9
1.9. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 9 Major extracranial haemorrhage during treatment period.
1.10
1.10. Analysis
Comparison 1 Anticoagulant versus control in acute presumed ischaemic stroke, Outcome 10 Subgroup analysis by anticoagulant dose: effect on death or dependency.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Bradshaw 1975 {published data only}
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