Stroke. 2009;40:e483-e484
Published online before print May 21, 2009,
doi: 10.1161/STROKEAHA.108.538157
(Stroke. 2009;40:e483.)
© 2009 American Heart Association, Inc.
Anticoagulants for Acute Ischemic Stroke
Peter Sandercock, DM, FRCPE;
Carl Counsell, MRCP, MSc, MD
Ayeesha K. Kamal, MBBS, AKU
From the Department of Clinical Neurosciences (P.S.), University of Edinburgh, Edinburgh, UK; the Division of Applied Health Sciences (C.C.), University of Aberdeen, Aberdeen, UK; and the Department of Neurology (A.K.K.), The Aga Khan University Hospital, Karachi, Pakistan.
Correspondence to Peter Sandercock, DM, FRCPE, Professor of Medical Neurology, Department of Clinical Neurosciences, Western General Hospital, Edinburgh, EH4 2XU, UK. E-mail Peter.sandercock{at}ed.ac.uk
Graeme J. Hankey MD, FRCP Section Editor:
Key Words: anticoagulants • ischemic stroke • systematic review
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Introduction
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Anticoagulants could be of net benefit in patients with acute
ischemic stroke if they reduce early recurrence of ischemic
stroke and prevent venous thromboembolism without causing an
excessive risk of intra- and extracranial bleeding. This review
has been continually updated since it was first published in
1995.
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Objective
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The objective of this study was to assess the effects of anticoagulant
therapy compared with control in the early treatment of patients
with acute ischemic stroke.
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Search Methods
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To update a previous comprehensive search, we searched the Cochrane
Stroke Group Trials Register (last searched October 2, 2007)
and 2 Internet clinical trials registries for relevant ongoing
studies (last searched October 2007).
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Selection Criteria
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We selected randomized trials comparing early anticoagulant
therapy (started within 2 weeks of stroke onset) with control
in patients with acute presumed or confirmed ischemic stroke.
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Data Collection and Analysis
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Two review authors independently selected trials for inclusion,
assessed trial quality, and extracted the data.
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Results
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Twenty-four trials involving 23 748 participants were included.
The anticoagulants tested were standard unfractionated heparin,
low-molecular-weight heparins, heparinoids, oral anticoagulants,
and thrombin inhibitors. For the analysis of the primary outcome,
all of the data related to the initiation of anticoagulants
within 48 hours of onset, and 89% of the evidence related to
unfractionated heparin. Based on 11 trials (22 776 participants),
there was no evidence that anticoagulant therapy reduced the
odds of death from all causes (OR, 1.05; 95% CI, 0.98 to 1.12)
at the end of follow up. Similarly, based on 8 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;
Figure). Although anticoagulant
therapy was associated with fewer recurrent ischemic strokes
(OR, 0.76; 95% CI, 0.65 to 0.88), it was also associated with
an increase in symptomatic intracranial hemorrhages (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 hemorrhages
(OR, 2.99; 95% CI, 2.24 to 3.99).
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Figure. Systematic review of randomized trials comparing anticoagulants with control in people with acute ischemic stroke. Results are expressed as Peto OR and 95% CI with fixed-effects model. OR <1 suggests anticoagulants were superior to control. Effects on number of patients with poor outcome (dead or dependent in activities of daily living) were at the end of scheduled trial follow-up. (From Sandercock, Counsell C, Kamal A. Anticoagulants for acute ischemic stroke. Cochrane Database Syst Rev. 2008;4:CD000024. Reproduced with permission from John Wiley & Sons, Ltd.)
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Conclusions
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Addition of the 2 new studies identified since the last update
did not change the conclusions. In patients with acute ischemic
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.
Implications for Practice
The data do not support the routine use of any of the currently available anticoagulants in acute ischemic stroke. The review did not identify any category of patient in which there was clear net benefit. Clinicians who feel compelled to use immediate anticoagulants for specific categories of patients after acute ischemic stroke should weigh any potential theoretical benefits with the known risk of bleeding. Aspirin is an effective antithrombotic alternative to anticoagulation, which is safe when used in the acute phase of ischemic stroke.
Implications for Research
This review has not provided reliable evidence on a number of important categories of patient with acute cerebrovascular disease who might plausibly derive net benefit from immediate anticoagulation; very recent transient ischemic attacks (within hours or days of onset), crescendo transient ischemic attacks, and progressing ischemic stroke are a few examples. Further trials targeted at these groups (perhaps with new agents) may be warranted. This review has not provided clear evidence about the optimum antithrombotic regimen for the prevention of deep vein thrombosis and pulmonary embolism in patients with stroke. Aspirin alone, low-dose subcutaneous heparin, and the use of graded compression stockings are all promising possibilities, but a very large-scale randomized trial with several 10s of thousands of patients would be required to determine which (or which combination) has the most favorable balance of risk and benefit (if overall functional outcome is the primary outcome).
Reference to full review: Sandercock P, Counsell C, Kamal A. Anticoagulants for acute ischemic stroke. Cochrane Database Syst Rev. 2008;4:CD000024. Cochrane reviews are regularly updated. Please refer to the Cochrane Library for the most up-to-date version of this review.
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Acknowledgments
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Disclosures
None.
Received September 21, 2008;
accepted October 1, 2008.
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Introduction
Objective