Anticoagulants for Acute Ischemic Stroke
Graeme J. Hankey MD, FRCP Section Editor:
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.
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.
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).
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.
Data Collection and Analysis
Two review authors independently selected trials for inclusion, assessed trial quality, and extracted the data.
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).
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.
- Received September 21, 2008.
- Accepted October 1, 2008.