Low-Molecular-Weight Heparins or Heparinoids Versus Standard Unfractionated Heparin for Acute Ischemic Stroke
Low-molecular-weight heparins (LMWHs) and heparinoids are anticoagulants that may be associated with lower risks of hemorrhage and more powerful antithrombotic effects than standard unfractionated heparin (UFH).
The objective of this review was to compare the effects of LMWHs or heparinoids with those of UFH in people with acute, confirmed, or presumed ischemic stroke.
We searched the Cochrane Stroke Group trials register (last searched November 2003). In addition, we searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2003, Issue 4), MEDLINE (1966 to October 2003), and EMBASE (1980 to October 2003).
Randomized trials comparing heparinoids or LMWHs with standard UFH in people with acute ischemic stroke. Only trials where treatment was started within 14 days of stroke onset were included.
Data Collection and Analysis
Two reviewers independently selected studies for inclusion, assessed trial quality, and extracted the data.
Six trials involving 740 people were included. Four trials compared a heparinoid (danaparoid), 1 trial compared a LMWH (enoxaparin), and 1 trial compared an unspecified LMWH with standard UFH. Allocation a to LMWH or heparinoid was associated with a significant reduction in the odds of deep vein thrombosis (Peto odds ratio, 0.52; 95% CI, 0.56 to 0.79). However, the number of more major events (pulmonary embolism [PE], death, intracranial, or extracranial hemorrhage) was too small to provide a reliable estimate of more important benefits and risks. No information was reported for recurrent stroke or functional outcome.
Treatment with a LMWH or heparinoid after acute ischemic stroke appears to decrease the occurrence of deep vein thrombosis compared with standard UFH, but there were too few events to provide reliable information on their effects on other important outcomes, including death, PE, or intracranial hemorrhage (Figure).
Implications for Practice
For clinicians who wish to use some form of anticoagulant regimen in selected patients with acute ischemic stroke, despite the lack of evidence of overall benefit from routine anticoagulants in patients with acute ischemic stroke: (1) the criteria to identify those few patients who might benefit from the UFH, LMWH, or heparinoid regimens tested in these trials have not been defined; (2) LMWH and heparinoids appear to be more effective at preventing deep venous thrombosis (and possibly also PE) than UFH. However, their safety, compared with UFH, has not reliably been established in stroke patients.
Implications for Research
Further very-large-scale trials may be worthwhile comparing: (1) “Aspirin alone” with “aspirin plus low dose LMWH (or heparinoid)” in individuals at particularly high risk of deep venous thrombosis and PE; (2) “a more aggressive LMWH (or heparinoid) regimen” with “UFH” and with “aspirin only” in certain categories of patients, eg, those with a cardiac source of emboli. These trials should measure disability and recurrent stroke as well as venous thromboembolism and major hemorrhages.
Note: The full text of this review is available in the Cochrane Library (for subscribers http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD000119/frame.html). The full article should be cited as: Sandercock P, Counsell C, Stobbs SL. Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischemic stroke. Cochrane Database Syst Rev. 2005. Issue 2.
- Received May 6, 2005.
- Accepted May 18, 2005.