Anticoagulation for Cerebral Venous Sinus Thrombosis
Treatment of cerebral venous thrombosis with anticoagulants may prevent new venous infarcts, neurological deterioration, and pulmonary embolism but may also promote hemorrhages.
Materials and Methods
The objective of the study was to assess the efficacy and safety of anticoagulant therapy in patients with radiologically confirmed cerebral venous thrombosis. This is an update of the 2002 version of the Cochrane Review on this topic.1
We searched the Cochrane Stroke Group Trials Register (last searched August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010), and the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trial registers and reference lists of relevant articles and contacted the authors.
Selection criteria included nonconfounded randomized controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral venous thrombosis. The diagnosis had to be confirmed by MR venography, CT venography, or conventional angiography.
Data Collection and Analysis
Two review authors independently extracted outcomes for each of the 2 treatment groups. The outcome data for each patient were analyzed in the treatment group to which the patient was originally allocated (intention-to-treat analysis). We calculated a weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction).
We included 2 small trials involving 79 patients. One trial (20 patients) examined the efficacy of intravenous adjusted-dose unfractionated heparin. The other trial (59 patients) examined high-dose, body weight-adjusted, subcutaneous, low-molecular-weight heparin (nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95% CI, 0.08–1.21) and relative risk of death or dependency of 0.46 (95% CI, 0.16–1.31; Figure). The absolute reduction in the risk of death or dependency was 13% (95% CI, 30% to −3%). No new symptomatic intracerebral hemorrhages were observed. One major gastrointestinal hemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (1 fatal). We did not identify any randomized trial that included pediatric patients.
Two trials were excluded. One study has been published only as an abstract in 1997, and another trial did not meet our inclusion criterion of diagnostic confirmation; the diagnosis in this study was based on CT without venography. One trial that compared unfractionated with low-molecular-weight heparin is awaiting assessment because the study thus far has been published as an abstract only (2006).
Implications for Research
Although the estimated pooled risk reductions did not reach statistical significance, patients and doctors may be reluctant to embark on a new trial in adult patients that includes a placebo group. International guidelines recommend the use of heparin as the primary treatment of adult patients with cerebral venous thrombosis, regardless of the presence of baseline intracerebral hemorrhagic lesions, and most physicians follow this recommendation. In pediatric patients, especially neonates, a randomized trial seems warranted. Large consecutive cohort studies have helped to identify subgroups of patients with a poor prognosis. A randomized trial testing endovascular treatment in such patients is currently being undertaken (www.to-act-trial.org).
Based on the limited evidence available, anticoagulant treatment for cerebral venous thrombosis appears to be safe and is associated with a potentially important reduction in the risk of death or dependency that did not reach statistical significance.
Sources of Funding
Dr Coutinho is supported by “The Netherlands Organisation for Scientific Research” (NWO), grant number 021.001.045.
This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2011, Issue 8. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the review.
- Received December 14, 2011.
- Accepted December 19, 2011.
- © 2012 American Heart Association, Inc.