Low-Molecular-Weight and Unfractionated Heparin for Prevention of Venous Thromboembolism in Neurosurgery: A Meta-analysis

BACKGROUND: Venous thromboembolism is a common, life-threatening complication in neurosurgery, but prophylaxis with anticoagulant agents has not gained wide acceptance because of concern about intracranial bleeding. We performed a meta-analysis of controlled randomized trials on the efficacy and safety of heparin in the prophylaxis of venous thromboembolism in neurosurgery. OBJECTIVE: To review the clinical benefit of prophylaxis of venous thromboembolism with heparin in the controversial setting of neurosurgery. METHODS: Relevant trials evaluating heparin for prophylaxis of venous thromboembolism in neurosurgery were identified by a MEDLINE search, scan of meeting abstracts, and scrutiny of the references of original articles and reviews. Four controlled randomized studies, 3 of which involved low-molecular-weight heparin, were included in the analysis, and 4 uncontrolled studies are commented on in the article. The outcome measure (observed minus expected number of events) and its variance were calculated for each single trial and then summed. Two-tailed P values and 95% confidence intervals (CIs) were calculated. Efficacy was assessed per protocol and safety by intention-to-treat analysis. The homogeneity of the studies was tested with the chi(2) statistic. The results were also expressed as number needed for 1 extra event. RESULTS: A total of 187 thromboembolic events were recorded in 827 patients (22.6%). Heparin prophylaxis resulted in a 45% relative risk reduction of venous thromboembolic events (odds ratio [OR], 0.48; 95% CI, 0.35-0.66; P<. 001). Nineteen major bleedings were recorded in 1022 patients. None were fatal. Heparin treatment resulted in a 71% relative risk increase of major bleeding (OR, 1.72; 95% CI, 0.69-4.27; P =.24). The number needed to treat was 7.7 for venous thromboembolism and 16 for proximal deep vein thrombosis. The number needed to harm was 102 (115 for low-molecular-weight heparin). CONCLUSIONS: Low-molecular-weight and unfractionated heparin have been shown to be effective for prophylaxis of venous thromboembolism in elective neurosurgery without excessive bleeding risk.