Efficacy of Low-molecular-weight-heparin versus Vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: A systematic review of randomized controlled trials

Background: Patients with malignancy have a 4-fold increase in the risk of developing a venous thrombosis and a 3-fold increase in risk of bleeding. Both low-molecular-weight-heparin (LMWH) and vitamin K antagonists (VKA) have been used for treatment of cancer-associated thrombosis. However, the best anticoagulation approach remains a matter of debate. Objective: In adult patients with cancer and an acute venous thromboembolic event we sought to determine the rates of recurrent venous thromboembolism (VTE) and major hemorrhage when treated with prolonged LMWH therapy compared to vitamin-K antagonists. Patients/Methods: A systematic literature search strategy was used to identify potential trials on MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Medline in-process using an OVID interface. Risk assessment of bias of randomized controlled trials (RCTs) was performed according to the Cochrane Collaboration-Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome measure was symptomatic VTE recurrence rate during the anticoagulation period. Relative risk (RR) was used as the primary measurement with 95% confidence intervals (CIs). Pooled measurements were calculated using random-effects and fixed-effects model. Results: Five articles met our inclusion criteria. All compared LMWH and VKA for secondary prevention of VTE. The pooled RR of VTE recurrence was 0.53 (95% Cl: 0.36-0.76; p = 0.007). The pooled RR of major bleeding was 0.98 (95% CI: 0.49-1.93, p = 0.95). Minor bleeding events and all cause mortality were similar between the 2 intervention arms. Conclusions: The results of our review suggest that the long term use of LMWH after the acute first week of treatment is superior to VKAs for secondary prevention of venous thromboembolism in adult patients with cancer. (C) 2008 Elsevier Ltd. All rights reserved.