Meta-Analyses of Randomised Controlled Trials (RCT) of Warfarin and Low Molecular Weight Heparin (LMWH) for the Prevention of Venous Thromboembolism (VTE) and Death in Cancer Patients.

VTE is a common clinical problem in cancer patients. Uncertainty remains as to whether prophylactic treatment of oral anticoagulants (mainly warfarin) or LMWHs, given by subcutaneous injection, is beneficial and practice varies widely. It has been proposed that anticoagulant therapy may also improve survival in cancer patients. The largest trial of VTE prophylaxis in cancer patients with central venous catheters (CVCs), WARP, has just been completed and showed no apparent benefit for low dose warfarin - among 811 patients randomised to low dose warfarin versus not, the VTE rate was 5% in both arms (odds ratio [OR]=1.04, 95% confidence interval [CI]=0.56–1.92, p=1.0) and mortality was not reduced (OR=1.02, CI=0.74–1.4, p=0.8) (Young et al., ASCO, 2005, LBA8004). This result needs to be put in the context of other RCTs of prophylaxis with anticoagulants, so we performed a meta-analysis to evaluate the effect of warfarin and LMWH on VTE rates and cancer mortality. Computerized searches for trials were performed, including MedLine, Embase, NCI trials register, ASCO and ASH meeting abstracts. Standard meta-analysis methods were used and the results presented as ORs and CIs, with heterogeneity of treatment effect between trials examined using tests for interaction. In 5 trials (n=1355 patients) of warfarin v. not, there was no clear evidence of a decrease in VTEs (OR=0.68, CI=0.46–1.01, p=0.06). An additional 3 trials (n=2034 for all 8 trials) had survival data and there was no clear evidence of a decrease in mortality (OR=0.88, CI=0.77–1.01, p=0.06). In 5 trials (n=793) of LMWH v. not, VTE rate was reduced (OR=0.53, CI=0.32–0.87, p=0.01). 6 trials (n=1295) contained survival data and mortality was reduced with LMWH (OR=0.79, CI=0.67–0.92, p=0.003). In 3 trials (n=985) of LMWH v. oral anti-coagulation (mainly with warfarin), VTE rates were lower with LMWH (OR=0.46, CI=0.32–0.67, p<0.0001) but no mortality benefit was observed (OR=0.89, CI=0.72–1.1, p=0.3). The results of these preliminary meta-analyses suggest that LMWH is the preferred form of prophylaxis for VTE in cancer patients and that overall, there may be an anti-tumour effect, leading to a survival benefit.