Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer

Background Compared to patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE). Objectives To compare the efficacy and safety of three types of parenteral anticoagulants for the initial treatment of VTE in patients with cancer. Search strategy A comprehensive search for studies of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science. Selection criteria Randomized clinical trials (RCTs) comparing low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux in patients with cancer and objectively confirmed VTE. Data collection and analysis Using a standardized data form, data was extracted in duplicate on methodological quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. Main results Of 3986 identified citations, 16 RCTs were eligible: 13 compared LMWH to UFH, two compared fondaparinux to heparin, and one compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow up with LMWH compared with UFH (relative risk (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodological quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of death (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63) or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin to tinzaparin did not find a statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73). Authors' conclusions LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient important outcomes will further inform the questions addressed in this review.