Efficacy and Safety of Anticoagulant Therapy for the Treatment of Acute Cancer-Associated Thrombosis: A Systematic Review and Meta-Analysis

Background: Current clinical practice guidelines all recommend the use of therapeutic doses of low molecular weight heparins (LMWH) for the initial and long-term treatment of cancer-related thrombosis. The use of vitamin-K antagonists (VKA) is acceptable if LMWH is not available. Direct oral anticoagulants (DOACs) have been shown to be comparable to conventional therapy for the acute treatment of VTE but their efficacy and safety in cancer patients remains uncertain. Methods: A systematic literature search strategy was conducted using MEDLINE, EMBASE, and the EBM reviews. Randomized controlled trials (RCTs) reporting rates of recurrent VTE and major bleeding in cancer patients were included. Relative risks (RR) (95% confidence intervals (CI)) for these outcomes were generated. Results: A total of 9 RCTs (2310 patients) were included in our analysis. In comparison to VKA, LMWH showed a significant reduction in recurrent VTE events (RR: 0.52; 95% CI: 0.36 to 0.74) whereas DOACs did not (RR: 0.66; 95% CI: 0.39 to 1.11). LMWH was associated with a non significant increase in the risk of major bleeding (RR: 1.06; 95% CI: 0.5 to 2.23) whereas DOACs showed a non significant reduction (RR: 0.78; 95% CI: 0.42 to 1.44). Annualized risks of recurrent VTE and major bleeding among patients randomized to VKA were higher in the LMWH studies as compared to the studies assessing DOACs suggesting that a higher risk cancer population were enrolled in the LMWH studies. Conclusions: LMWH should be used for the treatment of acute cancer-associated thrombosis. The use DOACs cannot be supported until trials comparing them to LMWH are conducted. (C) 2014 Elsevier Ltd. All rights reserved.