Treatment of cancer-associated venous thromboembolism by new oral anticoagulants: a meta-analysis

Abstract

Background: The efficacy and safety of newer oral anticoagulants (NOAs) compared to vitamin K antagonist (VKA) in preventing the recurrence of venous thromboembolism (VTE) is well documented. However, it still needs to be determined whether this pattern holds when compared to the combination of low-molecular-weight heparin (LMWH) and VKA in patients with VTE and malignancy. Methods: For this analysis, the authors searched available databases for randomized controlled trials (RCTs) comparing the NOAs with standard treatment (combination of LMWH and VKA) in patients with VTE and those comparing NOAs with LMWH only for prevention of VTE. All these RCTs included small proportion of patients with cancer. The authors then assessed the pooled treatment effects of VTE recurrence, as well as major and non-major clinically relevant bleeding in the two groups. Results: Twelve studies met our inclusion criteria, yielding 2,054 patients. Five studies with rivaroxaban, three each with dabigatran and apixaban, and one with edoxaban compared NOAs with standard treatment. There was a non-significant reduction in VTE recurrence by the NOAs (3.95%) compared to standard treatment (5.62%) [risk ratio (RR) =0.68; 95% confidence interval (CI) =0.42–1.10; P=0.12]. The major bleeding rate with NOAs was (2.62%) compared to the corresponding rate for standard treatment (3.75%) (RR =0.66; 95% CI =0.36–1.20; P=0.17). The non-major clinically relevant bleeding rate with NOAs was (12.82%) compared to the rate for standard treatment (15.52%) (RR =0.85; 95% CI =0.65–1.10; P= 0.22). However, compared to LMWH only, both higher major (RR =2.18; 95% CI =0.32–14.80; P=0.42) and non-major clinically relevant (RR =2.39; 95% CI =0.75–7.56; P=0.14) bleeding rates were noted with NOAs use in acutely-ill hospitalized patients. Conclusions: NOAs seem to be comparable to standard treatment in both their efficacy and safety in patients with VTE and malignancy. However, increased rates of bleeding were observed with their use compared to LMWH use in acutely-ill hospitalized patients.