Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials

Ruchi Desai,Damian Laber,Michael Jaglal,Rahul Mhaskar,Gautam Krishna Koipallil,Nathan Visweshwar,Nelson Thomas,Ankita Patel

doi:10.1038/s41598-020-75863-3

Abstract

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51–0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40–0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44–1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78–2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13–2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10–2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

Highlights

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT)
The efficacy results of our meta-analysis indicate that DOACs are superior to VKA or LMWH for secondary prevention of venous thromboembolism (VTE) in patients with CAT
The safety results of our meta-analysis indicate no difference in major bleeding (MB), clinically relevant non-major bleeding (CRNMB), or all bleeding risk with DOACs overall, but note risk of CNRMB and all bleeding without increased MB risk compared to LMWH

Summary

Introduction

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). Direct oral anticoagulants (DOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban, have less variable pharmacokinetics with rapid onset of action, uniform peak levels, and clearance less affected by extrinsic factors[12]. Given these reasons and ease of administration, DOACs are a desirable alternative to LMWH for patients with active malignancy who may need prolonged anticoagulation. We present a meta-analysis to evaluate the clinical usefulness of all DOACs for the treatment of CAT, considering the efficacy and safety of this category of anticoagulants

Methods

Results

Conclusion