Comparative efficacy and safety of low-intensity warfarin therapy in preventing unprovoked recurrent venous thromboembolism: A systematic review and meta-analysis

Abstract

Background: Although there exists potential risk of bleeding, extended ‘lifelong’ conventional-intensity [international normalized ratio (INR): 2.0-3.0] warfarin anticoagulation is recommended for unprovoked venous thromboembolism (VTE) patients because of risk of recurrent VTE. Whether long-term low-intensity (INR: 1.5-2.0) warfarin therapy reduced the risk of major bleeding without substantially lowered antithrombotic efficacy is not well understood. The aim of this study was to perform a systematic review and meta-analysis to evaluate the risk-benefits of low-intensity warfarin therapy. Methods: We conducted a comprehensive search of electronic databases and included randomized control trials (RCTs) that reported efficacy (recurrent VTE) and safety (bleeding episodes) of low-intensity warfarin therapy compared with conventional-intensity warfarin or placebo from inception through Jun 2016. Results: Four RCTs reporting high GRADE quality evidence were included. Although the relative risk of recurrent VTE with low-intensity therapy was significantly increased [2.96 (95% CI: 1.40 to 6.24), P