Effectiveness and Tolerability of Anticoagulants for Thromboprophylaxis after Major Joint Surgery: a Network Meta-Analysis

Abstract

Background/aims: Venous thromboembolism (VTE) is the most common complication after major joint surgery. VTE can easily develop into pulmonary embolism (PE), leading to cardiopulmonary dysfunction or sudden death. We aimed to comprehensively analyse the thromboprophylactic drugs that are used to prevent thrombosis and reduce bleeding risk.

Methods: We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that evaluated the use of thromboprophylaxis after major joint surgery. The major outcomes were the numbers of all-cause VTE and bleeding events, and the secondary outcomes were major VTE and major bleeding/clinically relevant non-major bleeding events. A random-effects network meta-analysis was used to assess the effectiveness and tolerability of each anticoagulant after major joint surgery.

Results: We included 104 trials that assessed 110,643 patients in our meta-analysis. The cluster ranking of major outcomes indicated that FXI-ASO, ardeparin, aspirin, and apixaban were ideal for preventing all-cause VTE and avoiding all bleeding events. Nadroparin, recombinant hirudin, and rivaroxaban effectively inhibited VTE but were associated with a high risk of bleeding. For secondary outcomes, we found that betrixaban, dalteparin, warfarin, and eribaxaban were ideal for preventing major VTE and reducing major bleeding, while rivaroxaban effectively inhibited major VTE but was associated with a high risk of major/clinically relevant non-major bleeding. A sensitivity analysis showed that the effect of apixaban was more robust for major outcomes, while aspirin was more robust for preventing all-cause bleeding events. In secondary outcomes, the effect of warfarin was more robust, while apixaban was still considered an ideal treatment to inhibit major VTE and bleeding events.

Conclusion: Our study indicates that FXI-ASO, ardeparin, aspirin, and apixaban are ideal for preventing all-cause VTE and reducing all bleeding events, among which apixaban is the most reliable. Betrixaban, dalteparin, warfarin, and eribaxaban are ideal for preventing major VTE and reducing major/clinically relevant non-major bleeding events, among which warfarin is the most reliable.

Keywords: Anticoagulants; Arthroplasty; Meta-analysis; Replacement; Thromboprophylaxis.