RIVAROXABAN FOR THROMBOPROPHYLAXIS AFTER TOTAL KNEE REPLACEMENT: THE RECORD3 TRIAL

Abstract

Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. In this phase III trial, the efficacy and safety of thromboprophylaxis with rivaroxaban was compared with enoxaparin in patients undergoing total knee replacement (TKR).

Methods: In RECORD3 – a randomized, double-blind trial – patients received rivaroxaban 10 mg 6–8 hours after surgery and once daily (od) thereafter, or enoxaparin 40 mg od beginning the evening before surgery; both were continued for 10–14 days. The primary efficacy outcome was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and all-cause mortality. Secondary efficacy outcomes included major venous thromboembolism (VTE; the composite of proximal DVT, PE and VTE -related death) and symptomatic VTE. The primary safety outcome was major bleeding, and other safety outcomes included any on-treatment bleeding and haemorrhagic wound complications (the composite of excessive wound haematoma and surgical-site bleeding).

Results: A total of 2531 patients were randomized; 2459 were eligible for inclusion in the safety population and 1702 for the modified intention-to-treat population. The primary efficacy outcome was reported in 9.6% of patients receiving rivaroxaban and 18.9% of patients receiving enoxaparin. This equated to a relative risk reduction of 49% (p< 0.001) with rivaroxaban compared with enoxaparin. The incidence of major VTE was also significantly reduced with rivaroxaban compared with enoxaparin (relative risk reduction 62%, p=0.016). The incidence of symptomatic VTE was significantly lower in the rivaroxaban group than in the enoxaparin group (p=0.005). Major bleeding rates were 0.6% and 0.5% in the rivaroxaban and enoxaparin groups, respectively, and rates of any on-treatment bleeding were 4.9% and 4.8%, respectively. The incidence of haemorrhagic wound complications was 2.1% in the rivaroxaban group and 1.9% in the enoxaparin group.

Conclusions: Rivaroxaban was significantly more effective than enoxaparin for the prevention of VTE after TKR, with a similar safety profile. The oral, direct Factor Xa inhibitor rivaroxaban, given as a fixed, unmonitored dose, may have the potential to change clinical practice for thromboprophylaxis after TKR.