PURPOSE:This meta-analysis evaluated the efficacy of rivaroxaban for the prevention of symptomatic venous thromboembolism in the three completed pivotal RECORD studies, which compared rivaroxaban with enoxaparin 40 mg once daily (od).
METHODS:Patients (n=9581) were randomized to receive oral rivaroxaban 10 mg od starting at least 6–8 hours after surgery, or subcutaneous enoxaparin (40 mg od starting the evening before surgery). In RECORD1, all patients undergoing total hip replacement (THR) received extended thromboprophylaxis for 35 days. In RECORD2, patients undergoing THR received rivaroxaban for 35 days or enoxaparin for 10–14 days. In RECORD3, patients undergoing total knee replacement received prophylaxis for 10–14 days. All outcomes, including objectively confirmed symptomatic outcomes, were blindly adjudicated by an independent committee. In all three studies, the rivaroxaban regimens significantly reduced the incidence of the primary outcome (the composite of any deep vein thrombosis [DVT], non-fatal pulmonary embolism [PE], and death) and major VTE (proximal DVT, non-fatal PE, and VTE-related death), compared with the enoxaparin regimens, without increasing the risk of bleeding.This meta-analysis evaluated the effect of rivaroxaban on the composite of symptomatic VTE (DVT and PE) and death, and major bleeding at 2 weeks (predefined), and at the end of the planned medication period, in the safety population.
RESULTS:Rivaroxaban significantly reduced the incidence of symptomatic VTE and death compared with enoxaparin (2 weeks: 0.4% vs 0.8%, respectively, odds ratio [OR] 0.44, 95% confidence intervals [CIs] 0.23, 0.79, p=0.005), and the rivaroxaban regimens were more effective at the end of planned study medication (0.5 vs 1.3, respectively, OR 0.38, 95% CIs 0.22, 0.62, p<0.001). Both groups had similar rates of major bleeding (2 weeks: 0.2% vs 0.2%, respectively, p=0.662; end of planned study medication: 0.3% vs 0.2%, respectively, p=0.305).
CONCLUSION:The rivaroxaban regimens significantly reduced symptomatic VTE and death, compared with the enoxaparin regimens, without an increased risk of bleeding in patients undergoing major orthopaedic surgery.
CLINICAL IMPLICATIONS:Rivaroxaban significantly reduces clinically important VTE outcomes, without compromising safety.
DISCLOSURE:Alexander Turpie, Consultant fee, speaker bureau, advisory committee, etc. Consultant fees received from Bayer HealthCare AG and Scios Inc.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Rivaroxaban is an oral anticoagulant in advanced clinical development (phase III) for thromboprophylaxis after major orthopaedic surgery, treatment of venous thromboembolism, and stroke prevention in atrial fibrillation. Three phase III trials were previously reported at ASH 2007. The study reported in the abstract submitted here describes a meta-analysis of these three trials.