Abstract

Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor under regulatory review for prevention of venous thromboembolism (VTE) after total hip and knee replacement surgery. The efficacy and safety of rivaroxaban for VTE prevention following total hip replacement (THR) was assessed in two, large, randomized, controlled trials. RECORD1 compared rivaroxaban (10 mg once daily) with subcutaneous (sc) enoxaparin (40 mg once daily) over 35 days. The primary outcome (deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality) occurred in 1.1% of rivaroxaban patients and in 3.7% of enoxaparin patients (RRR 70%; p<0.001). Symptomatic VTE occurred in 0.3% and 0.5%, respectively. RECORD2 compared 35 days’ rivaroxaban (10 mg once daily) with 10–14 days’ enoxaparin (40 mg once daily) followed by placebo. The primary outcome occurred in 2.0% of the rivaroxaban group and 9.3% of the enoxaparin + placebo group (RRR 79%; p<0.001). Symptomatic VTE occurred in 0.2% and 1.2%, respectively. There were no statistical differences in major bleeding between the rivaroxaban and enoxaparin regimens in either trial. This analysis assessed the cost-effectiveness of 35 days oral rivaroxaban versus each regimen of subcutaneous enoxaparin for prevention of VTE following THR in Canada.

Methods: An economic model was developed to assess the cost-effectiveness of rivaroxaban versus both durations of enoxaparin after THR in Canada. The analyses were conducted from the perspective of the Ontario (Canadian) Ministry of Health. The incidence of clinical events and their consequences on resource use and quality of life (QoL) were modeled for rivaroxaban and enoxaparin over five years. The incidence of VTE during the period of prophylaxis was based upon RECORD1 and RECORD2, and the incidence of VTE up to 90 days following surgery was extrapolated based on epidemiological data (Quinlan et al., 2007). The incidence of recurrent VTE and post-thrombotic syndrome (PTS) beyond this period was based on clinical data (Prandoni et al., 1997). To calculate resource use we assumed that 19% of patients receiving enoxaparin prophylaxis and those eventually treated for VTE on an outpatient basis would require daily home nursing visits to administer the injections (Harrison et al., 1998). This is likely to be an underestimate in light of other studies and clinical experience of VTE practice in Canada. The costs associated with clinical events (major bleed, VTE and PTS) and home visits was derived from published Canadian sources and expressed in Canadian dollars (C$). Rivaroxaban and enoxaparin costs were included. Utility values, used to demonstrate the impact of clinical events on QoL, were also derived from published literature (Haentjens et al., 2004; Rasanen et al., 2007).

Results: When rivaroxaban and enoxaparin were both administered for 35 days, rivaroxaban was associated with improved clinical outcomes and an average cost saving of C$282.58 per patient. Savings were driven mainly by reduced outpatient administration. Sensitivity analyses showed that rivaroxaban remained more effective and less expensive than enoxaparin in more than 98% of the simulations. When 35 days’ rivaroxaban were compared with 10–14 days enoxaparin, rivaroxaban cost an extra C$90.34 per patient. However, when the improved efficacy with rivaroxaban compared with the 10–14 day enoxaparin regimen was adjusted for QoL, rivaroxaban produced a gain in quality adjusted life years (QALYs) of 0.0027. This translates to an incremental cost per QALY of C$33,323, which is below the commonly-referenced threshold of C$50,000/QALY. Another frequently used VTE prophylaxis in Canada is Fragmin. As Fragmin has a similar efficacy and safety profile to enoxaparin, and has a higher price than enoxaparin in Canada, rivaroxaban is even more cost-effective versus Fragmin.

Conclusions: Rivaroxaban is cost-effective versus 10–14 days’ and 35 days’ enoxaparin for the prevention of VTE following THR in Canada. This is driven by improved efficacy, with respect to clinical event costs and QoL, and the reduction in home nurse visits with use of oral rivaroxaban.

Disclosures: Wells:Bayer Healthcare: Consultancy, Honoraria. Diamantopoulos:Bayer Healthcare: Consultancy. Forster:Bayer Healthcare: Consultancy. Lees:Bayer HealthCare: Employment. McDonald:Bayer HealthCare: Employment.

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