Abstract
Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor submitted to US FDA for approval for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery and is also in development for prevention and treatment of thromboembolic disorders. A recently published Phase III trial, RECORD1, compared rivaroxaban 10 mg once daily (od) with subcutaneous (sc) enoxaparin 40 mg od as VTE prophylaxis over 35 days in patients following total hip replacement (THR). The primary outcome (deep vein thrombosis, 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). The recently published RECORD2 compared 35 days’ rivaroxaban prophylaxis (10 mg od) with a short-term,10–14 day enoxaparin regimen (40 mg od) 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). The two drugs had similar safety profiles. This analysis compares the cost-effectiveness of 5 weeks’ prophylaxis with rivaroxaban in patients undergoing THR from US payer’s perspective.
Methods: Three Economic decision models were developed based on the efficacy and safety parameters from individual RECORD1 and RECORD2 trials as well as combined RECORD1and 2 results, due to different treatment durations with enoxaparin (35 days in RECORD1 and 14 days in RECORD 2) vs. 35 days’ rivaroxaban. The models followed patients for up to 1 year post THA. The clinical efficacy (deep vein thrombosis [DVT], pulmonary embolism [PE], and symptomatic VTE events) and safety profiles of both drugs during the period of prophylaxis were obtained from the published RECORD1 and 2 trials, while 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 beyond this period was based on clinical data (Prandoni et al., 1997). The treatment costs for symptomatic VTE and major bleeding were taken from published sources in the US. For costing purposes, the duration of hospitalization for THA was obtained from a published US orthopaedic registry (3 days). It was also conservatively assumed that no incremental nurse time or home visit costs were associated with sc enoxaparin injection. Since rivaroxaban is not yet approved in the US, the economic model assumed similar drug acquisition costs to enoxaparin 40mg od.
Results: Using rivaroxaban for 35 days appears to be a cost-effective and, in some instances, a cost-saving option compared with enoxaparin. The 1-year economic model based on RECORD2 (vs. 14 days’ enoxaparin) showed that 35 days’ rivaroxaban was associated with an incremental cost per symptomatic event avoided of $5,945. The analysis based on RECORD1 with a 35-day duration with both drugs showed that rivaroxaban resulted in an $82 cost saving, and a reduction of 6 symptomatic events per 1000 patients undergoing THR. Similarly, the –combined analysis based on RECORD 1and 2 showed a $19 cost saving and a reduction of 14 symptomatic events per 1000 patients favoring rivaroxaban. This improvement was driven primarily by the reduced costs of hospitalization for symptomatic events. Sensitivity analyses including the costs associated with home nurse time or training patients to self-administer enoxaparin showed potential for more cost-savings if patients receive oral rivaroxaban.
Conclusions: Despite the clinical benefits of extended prophylaxis for up to 5 weeks with enoxaparin, and its recommendations in the guidelines, its use is limited in current US clinical practice, potentially due to inconvenience and high cost. Oral rivaroxaban given for 5 weeks has the potential to be cost effective, based on its superior efficacy over enoxaparin in patients undergoing THR. With more than 150,000 US patients having hip replacement annually, the benefits of using rivaroxaban could be significant.
Unit-of-Use Versus Traditional Bulk Packaging
