Introduction: Rivaroxaban is a novel, oral, direct Factor Xa inhibitor for the prevention of venous thromboembolism (VTE) after total hip and knee arthroplasty (THA, TKA). The pivotal RECORD trials showed that 35 days’ rivaroxaban significantly reduced total VTE following THA versus both 35-day and 14-day enoxaparin regimens. Following TKA, 14 days’ rivaroxaban significantly reduced total and symptomatic VTE versus 14 days enoxaparin. Major bleeding was similar for rivaroxaban and enoxaparin. An economic model was developed based on these results to assess the cost-effectiveness of rivaroxaban relative to enoxaparin in Sweden.

Methods: The incidence of clinical events and resulting consequences on resource use and quality of life were modelled for rivaroxaban and enoxaparin over 5 years. VTE incidence during the prophylaxis period was based upon RECORD2 (THA) and RECORD3 (TKA) and extrapolated out to 90 days following surgery based on published epidemiological data. These trials were used because they best reflect the treatment length currently applied in clinical practice in Sweden. Recurrent VTE and post-thrombotic syndrome (PTS) beyond 90 days were modelled from published clinical data. Literature indicates that 10% of enoxaparin patients require visits from a district nurse following hospital discharge to administer subcutaneous (sc) enoxaparin, a cost not incurred with oral rivaroxaban. The cost associated with clinical events (major bleed, VTE and PTS) and home care visit was derived from published Swedish sources and expressed in Swedish kroner (SEK). Rivaroxaban and enoxaparin costs were included.

Results: In THA, 35 days’ rivaroxaban produced an additional cost (SEK 119 [€12.59] per patient) versus 14 days enoxaparin. However, rivaroxaban resulted in a gain of quality-adjusted life years (QALYs) and in fewer symptomatic events per patient relative to enoxaparin. This means an extra cost with rivaroxaban of SEK 29,378 (€3,109) per QALY gained and SEK 3,929 (€416) per symptomatic event avoided. Because the cost for treating a VTE range from SEK 12,000 to 30,000, it is less costly to avoid such an event by using rivaroxaban than treating it once it occurs. In TKA, 14 days’ rivaroxaban produced savings of SEK 873 (€92) per patient versus 14 days’ enoxaparin, as well as an improvement in QALYs and a reduction in symptomatic VTE events. Consequently, rivaroxaban was both more effective and less costly. Extensive sensitivity analyses showed that these results persist in a clear majority of situations.

Conclusion: The economic analysis showed that by reducing VTE, and providing an oral alternative to sc enoxaparin, oral rivaroxaban has the potential to significantly improve health outcomes in Sweden at a slightly higher (in THA) or lower (in TKA) cost than existing VTE prophylaxis.

Rivaroxaban is a novel, oral, once-daily, direct Factor Xa inhibitor in advanced development for the prevention and treatment of venous thromboembolism (VTE). This study analysed the potential economic benefit attributable to the use of oral rivaroxaban relative to subcutaneous enoxaparin for extended VTE prophylaxis (35±4 days) after total hip replacement (THR). In RECORD1, rivaroxaban reduced the incidence of the composite primary efficacy endpoint (total VTE, including all-cause mortality) by 70%, compared with enoxaparin (p< 0.001). Symptomatic VTE occurred in 0.3% and 0.5% (p=0.22) of patients receiving rivaroxaban and enoxaparin, respectively. Major bleeding was low and similar in both groups: 0.3% and 0.1% (p=0.18), respectively.

Potential savings associated with oral rivaroxaban were based on any reduction in the incidence of symptomatic VTE events, and reduced administration and monitoring costs. Analyses for both the US and the UK included only non-drug costs incurred by the healthcare sector. It was assumed that nurses spent 3 minutes/day administering enoxaparin and training patients to self-inject; assumed duration of hospital stay was 5 days. UK costs (based on the 2007 NICE Guidelines) also included full blood counts (FBCs) every 3 days, for up to 14 days, in patients receiving enoxaparin.

Two analyses were performed: one assumed no difference in the occurrence of symptomatic VTE between treatments; the other assumed that the observed difference was real, but did not reach statistical significance.

In the first analysis, assuming no difference in symptomatic VTE incidence, the total resource cost in the US was $46/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $3.5/patient. For the UK, the total resource cost was £33/patient for enoxaparin and £7.5/per patient for rivaroxaban: a saving of £25.5/ patient. Savings were driven by reduced monitoring (FBCs) and administration costs.

In the second analysis, assuming the observed difference in symptomatic VTE incidence was real, the US total resource cost was $57/patient for enoxaparin and $42.5/patient for rivaroxaban: a saving of $14.5/patient. For the UK, the total resource cost was £30/patients for enoxaparin and £7.5/patient for rivaroxaban: a saving of £22.5/patient. Savings were again driven by reduced monitoring and administration costs, and also reduced VTE incidence.

Over 400,000 US patients undergo THR, and ~60,000 patients in England and Wales undergo THR annually. Thus, the potential cumulative cost savings with rivaroxaban are considerable.

Venous thromboembolism (VTE) is a potentially fatal complication after total hip replacement (THR) and may be associated with a considerable economic burden. In many centres, thromboprophylaxis using a subcutaneous (sc) anticoagulant in patients undergoing THR is restricted to 14 days or less. Rivaroxaban is a once-daily, oral, direct Factor Xa inhibitor in advanced clinical development for thromboprophylaxis after major orthopaedic surgery; it does not require monitoring or dose adjustment. In a phase III study, RECORD2, oral rivaroxaban 10 mg, given once daily for 35±4 days, significantly reduced the incidence of the primary endpoint (deep vein thrombosis, pulmonary embolism and all-cause mortality), compared with 40 mg sc enoxaparin, given for 14 days (2.0% vs 9.3%, respectively; relative risk reduction 79%; p< 0.001). The incidence of bleeding was low and similar in both groups, despite extended thromboprophylaxis with rivaroxaban. This analysis demonstrates the economic impact of extended thromboprophylaxis with oral rivaroxaban. The effect of rivaroxaban on healthcare costs was based on the primary efficacy results, and the associated reduced administration and monitoring costs, and includes non-drug costs only. The cost of symptomatic VTE was taken from published sources in the US and the UK 2007 NICE Guidelines. It was assumed that nurses spent 3 mins/day administering enoxaparin and training patients to self-inject for outpatient use. Hospital duration was 5 days. In the UK, full blood counts should be taken every 3 days when receiving enoxaparin. The total US health-care resource cost was $192/patient for enoxaparin and $39 for rivaroxaban (excluding drug costs). This saving of $153 was driven by reduced hospital costs associated with fewer VTEs when using rivaroxaban. In the UK, the total healthcare cost/patient was £44 with enoxaparin and £2 with rivaroxaban – savings driven equally by reduced hospitalization and monitoring costs with rivaroxaban prophylaxis. The different cost savings in the US and UK are due to higher US hospital costs. The costs of post-thrombotic syndrome (PTS) were excluded in this analysis. PTS has an estimated 5-year rate of 21% after asymptomatic VTE and 30% after symptomatic VTE, at a total cost/patient of more than $11,000 in the US and £4000 in the UK. Given the reduction in all VTE events with rivaroxaban, there are potential further healthcare cost savings due to reduced PTS. The RECORD2 study showed that extended prophylaxis (35 days) with rivaroxaban was significantly more effective than short-term enoxaparin (14 days) for the prevention of VTE, and was not associated with an increased risk of bleeding. This analysis illustrates an additional benefit of once-daily, oral rivaroxaban in the reduction in healthcare costs related to administration and monitoring.