Cost–Effectiveness of Rivaroxaban Versus Heparins for Prevention of Venous Thromboembolism After Total Hip or Knee Surgery in Sweden

Lars Ryttberg; Alex Diamantopoulos; Fiona Forster; Michael Lees; Anina Fraschke; Ingela Björholt


Expert Rev Pharmacoeconomics Outcomes Res. 2011;11(5):601-615. 

In This Article


The design of the economic evaluation incorporated both acute and long-term complications of the condition. A trial-based analysis would not include all relevant costs and QoL impairment from VTE and would, therefore, underestimate the cost–effectiveness of rivaroxaban.

The incidences of VTE and its complications were based on evidence from the Phase III trials of rivaroxaban versus enoxaparin. From the four randomized clinical trials in the Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) program[3,4,8,9] the analysis focused on those two that are most relevant to the Swedish setting;[3,4] those based on the duration of prophylaxis. In Sweden, the recommended duration of prophylaxis is 10–14 days; Lundkvist and colleagues report that only 5% of patients would receive prophylaxis beyond the initial 14-day period.[7] For the THR population, RECORD2[3] was selected, in which enoxaparin prophylaxis of up to 14 days followed by placebo was compared with extended prophylaxis with rivaroxaban for up to 35 days after THR. For the TKR population, RECORD3,[4] in which up to 14 days of enoxaparin was compared with up to 14 days of rivaroxaban in patients who had undergone TKR, was selected.

Because dalteparin (another LMWH) is also commonly administered for prophylaxis of VTE in Sweden, the evaluation included a scenario analysis of 10 mg rivaroxaban versus 5000 units of dalteparin. A literature review was conducted to assess the relative efficacy and safety of enoxaparin versus dalteparin, in order to indirectly compare dalteparin with rivaroxaban.

The review did not identify any randomized controlled trials comparing enoxaparin and dalteparin. A pilot study was performed by the TIFDED Study Group[10] comparing enoxaparin, dalteparin and danaparoid. Two retrospective studies were also found comparing dalteparin with enoxaparin.[11,12] However, neither of the studies that directly compared enoxaparin with dalteparin provided evidence of significant differences between these agents in the incidence of thromboembolic complications or major bleeding following orthopedic surgery. Studies that compared fondaparinux with LMWHs and UFHs also showed no indication of differences between dalteparin and enoxaparin.[12,13] Therefore, the economic analysis assumed a drug class effect for both LMWHs and assumed that dalteparin had a similar efficacy and safety to rivaroxaban as that demonstrated for enoxaparin by Kakkar et al.[3] and Lassen et al..[4]

The economic analysis employed a model as a means of synthesizing all relevant clinical information and cost estimates. The model took the form of a multimodular analysis following the patient cohort after surgery (THR or TKR) and extrapolated observed events to include relevant long-term complications for a period of 5 years. The model structure was divided into three modules: prophylaxis, post-prophylaxis and long-term complications. The first two modules constituted the acute phase and were represented by a decision tree (Figure 1), while the third module represented the chronic phase and was described by a Markov process (Figure 2).

Figure 1.

Structure of economic model: prophylaxis and post-prophylaxis modules.
DVT: Deep vein thrombosis; PE: Pulmonary embolism; RECORD: Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism; VTE: Venous thromboembolism.

Figure 2.

Structure of long-term complications module.
CTPH: Chronic thromboembolic pulmonary hypertension; DVT: Deep vein thrombosis; PE: Pulmonary embolism; PTS: Post-thrombotic syndrome; VTE: Venous thromboembolism.


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