Cost/effectiveness model of dabigatran in the prevention of venous thromboembolism in major orthopedic surgery: Adaptation for Italy

Venous thromboembolic events (VTE) represent a dangerous complication of major orthopedic surgery, especially in total hip replacement (THR) and total knee replacement (TKR) procedures. Dabigatran etexilate (DBG), a direct and reversible thrombin inhibitor, has proven its non-inferiority with respect to enoxaparin 40mg once-daily, a low molecular weight heparin (LMWH), in the prevention of VTE in patients undergoing THR and TKR, in the RE-NOVATE and RE-MODEL trials, respectively. The objective of this analysis was to estimate cost/effectiveness and cost/utility of DBG compared to standard care for the prevention of VTE in Italy. A decision analytic, Markov-chain based model, originally developed for the UK, was adapted to the Italian context. The adaptation involved cost and demographic characteristics, clinical and utility data were not altered. Costs were taken from national observational studies, where available. Otherwise, current prices and tariffs were applied. Resource consumption was derived from practice guidelines or taken from the UK model. According to the prevalent national practice, extended prophylaxis is considered for both surgical procedures. The time horizon of the analysis was patients’ lifetimes. In order to consider different alternatives for drug dispensation and, consequently, National Health Service acquisition costs, alternative scenarios were developed. A further scenario, excluding LMWHs administration costs (“worst-case” scenario), was considered. Compared to LMWHs, DBG was associated with an expected increase of 0.019 life-years (LYs) and 0.014 quality-adjusted life-years (QALYs) per THR patient and of 0.024 LYs and 0.019 QALYs per TKR patient. DBG-related costs were lower than LMWH in both procedures, with a mean difference ranging from 89 to 116 € for THR, and 107 to 142 for TKR, depending on the LMWH product. Higher acquisition costs for DBG were completely offset and inverted by avoided administration expenses and, to a lesser extent, by savings in VTE management. The results of alternative scenarios confirm the dominance of DBG, with a net saving ranging between 119 €, when both drugs were obtained by auction, and 32 €, when the auction price was applied but DBG was dispensed through territorial pharmacies. The corresponding estimates for TKR were 148 and 54 €. In the “worst-case” scenario, DBG was no longer dominant, with a cost per LYs of 2,788 and 4,514 € and a cost per QALY gained of 3,619 and 5,926 €, for TKR and THR respectively. In conclusion, DBG dominated LMWHs, and was cost-saving and non-inferior in terms of efficacy and safety, except for in the “worst-case” scenario, in which the incremental cost/effectiveness ratio estimate was lower than commonly accepted thresholds in health economics.