Administration Advantages and Cost-Savings with Dabigatran Etexilate Versus Parenteral Agents for Thromboprophylaxis After Major Orthopaedic Surgery in the Netherlands.

New oral thromboprophylactic agents for prophylaxis of venous thromboemobolism (VTE) in patients who have undergone total hip replacement (THR) or total knee replacement (TKR) surgery, have potential administration advantages over parenteral prophylaxis with low molecular weight heparins (LMWHs) or fondaparinux. Dabigatran etexilate (Pradaxa^®) is a novel oral direct thrombin inhibitor for VTE prophylaxis after major orthopaedic surgery. Advantages of such oral agents over parenteral prophylaxis might include but are not limited to reduced resource use for (i) teaching patients to self-inject; (ii) home-care visits for parenteral administration by nurses due to self-administration problems; and (iii) absence of heparin induced thrombocytopenia (HIT). This analysis was designed to investigate the prevalence of administration problems with parenteral thromboprophylaxis. Furthermore, based on proven non-inferiority and data on the prevalence of administration problems, the aim of this study was to conduct a cost-minimization analysis of oral dabigatran etexilate versus parenteral LMWHs and fondaparinux from the Dutch National Health Service perspective.

A retrospective telephone interview was conducted among patients who have undergone THR or TKR surgery. Patients were included from three Dutch hospitals in 2008. Several questions were asked to measure health-care resource use and potential problems related to self-administration of parenteral agents in the home-setting. Dutch drug-utilization patterns and health-care resource data were combined with local unit costs to calculate the cost of thromboprophylaxis with dabigatran etexilate, LMWH and fondaparinux formulations. Probabilistic sensitivity analysis was performed to account for uncertainty around all relevant parameters included. All costs were expressed in 2008 values, without discounting as all costs are incurred in a maximum period of 10 weeks within the same financial year.

687 patients (response rate of 87.4%) were interviewed. A total of 511 (74.4%) of these patients used parenteral thromboprophylaxis at home. 48.8% of the interviewed patients reported administration problems varying from pain, bruises and itches and almost 60% of all THR/TKR patients would prefer oral over parenteral thromboprophylaxis. Home-care visits for parenteral administration problems were required by 9.9% (95%CI: 6.4;13.4) and 9.6% (95%CI: 5.8;13.4) of THR and TKR patients, respectively. Based on costs for 1000 patients treated with dabigatran etexilate versus current distribution of LMWH usage in the Netherlands, per patient cost-savings with dabigatran etexilate were estimated at €24.63 (95%CI: -0.56;54.19) and €18.39 (95%CI: -2.54;41.52) for THR and TKR, respectively. The probability that dabigatran etexilate would be cost-saving is 97.1% and 95.6% for THR and TKR, respectively. These cost-savings were even higher when including fondaparinux with per patient cost-savings of €84.87 (95%CI: 58.04;117.64) and €33.41 (95%CI: 12.27;57.36) for THR and TKR, respectively. See table for summarized results. Separate calculations for dabigatran etexilate versus nadroparin and dalteparin in THR resulted in a probability of achieving cost-savings with dabigatran etexilate of 19.0% and 100%, respectively. For TKR these probabilities for dabigatran etexilate versus nadroparin and dalteparin were estimated at 37.0% and 100%.

This retrospective study indicated that a majority of THR/TKR patients experience problems with self-administration of parenteral thromboprophylaxis in the home-setting. Based on averted home-care for problems with parenteral self-administration, thromboprophylaxis with dabigatran etexilate is cost-saving in patients undergoing THR/TKR from the perspective of the Dutch National Health Service.

Boersma: Boehringer Ingelheim bv: Consultancy, Research Funding. Kappelhoff: Boehringer Ingelheim bv: Employment. Postma: Boehringer Ingelheim bv: Consultancy, Research Funding.