Dabigatran in the prevention of venous thromboembolism after major orthopedic surgery

Abstract

Venous thromboembolism (VTE) is a very frequent surgical complication, especially in major orthopedic procedures. Prophylaxis with pharmacological agents, including warfarin and subcutaneous injection of either low-molecular weight heparin (LMWH) or low-dose unfractionated heparin, and/or with mechanical methods has been shown to be effective and safe. Despite recommendations on the routine implementation of these prophylaxis methods, some surveys demonstrate that many patients currently don’t receive any prophylaxis. The recent introduction of dabigatran etexilate, a novel oral direct thrombin inhibitor approved for VTE prophylaxis in total knee and hip substitution, represents a major advance in the provision of efficient anticoagulation therapy. Two pivotal randomized controlled multicenter trials assessed non-inferiority of dabigatran 150/220 mg/day versus enoxaparin 40 mg/day in the prevention of VTE after hip and knee replacement. From an economical point of view, an English modeling study on dabigatran cost/effectiveness showed it to be associated with lower cost and slightly higher gain in Quality Adjusted Life Years, thus dominating enoxaparin. Other analyses obtained results consistent with these, estimating inferior costs related to the use of dabigatran with respect to low weight heparin; this difference was mainly due to health personnel work for heparins subcutaneous administration. In Italy, acquisition costs for a 28-35 days therapeutic cycle of main antithrombotic drugs vary between 70 and 170 €, according to different distribution policy. Dabigatran, with a cost of 117 €, holds a medial position. Cost savings related to oral administration may partially offset the price difference between dabigatran and the less expensive options among LMWHs or, compared with the more expensive ones, add to pharmaceutical cost savings. In order to increase the effectiveness of VTE prophylaxis, the improvement of patient adherence to the prescribed strategy is needed. On this plane, dabigatran may be associated to some advantages, like the lack of drug and food interactions, the need for less frequent coagulation monitoring compared to vitamin K antagonists, and obviation of daily injections of parenteral agents. In conclusion, these considerations suggest that dabigatran may prove an interesting alternative in VTE prevention in orthopedic surgery.