Dabigatran Etexilate

Abstract

Dabigatran etexilate (Pradaxa®, Pradax™, Prazaxa®) is indicated for the primary prevention of venous thromboembolic (VTE) events in adults who have undergone elective total hip replacement (THR) or total knee replacement (TKR) surgery. This article reviews the clinical efficacy and tolerability of oral dabigatran etexilate in patients undergoing major orthopaedic surgery, as well as summarizing its pharmacological properties and results of a cost-utility analysis. The discussion of clinical trial data focuses on comparative trials with the EU approved dosage regimen of once-daily subcutaneous enoxaparin sodium 40 mg. Dabigatran etexilate is an oral prodrug of the potent, rapidly acting, reversible, competitive inhibitor of thrombin, dabigatran. Dabigatran has predictable and consistent anticoagulant effects and does not require routine coagulation monitoring or dose titration. In the large, randomized, double-blind, phase III, noninferiority trials, RE-MODEL, RE-NOVATE and RE-NOVATE II, oral dabigatran etexilate, at dosages of 150 and 220 mg once daily, initiated postoperatively was shown to be noninferior to subcutaneous enoxaparin sodium 40 mg once daily (initiated prior to surgery) with regard to the incidence of the composite of total VTE events and all-cause mortality in patients undergoing TKR or THR surgery. In general, oral dabigatran etexilate was well tolerated in clinical trials of patients undergoing major orthopaedic surgery. There were no significant between-group differences in bleeding complications, including major bleeding, clinically relevant non-major bleeding or minor bleeding between the dabigatran etexilate or enoxaparin sodium groups. In addition, a cost-utility analysis from the perspective of the UK National Health Service indicated that dabigatran etexilate 220 mg once daily is dominant (i.e. more effective and less costly) to enoxaparin sodium 40 mg once daily in patients undergoing THR or TKR. Additional head-to-head comparisons would be beneficial to more definitively position dabigatran etexilate relative to other available oral treatment options for VTE prophylaxis, such as rivaroxaban and apixaban. In the meantime, dabigatran etexilate offers a convenient, effective and generally well tolerated treatment option for the prophylaxis of VTE in patients undergoing TKR and THR surgery.