Dabigatran Etexilate: Pivotal Trials for Venous Thromboembolism Prophylaxis After Hip or Knee Arthroplasty

Abstract

Dabigatran etexilate, an oral direct thrombin inhibitor, was investigated in 3 large phase III trials for the prevention of venous thromboembolism (VTE) after total hip arthroplasty (RE-NOVATE, N = 3494) or total knee arthroplasty (RE-MODEL, N = 2076 and RE-MOBILIZE, N = 2615). RE-NOVATE and RE-MODEL were conducted mainly in Europe, and RE-MOBILIZE was conducted predominantly in the United States and Canada. This review discusses the results of these trials. In all 3 trials, 2 doses, 220 mg and 150 mg once daily, were compared with enoxaparin. Both RE-MODEL and RE-NOVATE demonstrated noninferiority for the primary outcome (a composite of total VTE events and all-cause mortality), P = .0003 and P < .0001, respectively, for these trials. In 2008, these data formed the basis for European and Canadian approval. While RE-MOBILIZE did not demonstrate noninferiority for the primary outcome (25.3% for enoxaparin vs 31.1% for 220 mg, risk difference +5.8%, 95% CI, 0.8-10.8; P = .02 and 33.7% for 150 mg, risk difference +8.4%, 95% CI, 3.4-13.3; P = .0009), both treatments were similar for the secondary composite outcome (major VTE plus VTErelated mortality; 3.4% with 220 mg, 3.0% with 150 mg, and 2.2% with enoxaparin) and symptomatic deep vein thrombosis (0.8%, 0.7%, and 0.6%). There were no differences in the bleeding rates, hepatic enzyme elevations, or acute coronary syndrome events between the 2 treatments. With the practical advantages of once-daily oral dosing, dabigatran etexilate can be considered an attractive alternative to conventional thromboprophylaxis regimens in patients undergoing elective total hip and knee arthroplasty.