Oral Dabigatran Etexilate Versus Enoxaparin for Prevention of Venous Thromboembolism After Total Hip or Knee Arthroplasty: A Pooled Analysis of Four Randomized Trials

Abstract 2312 Introduction: Thromboprophylaxis after major orthopaedic surgery reduces the risk of venous thromboembolism (VTE). Four randomized, double-blind, non-inferiority trials compared oral dabigatran etexilate doses of 220 mg or 150 mg once daily (qd) with subcutaneous enoxaparin for the primary prevention of VTE in patients undergoing elective total hip or knee arthroplasty. In the hip arthroplasty trials (RE-NOVATE® and RE-NOVATE® II) the treatment duration was 28–35 days; in the knee arthroplasty trials it was 6–10 days (RE-MODEL™) and 12–15 days (RE-MOBILIZE®). Three of the trials used a comparator enoxaparin regimen of 40 mg qd started the evening before surgery, while in RE-MOBILIZE® enoxaparin was given in the North American regimen of 30 mg twice daily starting 12–24 hours after surgery. In countries where dabigatran etexilate is approved, a dose of 220 mg qd is recommended for most patients; 150 mg qd is for patients with moderate renal impairment (creatinine clearance 30–50 mL/min) and elderly patients (> 75 years). Methods: The primary efficacy outcome for each trial was a composite of total VTE (venographic and symptomatic) and death from all causes during the treatment period. The main composite outcome for the pooled analysis of the four trials was major VTE (proximal deep vein thrombosis or non-fatal pulmonary embolism) plus VTE-related death, which was the main secondary endpoint on the individual trial level. This endpoint was chosen for the pooled analysis, because the event rates are similar across hip and knee arthroplasty, whereas the rate of total VTE and all-cause mortality is substantially higher across all treatment groups for the knee compared to the hip. The main safety outcome was major bleeding (clinically overt bleeding associated with ≥ 20 g/L fall in haemoglobin or transfusion ≥ 2 units of packed cells or blood; or bleeding that was fatal, retroperitoneal, intracranial, intraocular, intraspinal, warranted treatment cessation or led to reoperation) measured from a preoperative baseline in all four trials. Results: In the pooled analysis of the four trials, the main efficacy outcome of major VTE and VTE-related death occurred in 2.8% (80/2838) of the dabigatran etexilate 220 mg group, 3.8% (78/2071) of the dabigatran etexilate 150 mg group and 3.5% (102/2891) of the enoxaparin group; risk difference (RD) versus enoxaparin –0.7% (95% confidence interval [CI] –1.6% to 0.2%) for 220 mg and 0.2% (95% CI –0.8% to 1.3%) for 150 mg. The composite of total VTE and all-cause mortality occurred in the pooled hip trials in 6.8% (114/1672) of the dabigatran etexilate 220 mg group, 8.6% (75/874) of the dabigatran etexilate 150 mg group and 7.7% (129/1683) of the enoxaparin group; RD versus enoxaparin –0.8% (95% CI –2.6% to 0.9%) for 220 mg and 0.9% (95% CI –1.3% to 3.2%) for 150 mg. Major bleeding occurred in 1.4% (52/3692), 1.1% (29/2737) and 1.3% (48/3719), of the dabigatran etexilate 220 mg, 150 mg and enoxaparin groups, respectively; RD versus enoxaparin 0.1% (95% CI –0.4% to 0.6%) for 220 mg and –0.2% (95% CI –0.8 to 0.3%) for 150 mg. Conclusions: Prophylaxis with oral dabigatran etexilate 220 mg qd or 150 mg qd was as effective as subcutaneous enoxaparin at reducing the risk of total VTE and all-cause mortality after total hip arthroplasty with a similar bleeding profile. With regard to the endpoint of major VTE and VTE-related death, dabigatran etexilate 220 mg and 150 mg showed similar efficacy versus enoxaparin in the pooled hip and knee arthroplasty trials. Disclosures: Huo: Boehringer Ingelheim: Consultancy. Kurth:Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Clemens:Boehringer Ingelheim: Employment. Hantel:Boehringer Ingelheim: Employment. Feuring:Boehringer Ingelheim: Employment. Friedman:Johnson and Johnson: Consultancy. Eriksson:Bristol-Myers Squibb: Consultancy; Bayer: Consultancy; Astellas: Consultancy.