Dabigatran Etexilate for Total Hip and Knee Replacement

Atlanta—Patients undergoing total hip or knee replacement who took 220 mg of dabigatran etexilate daily had few major bleeding events regardless of their body mass index (BMI), renal function, or age, according to an international, open-label, prospective, observational, single-arm study.

Results were presented during a poster session at the ASH meeting. The poster was titled Real World Study of Dabigatran Etexilate for Thromboprophylaxis in Over 5000 Hip or Knee Replacement Patients: Favorable Safety Profile in Subgroups with Different BMI, Renal Function, and Age.

The authors noted patients who have total hip or knee replacement have an increased risk of venous thromboembolic events (VTE). The FDA approved dabigatran etexilate, an oral anticoagulant, in October 2010 to prevent stroke and blood clots in patients with atrial fibrillation.

Phase 3 trials have shown 220 mg of dabigatran etexilate is as effective as 40 mg of enoxaparin in preventing VTE in patients undergoing orthopedic surgery. The drug also has a favorable safety profile.

In this study, the authors recruited 5292 patients at 110 sites in 9 European countries. Patients were included if they were ≥18 years of age, were undergoing total hip or total knee replacement surgery, and were eligible for dabigatran etexilate, including an initial 110-mg dose 1 to 4 hours after surgery.

Median age was 64 years, and 42.2% of patients were males. Median BMI was 28.4 kg/m² and the median creatinine clearance was 95.4 mL/minute, with 70.4% of patients having creatinine clearance ≥80 mL/minute and 26.0% having creatinine clearance from 50 to 80 mL/minute.

The incidence of major bleeding events was 0.72% (95% confidence interval [CI], 0.51%-0.98%), and the rate was not affected when comparing age <65 years (0.63%) and ≥65 years (0.81%), according to the authors. They also noted the incidence of major bleeding events was similar in BMI ≤35 kg/m²: 0.71% for BMI <25 kg/m², 0.69% for BMI 25 to <30 kg/m², and 0.39% for BMI 30 to 35 kg/m². However, the incidence of major bleeding events was 1.47% in patients with BMI >35 kg/m², which the authors said may have occurred because of more difficult surgery sites and treatment in those patients.

The incidence of major bleeding events was 0% in patients with creatinine clearance from 30 to <50 mL/minute, 0.73% in patients with creatinine clearance from 50 to <80 mL/minute, and 0.75% in patients with creatinine clearance >80 mL/minute.

The incidence of symptomatic VTE and all-cause mortality was 1.04% for all patients and was similar in patients when stratifying by age, BMI, and creatinine clearance. The authors noted the type of surgery did not impact the incidence of major bleeding events: it was 0.69% for patients undergoing total hip replacement (95% CI, 0.42%-1.08%) and 0.74% for patients undergoing total knee replacement (95% CI, 0.45%-1.16%). The composite of symptomatic VTE and death was 1.56% in the total knee replacement group (95% CI, 1.12%-2.12%) and 0.55% in the total hip replacement group (95% CI, 0.31%-0.90%).

Further, the authors found the overall incidence of treatment-emergent adverse events was 18.7%; 4.9% of patients discontinued taking dabigatran etexilate due to an adverse event and 5.5% of patients had drug-related adverse events.

This study was funded by Boehringer Ingelheim.