Dabigatran etexilate appears to be a safe, effective, and more convenient alternative to enoxaparin after hip replacement surgery.
Anticoagulation for 5 to 11 days after hip replacement surgery can reduce the incidence of venographically detected deep venous thrombosis (DVT) to about 20%. Longer treatment courses may further reduce the incidence, but adherence to anticoagulation often declines after hospital discharge. Dabigatran etexilate is an investigational oral direct thrombin inhibitor that has been shown to be safe and effective for the prevention of DVT after orthopedic surgery and does not require therapeutic monitoring.
In a manufacturer-funded, double-blind, noninferiority trial, 3494 patients were randomized to receive dabigatran etexilate (150 or 220 mg daily) or subcutaneous enoxaparin (40 mg daily) for 28 to 35 days after hip replacement surgery (all patients also received matching placebos). Overall, 2651 patients (76%) had adequate venographic studies at the end of treatment and were evaluated for the primary composite endpoint of pulmonary embolism, symptomatic or venographic DVT, or all-cause mortality.
Both doses of dabigatran were statistically noninferior to enoxaparin: The primary endpoint occurred in 8.6% and 6.0% of patients who received low- and high-dose dabigatran, respectively, compared with 6.7% of patients who received enoxaparin. The incidence of major bleeding was similar (2% or lower) in all groups, with half of events occurring before the first dose of oral medication or placebo.
Comment: Dabigatran etexilate appears to be a safe, effective, and more convenient alternative to enoxaparin after hip replacement surgery. This drug is also undergoing testing as an alternative to warfarin for patients with atrial fibrillation or venous thromboembolism. Another oral direct thrombin inhibitor, ximelagatran, nearly reached the U.S. market several years ago, but fell short because of hepatotoxicity (Journal Watch Mar 1 2005). In the current study, dabigatran was not associated with increased incidence of liver enzyme abnormalities.
Published in Journal Watch General Medicine October 9, 2007
Eriksson BI et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: A randomised, double-blind, non-inferiority trial. Lancet 2007 Sep 15; 370:949.