Study participants are listed at the end of the paper.
A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial
Article first published online: 22 DEC 2004
Journal of Thrombosis and Haemostasis
Volume 3, Issue 1, pages 103–111, January 2005
How to Cite
ERIKSSON, B. I., DAHL, O. E., BÜLLER, H. R., HETTIARACHCHI, R., ROSENCHER, N., BRAVO, M.-L., AHNFELT, L., PIOVELLA, F., STANGIER, J., KÄLEBO, P., REILLY, P. and FOR THE BISTRO II STUDY GROUP (2005), A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. Journal of Thrombosis and Haemostasis, 3: 103–111. doi: 10.1111/j.1538-7836.2004.01100.x
Presented as an oral communication at the 18th International Congress on Thrombosis, Ljubljana, Slovenia 20–24 June 2004.
- Issue published online: 22 DEC 2004
- Article first published online: 22 DEC 2004
- Received 6 July 2004, accepted 21 September 2004
- dabigatran etexilate;
- deep vein thrombosis;
- direct thrombin inhibitor;
- total hip replacement;
- total knee replacement;
- venous thromboembolism
Summary. Background: Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolism (VTE) following orthopedic surgery. Methods: In a multicenter, parallel-group, double-blind study, 1973 patients undergoing total hip or knee replacement were randomized to 6–10 days of oral dabigatran etexilate (50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily), starting 1–4 h after surgery, or subcutaneous enoxaparin (40 mg once daily) starting 12 h prior to surgery. The primary efficacy outcome was the incidence of VTE (detected by bilateral venography or symptomatic events) during treatment. Results: Of the 1949 treated patients, 1464 (75%) patients were evaluable for the efficacy analysis. VTE occurred in 28.5%, 17.4%, 16.6%, 13.1% and 24% of patients assigned to dabigatran etexilate 50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily and enoxaparin, respectively. A significant dose-dependent decrease in VTE occurred with increasing doses of dabigatran etexilate (P < 0.0001). Compared with enoxaparin, VTE was significantly lower in patients receiving 150 mg twice daily [odds ratio (OR) 0.65, P = 0.04], 300 mg once daily (OR 0.61, P = 0.02) and 225 mg twice daily (OR 0.47, P = 0.0007). Compared with enoxaparin, major bleeding was significantly lower with 50 mg twice daily (0.3% vs. 2.0%, P = 0.047) but elevated with higher doses, nearly reaching statistical significance with the 300 mg once-daily dose (4.7%, P = 0.051). Conclusions: Oral administration of dabigatran etexilate, commenced early in the postoperative period, was effective and safe across a range of doses. Further optimization of the efficacy/safety balance will be addressed in future studies.