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

被引:331
作者
Eriksson, BI [1 ]
Dahl, OE
Büller, HR
Hettiarachchi, R
Rosencher, N
Bravo, ML
Ahnfelt, L
Piovella, F
Stangier, J
Kälebo, P
Reilly, P
机构
[1] Sahlgrens Univ Hosp, Dept Orthopaed, SE-41685 Gothenburg, Sweden
[2] Buskerud Cent Hosp, Drammen, Norway
[3] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands
[4] Boehringer Ingelheim bv, Alkmaar, Netherlands
[5] Cochin Univ Hosp, Paris, France
[6] Boehringer Ingelheim France, Reims, France
[7] Falkoping Hosp, Falkoping, Sweden
[8] Policlin San Matteo, IRCCS, I-27100 Pavia, Italy
[9] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany
[10] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA
关键词
dabigatran etexilate; deep vein thrombosis; direct thrombin inhibitor; total hip replacement; total knee replacement; venous thromboembolism;
D O I
10.1111/j.1538-7836.2004.01100.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:103 / 111
页数:9
相关论文
共 16 条
[1]   The pharmacology and management of the vitamin K antagonists [J].
Ansell, J ;
Hirsh, J ;
Poller, L ;
Bussey, H ;
Jacobson, A ;
Hylek, E .
CHEST, 2004, 126 (03) :204S-233S
[2]   VENTILATION-PERFUSION STUDIES IN SUSPECTED PULMONARY-EMBOLISM [J].
BIELLO, DR ;
MATTAR, AG ;
MCKNIGHT, RC ;
SIEGEL, BA .
AMERICAN JOURNAL OF ROENTGENOLOGY, 1979, 133 (06) :1033-1037
[3]   Ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement:: the METHRO II randomised trial [J].
Eriksson, B ;
Bergqvist, D ;
Kälebo, P ;
Dahl, OE ;
Lindbratt, S ;
Bylock, A ;
Frison, L ;
Eriksson, UG ;
Welin, L ;
Gustafsson, D .
LANCET, 2002, 360 (9344) :1441-1447
[4]   Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement:: BISTRO I [J].
Eriksson, BI ;
Dahl, OE ;
Ahnfelt, L ;
Kälebo, P ;
Stangier, J ;
Nehmiz, G ;
Hermansson, K ;
Kohlbrenner, V .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2004, 2 (09) :1573-1580
[5]   The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement:: the EXPRESS study [J].
Eriksson, BI ;
Agnelli, G ;
Cohen, AT ;
Dahl, OE ;
Lassen, MR ;
Mouret, P ;
Rosencher, N ;
Kälebo, P ;
Panfilov, S ;
Eskilson, C ;
Andersson, M .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2003, 1 (12) :2490-2496
[6]   Prophylaxis of venous thromboembolism with subcutaneous melagatran in total hip or total knee replacement:: Results from Phase II studies [J].
Eriksson, BI ;
Ögren, M ;
Eriksson, UG ;
Kälebo, P ;
Ahnfelt, L ;
Björkström, S ;
Sjöstedt, Å ;
Folestad, A ;
Arfwidsson, AC ;
Elvander, CS ;
Frison, L .
THROMBOSIS RESEARCH, 2002, 105 (05) :371-378
[7]   Prevention of venous thromboembolism [J].
Geerts, WH ;
Pineo, GF ;
Heit, JA ;
Bergqvist, D ;
Lassen, MR ;
Colwell, CW ;
Ray, JG .
CHEST, 2004, 126 (03) :338S-400S
[8]   The pharmacodynamics and pharmacokinetics of the oral direct thrombin inhibitor ximelagatran and its active metabolite melagatran: A mini-review [J].
Gustafsson, D ;
Elg, M .
THROMBOSIS RESEARCH, 2003, 109 :S9-S15
[9]   Optimization of ascending phlebography of the leg for screening of deep vein thrombosis in thromboprophylactic trials [J].
Kalebo, P ;
Anthmyr, BA ;
Eriksson, BI ;
Zachrisson, BE .
ACTA RADIOLOGICA, 1997, 38 (02) :320-326
[10]  
Kalebo P, 1996, THROMB HAEMOSTASIS, V76, P893