Extended Use of Dabigatran, Warfarin, or Placebo in Venous Thromboembolism

被引:732
作者
Schulman, Sam [1 ,2 ,3 ]
Kearon, Clive [1 ,2 ]
Kakkar, Ajay K. [5 ,6 ]
Schellong, Sebastian [7 ]
Eriksson, Henry [4 ]
Baanstra, David [8 ]
Kvamme, Anne Mathilde [9 ]
Friedman, Jeffrey [10 ]
Mismetti, Patrick [11 ]
Goldhaber, Samuel Z. [12 ,13 ]
机构
[1] McMaster Univ, Dept Med, Hamilton, ON, Canada
[2] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada
[3] Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden
[4] Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden
[5] Thrombosis Res Inst, London, England
[6] UCL, London WC1E 6BT, England
[7] Municipal Hosp Friedrichstadt, Med Div 2, Dresden, Germany
[8] Boehringer Ingelheim GmbH & Co KG, Clin Res, Alkmaar, Netherlands
[9] Boehringer Ingelheim GmbH & Co KG, Clin Res, Asker, Norway
[10] Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA
[11] Bellevue Hosp, Dept Vasc Pathol, St Etienne, France
[12] Brigham & Womens Hosp, Boston, MA 02115 USA
[13] Harvard Univ, Sch Med, Boston, MA USA
关键词
ORAL ANTICOAGULANT-THERAPY; MOLECULAR-WEIGHT HEPARIN; LONG-TERM; UNFRACTIONATED HEPARIN; ATRIAL-FIBRILLATION; PULMONARY-EMBOLISM; INITIAL TREATMENT; RANDOMIZED-TRIAL; 1ST EPISODE; PREVENTION;
D O I
10.1056/NEJMoa1113697
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Dabigatran, which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism. METHODS In two double-blind, randomized trials, we compared Dabigatran at a dose of 150 mg twice daily with warfarin (active-control study) or with placebo (placebo-control study) in patients with venous thromboembolism who had completed at least 3 initial months of therapy. RESULTS In the active-control study, recurrent venous thromboembolism occurred in 26 of 1430 patients in the Dabigatran group (1.8%) and 18 of 1426 patients in the warfarin group (1.3%) (hazard ratio with Dabigatran, 1.44; 95% confidence interval [CI], 0.78 to 2.64; P = 0.01 for noninferiority). Major bleeding occurred in 13 patients in the Dabigatran group (0.9%) and 25 patients in the warfarin group (1.8%) (hazard ratio, 0.52; 95% CI, 0.27 to 1.02). Major or clinically relevant bleeding was less frequent with Dabigatran (hazard ratio, 0.54; 95% CI, 0.41 to 0.71). Acute coronary syndromes occurred in 13 patients in the Dabigatran group (0.9%) and 3 patients in the warfarin group (0.2%) (P = 0.02). In the placebo-control study, recurrent venous thromboembolism occurred in 3 of 681 patients in the Dabigatran group (0.4%) and 37 of 662 patients in the placebo group (5.6%) (hazard ratio, 0.08; 95% CI, 0.02 to 0.25; P<0.001). Major bleeding occurred in 2 patients in the Dabigatran group (0.3%) and 0 patients in the placebo group. Major or clinically relevant bleeding occurred in 36 patients in the Dabigatran group (5.3%) and 12 patients in the placebo group (1.8%) (hazard ratio, 2.92; 95% CI, 1.52 to 5.60). Acute coronary syndromes occurred in 1 patient each in the Dabigatran and placebo groups. CONCLUSIONS Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinically relevant bleeding than warfarin but a higher risk than placebo. (Funded by Boehringer Ingelheim; RE-MEDY and RE-SONATE ClinicalTrials.gov numbers, NCT00329238 and NCT00558259, respectively.)
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页码:709 / 718
页数:10
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