Context: In patients with nonvalvular atrial fibrillation,warfarin prevents is chemic stroke, but dose adjustment,coagulation monitoring, and bleeding limit it s use. Objective:To compare the efficacy of the oral dire...Context: In patients with nonvalvular atrial fibrillation,warfarin prevents is chemic stroke, but dose adjustment,coagulation monitoring, and bleeding limit it s use. Objective:To compare the efficacy of the oral direct thrombin in-hibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Desi gn, Setting, and Participants: Double-blind, randomized, multicenter trial(2000 -2001) conducted at 409 North American sites, involving 3922 patients with nonv alvular atrial fibrillation and additional stroke risk factors. Interventions Ad justed dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures: The primary endpoint was all strokes (ischemic or hemorrhagic) and systemicembo lic events. The primary analysis was based on demonstrating noninferiority withi n an absolute margin of 2.0%per year according to the intention-to-treat mode l.Results: During 6405 patient-years (mean 20 months) of follow-up, 88 patient s experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was wi thin target during 68%of the treatment period. The primary event rate with xime lagatran was 1.6%per year and with warfarin was 1.2 %per year (absolute differ ence, 0.45%per year; 95%confidence interval, -0.13%to 1.03%per year; P<.001 for the predefined noninferiority hypothesis).When all-cause mortality was inc luded in addition to stroke and systemic embolic events, the rate difference was 0.10%per year (95%confidence interval, -0.97%to1.2%per year; P = .86). The re was no difference between treatment groups in rates of major bleeding, but to tal bleeding (major and minor) was lower with ximelagatran (37%vs 47%per year; 95%confidence interval for the difference,-14%to -6.0%per year; P < .001). Serum alanine aminotransferase levels rose to greater than 3 times the upper li mit of normal in 6.0%of patients treated with ximelagatran,usually within 6 mon ths and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other sug gestive case occurred. Conclusions: The results establish the efficacy of fixe d-dose oral ximelagatran without coagulation monitoring compared with well-con trolled warfarin for prevention of thromboembolism in patients with atrial fibri llation requiring chronic anticoagulant therapy, but the potential for hepatotox icity requires further investigation.展开更多
Context: In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. Objective: To compare the efficacy of the oral dir...Context: In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. Objective: To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Design, Setting, and Participants: Double-blind, randomized, multicenter trial(2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Interventions Adjusted dose warfarin(aiming for an international normalized ratio[INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures: The primary end point was all strokes(ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0%per year according to the intention-to-treat model. Results: During 6405 patient-years(mean 20 months) of follow-up, 88 patients experienced primary events. The mean(SD) INR with warfarin(2.4[0.8]) was within target during 68%of the treatment period. The primary event rate with ximelagatran was 1.6%per year and with warfarin was 1.2 %per year(absolute difference, 0.45%per year; 95%confidence interval,-0.13%to 1.03%per year; P< .001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10%per year(95%confidence interval,-0.97%to 1.2%per year; P=.86). There was no difference between treatment groups in rates of major bleeding, but total bleeding(major and minor) was lower with ximelagatran(37%vs 47%per year; 95%confidence interval for the difference,-14%to-6.0%per year; P< .001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0%of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. Conclusions: The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.展开更多
文摘Context: In patients with nonvalvular atrial fibrillation,warfarin prevents is chemic stroke, but dose adjustment,coagulation monitoring, and bleeding limit it s use. Objective:To compare the efficacy of the oral direct thrombin in-hibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Desi gn, Setting, and Participants: Double-blind, randomized, multicenter trial(2000 -2001) conducted at 409 North American sites, involving 3922 patients with nonv alvular atrial fibrillation and additional stroke risk factors. Interventions Ad justed dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures: The primary endpoint was all strokes (ischemic or hemorrhagic) and systemicembo lic events. The primary analysis was based on demonstrating noninferiority withi n an absolute margin of 2.0%per year according to the intention-to-treat mode l.Results: During 6405 patient-years (mean 20 months) of follow-up, 88 patient s experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was wi thin target during 68%of the treatment period. The primary event rate with xime lagatran was 1.6%per year and with warfarin was 1.2 %per year (absolute differ ence, 0.45%per year; 95%confidence interval, -0.13%to 1.03%per year; P<.001 for the predefined noninferiority hypothesis).When all-cause mortality was inc luded in addition to stroke and systemic embolic events, the rate difference was 0.10%per year (95%confidence interval, -0.97%to1.2%per year; P = .86). The re was no difference between treatment groups in rates of major bleeding, but to tal bleeding (major and minor) was lower with ximelagatran (37%vs 47%per year; 95%confidence interval for the difference,-14%to -6.0%per year; P < .001). Serum alanine aminotransferase levels rose to greater than 3 times the upper li mit of normal in 6.0%of patients treated with ximelagatran,usually within 6 mon ths and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other sug gestive case occurred. Conclusions: The results establish the efficacy of fixe d-dose oral ximelagatran without coagulation monitoring compared with well-con trolled warfarin for prevention of thromboembolism in patients with atrial fibri llation requiring chronic anticoagulant therapy, but the potential for hepatotox icity requires further investigation.
文摘Context: In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. Objective: To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Design, Setting, and Participants: Double-blind, randomized, multicenter trial(2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Interventions Adjusted dose warfarin(aiming for an international normalized ratio[INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures: The primary end point was all strokes(ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0%per year according to the intention-to-treat model. Results: During 6405 patient-years(mean 20 months) of follow-up, 88 patients experienced primary events. The mean(SD) INR with warfarin(2.4[0.8]) was within target during 68%of the treatment period. The primary event rate with ximelagatran was 1.6%per year and with warfarin was 1.2 %per year(absolute difference, 0.45%per year; 95%confidence interval,-0.13%to 1.03%per year; P< .001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10%per year(95%confidence interval,-0.97%to 1.2%per year; P=.86). There was no difference between treatment groups in rates of major bleeding, but total bleeding(major and minor) was lower with ximelagatran(37%vs 47%per year; 95%confidence interval for the difference,-14%to-6.0%per year; P< .001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0%of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. Conclusions: The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.
