Douketis James D, Arneklev Karin, Goldhaber Samuel Z, Spandorfer John, Halperin Frank, Horrow Jay
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Arch Intern Med. 2006 Apr 24;166(8):853-9. doi: 10.1001/archinte.166.8.853.
Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring.
We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0). We determined annual risk of bleeding (any, major), case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment.
Annual incidence of any bleeding was 31.75% with ximelagatran and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2-42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran- and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of major bleeding was higher with warfarin than ximelagatran after 24 months of treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable with both treatments. Risk factors for bleeding with ximelagatran were as follows (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P = .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68; 1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69-3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02).
Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation. Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.
希美加群是一种新型直接凝血酶抑制剂，可采用固定口服剂量给药，无需进行抗凝监测。
我们对心房颤动口服凝血酶抑制剂预防卒中III和V试验中的7329例非瓣膜性心房颤动患者进行了汇总分析，以比较接受每日两次36毫克希美加群或华法林钠（目标国际标准化比值为2.0 - 3.0）治疗的患者的出血结局。我们确定了出血的年度风险（任何出血、大出血）、病死率、大出血的时间进程和解剖部位，以及希美加群和华法林治疗大出血的危险因素。
希美加群治疗的患者任何出血的年度发生率为31.75%，华法林治疗的患者为38.82%（相对风险降低18.2%；95%置信区间[CI]，13.0 - 23.1；P <.001）。希美加群治疗的患者大出血的年度发生率为2.01%，华法林治疗的患者为2.68%（相对风险降低25.1%；95% CI，3.2 - 42.1；P = .03）。希美加群和华法林治疗的患者出血的病死率相当（8.16%对8.09%；P = .98）。治疗24个月后，华法林治疗的患者大出血的累积发生率高于希美加群（4.7%对3.7%；P = .04）。两种治疗的出血解剖部位相当。希美加群出血的危险因素如下（括号内为风险比和95% CI）：糖尿病（1.81；I.19 - 2.77；P = .006）、既往卒中或短暂性脑缺血发作（1.78；1.16 - 2.73；P = .008）、年龄75岁及以上（1.70；1.33 - 2.18；P <.001）以及使用阿司匹林（1.68；1.08 - 2.59；P = .02）。华法林治疗患者出血的危险因素为既往肝病（4.88；1.55 - 15.39；P = .007）、使用阿司匹林（2.41；1.69 - 3.43；P <.001）以及年龄75岁及以上（1.26；1.03 - 1.52；P = .02）。
对于非瓣膜性心房颤动患者，每日两次服用36毫克希美加群治疗的出血风险低于华法林。使用阿司匹林和年龄增加与希美加群和华法林治疗患者的出血风险增加相关。
