Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, S-751 85 Uppsala, Sweden.
Eur Heart J. 2011 Nov;32(22):2781-9. doi: 10.1093/eurheartj/ehr113. Epub 2011 May 7.
After an acute coronary syndrome, patients remain at risk of recurrent ischaemic events, despite contemporary treatment, including aspirin and clopidogrel. We evaluated the safety and indicators of efficacy of the novel oral direct thrombin inhibitor dabigatran.
In this double-blind, placebo-controlled, dose-escalation trial, 1861 patients (99.2% on dual antiplatelet treatment) in 161 centres were enrolled at mean 7.5 days (SD 3.8) after an ST-elevation (60%) or non-ST-elevation (40%) myocardial infarction and randomized to twice daily treatment with dabigatran 50 mg (n = 369), 75 mg (n = 368), 110 mg (n = 406), 150 mg (n = 347), or placebo (n = 371). Primary outcome was the composite of major or clinically relevant minor bleeding during the 6-month treatment period. There were 96 primary outcome events and, compared with placebo, a dose-dependent increase with dabigatran, hazard ratio (HR) 1.77 (95% confidence intervals 0.70, 4.50) for 50 mg; HR 2.17 (0.88, 5.31) for 75 mg; HR 3.92 (1.72, 8.95) for 110 mg; and HR 4.27 (1.86, 9.81) for 150 mg. Compared with placebo, D-dimer concentrations were reduced in all dabigatran dose groups by an average of 37 and 45% at weeks 1 and 4, respectively (P< 0.001). Fourteen (3.8%) patients died, had a myocardial infarction or stroke in the placebo group compared with 17 (4.6%) in 50 mg, 18 (4.9%) in 75 mg, 12 (3.0%) in 110 mg, and 12 (3.5%) in the 150 mg dabigatran groups.
Dabigatran, in addition to dual antiplatelet therapy, was associated with a dose-dependent increase in bleeding events and significantly reduced coagulation activity in patients with a recent myocardial infarction.
尽管采用了包括阿司匹林和氯吡格雷在内的当代治疗方法，急性冠状动脉综合征（ACS）后患者仍存在复发性缺血事件的风险。我们评估了新型口服直接凝血酶抑制剂达比加群的安全性和疗效指标。
在这项双盲、安慰剂对照、剂量递增试验中，161 个中心共纳入 1861 例患者（99.2%接受双联抗血小板治疗），平均在 ST 段抬高（60%）或非 ST 段抬高（40%）心肌梗死发生后 7.5 天（标准差 3.8），并随机接受每日两次达比加群 50 mg（n = 369）、75 mg（n = 368）、110 mg（n = 406）、150 mg（n = 347）或安慰剂（n = 371）治疗。主要结局是 6 个月治疗期间主要或临床相关的轻微出血的复合事件。共有 96 例主要结局事件，与安慰剂相比，达比加群组随着剂量的增加而呈剂量依赖性增加，50 mg 的风险比（HR）为 1.77（95%置信区间 0.70，4.50）；75 mg 的 HR 为 2.17（0.88，5.31）；110 mg 的 HR 为 3.92（1.72，8.95）；150 mg 的 HR 为 4.27（1.86，9.81）。与安慰剂相比，所有达比加群组在第 1 周和第 4 周时 D-二聚体浓度平均分别降低 37%和 45%（均 P<0.001）。安慰剂组中有 14 例（3.8%）患者死亡、发生心肌梗死或卒中，而 50 mg 组、75 mg 组、110 mg 组和 150 mg 组分别有 17 例（4.6%）、18 例（4.9%）、12 例（3.0%）和 12 例（3.5%）。
达比加群联合双联抗血小板治疗与出血事件的剂量依赖性增加相关，并显著降低了近期心肌梗死患者的凝血活性。
