Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, Pfeffer M, Hohnloser S, Yusuf S
Health Research Institute, Hamilton, ON, Canada.
Lancet. 2006 Jun 10;367(9526):1903-12. doi: 10.1016/S0140-6736(06)68845-4.
Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.
Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.
The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).
Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.
口服抗凝治疗可降低房颤患者发生血管事件的风险。然而，长期监测是必要的，且许多患者无法实现最佳抗凝效果。我们评估了氯吡格雷联合阿司匹林在预防血管事件方面是否不劣于口服抗凝治疗。
入选患有房颤且伴有一项或多项卒中危险因素的患者，并将其随机分配接受口服抗凝治疗（目标国际标准化比值为2.0 - 3.0；n = 3371）或氯吡格雷（每日75毫克）联合阿司匹林（推荐每日75 - 100毫克；n = 3335）。结局事件由一个盲法委员会判定。主要结局是首次发生卒中、非中枢神经系统系统性栓塞、心肌梗死或血管性死亡。分析采用意向性治疗。本研究已在ClinicalTrials.gov注册，编号为NCT00243178。
由于有明确证据表明口服抗凝治疗更具优势，该研究提前终止。接受口服抗凝治疗的患者中有165例发生主要事件（年风险3.93%），接受氯吡格雷联合阿司匹林治疗的患者中有234例（年风险5.60%；相对风险1.44（1.18 - 1.76；p = 0.0003）。在研究开始时就已接受口服抗凝治疗的患者，与在研究开始时未接受该治疗的患者相比，血管事件减少趋势更明显（相对风险1.50，95%可信区间1.19 - 1.89），且口服抗凝治疗的大出血风险显著更低（分别为1.30；0.94 - 1.79和1.27，0.85 - 1.89以及0.59，0.32 - 1.08；交互作用p = 0.03）。
对于卒中高危的房颤患者，口服抗凝治疗在预防血管事件方面优于氯吡格雷联合阿司匹林，尤其是在那些已经接受口服抗凝治疗的患者中。
