Lancet. 1997 Aug 9;350(9075):389-96.
Antiplatelet therapy with aspirin and systematic anticoagulation with warfarin reduce cardiovascular morbidity and mortality after myocardial infarction when given alone. In the Coumadin Aspirin Reinfarction Study (CARS), we aimed to find out whether a combination of low-dose warfarin and low-dose aspirin would give superior results to standard aspirin monotherapy without excessive bleeding risk.
We used a randomised double-blind study design. At 293 sites, we randomly assigned 8803 patients who had had myocardial infarction, treatment with 160 mg aspirin, 3 mg warfarin with 80 mg aspirin, or 1 mg warfarin with 80 mg aspirin. Patients took a single tablet daily, and attended for prothrombin time (PT) measurements at weeks 1, 2, 3, 4, 6, and 12, and then every 3 months. Patients were followed up for a maximum of 33 months (median 14 months).
The primary event was first occurrence of reinfarction, non-fatal ischaemic stroke, or cardiovascular death. 1-year life-table estimates for the primary event were 8.6% (95% CI 7.6-9.6) for 160 mg aspirin, 8.4% (7.4-9.4) for 3 mg warfarin with 80 mg aspirin, and 8.8% (7.6-10) for 1 mg warfarin with 80 mg aspirin. Primary comparisons were done with all follow-up data. The relative risk of the primary event for the 160 mg aspirin group compared with the 3 mg warfarin with 80 mg aspirin group was 0.95 (0.81-1.12, p = 0.57). For spontaneous major haemorrhage (not procedure related), 1-year life-table estimates were 0.74% (0.43-1.1) in the 160 mg aspirin group and 1.4% (0.94-1.8) in the 3 mg warfarin with 80 mg aspirin group (p = 0.014 log rank on follow-up). For the 3382 patients assigned 3 mg warfarin with 80 mg aspirin, the INR results were: at week 1 (n = 2985) median 1.51 (IQR 1.23-2.13); at week 4 (n = 2701) 1.27 (1.13-1.64); at month 6 (n = 2145) 1.19 (1.08-1.44).
Low, fixed-dose warfarin (1 mg or 3 mg) combined with low-dose aspirin (80 mg) in patients who have had myocardial infarction does not provide clinical benefit beyond that achievable with 160 mg aspirin monotherapy.
单独使用阿司匹林进行抗血小板治疗以及使用华法林进行系统性抗凝治疗，可降低心肌梗死后的心血管发病率和死亡率。在“华法林与阿司匹林再梗死研究（CARS）”中，我们旨在确定小剂量华法林与小剂量阿司匹林联合使用是否能在不增加过多出血风险的情况下，比标准阿司匹林单药治疗产生更好的效果。
我们采用随机双盲研究设计。在293个研究地点，我们将8803例心肌梗死患者随机分配，分别给予160毫克阿司匹林、3毫克华法林与80毫克阿司匹林联合治疗，或1毫克华法林与80毫克阿司匹林联合治疗。患者每天服用一片药，并在第1、2、3、4、6和12周，然后每3个月进行一次凝血酶原时间（PT）测量。对患者进行了最长33个月（中位时间14个月）的随访。
主要事件为首次再梗死、非致命性缺血性卒中或心血管死亡。160毫克阿司匹林组1年生命表估计的主要事件发生率为8.6%（95%置信区间7.6 - 9.6），3毫克华法林与80毫克阿司匹林联合治疗组为8.4%（7.4 - 9.4），1毫克华法林与80毫克阿司匹林联合治疗组为8.8%（7.6 - 10）。主要比较采用所有随访数据。160毫克阿司匹林组与3毫克华法林与80毫克阿司匹林联合治疗组相比，主要事件的相对风险为0.95（0.81 - 1.12，p = 0.57）。对于自发性大出血（与手术无关），160毫克阿司匹林组1年生命表估计发生率为0.74%（0.43 - 1.1），3毫克华法林与80毫克阿司匹林联合治疗组为1.4%（0.94 - 1.8）（随访时对数秩检验p = 0.014）。对于分配接受3毫克华法林与80毫克阿司匹林联合治疗的3382例患者，国际标准化比值（INR）结果如下：第1周（n = 2985），中位数为1.51（四分位间距1.23 - 2.13）；第4周（n = 2701），1.27（1.13 - 1.64）；第6个月（n = 2145），1.19（1.08 - 1.44）。
心肌梗死患者使用低剂量固定剂量的华法林（1毫克或3毫克）与低剂量阿司匹林（80毫克）联合治疗，与160毫克阿司匹林单药治疗相比，并未带来更多临床益处。
