Hylek E M, Skates S J, Sheehan M A, Singer D E
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
N Engl J Med. 1996 Aug 22;335(8):540-6. doi: 10.1056/NEJM199608223350802.
To avert major hemorrhage, physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation. Since the low rate of stroke has made it difficult to perform prospective studies to resolve this issue, we conducted a case-control study.
We studied 74 consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin. For each patient with stroke, three controls with nonrheumatic atrial fibrillation who were treated as outpatients were randomly selected from the 1994 registry of the anticoagulant-therapy unit (222 controls). We used the international normalized ratio (INR) to measure the intensity of anticoagulation. For the patients with stroke, we used INR at admission; for the controls, we selected the INR that was measured closest to the month and day of the matched case patient's hospital admission.
The risk of stroke rose steeply at INRs below 2.0. At an INR of 1.7, the adjusted odds ratio for stroke, as compared with the risk at an INR of 2.0, was 2.0 (95 percent confidence interval, 1.6 to 2.4); at an INR of 1.5, it was 3.3 (95 percent confidence interval, 2.4 to 4.6); and at an INR of 1.3, it was 6.0 (95 percent confidence interval, 3.6 to 9.8). Other independent risk factors were previous stroke (odds ratio, 10.4; 95 percent confidence interval, 4.4 to 24.5), diabetes mellitus (odds ratio, 2.95; 95 percent confidence interval, 1.3 to 6.5), hypertension (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 5.7), and current smoking (odds ratio, 5.7; 95 percent confidence interval, 1.4 to 24.0).
Among patients with atrial fibrillation, anticoagulant prophylaxis is effective at INRs of 2.0 or greater. Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0, tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower, less effective levels of anticoagulation.
为避免严重出血，医生需要了解在预防心房颤动患者中风方面有效的最低抗凝强度。由于中风发生率较低，难以开展前瞻性研究来解决这一问题，我们进行了一项病例对照研究。
我们研究了1989年至1994年间连续74例因缺血性中风入院且正在服用华法林的心房颤动患者。对于每例中风患者，从抗凝治疗单元1994年登记册中随机选取3例非风湿性心房颤动门诊患者作为对照（共222例对照）。我们使用国际标准化比值（INR）来衡量抗凝强度。对于中风患者，我们采用入院时的INR值；对于对照患者，我们选取最接近匹配病例患者入院月份和日期所测量的INR值。
INR低于2.0时，中风风险急剧上升。INR为1.7时，与INR为2.0时的风险相比，中风的校正比值比为2.0（95%置信区间为1.6至2.4）；INR为1.5时，校正比值比为3.3（95%置信区间为2.4至4.6）；INR为1.3时，校正比值比为6.0（95%置信区间为3.6至9.8）。其他独立危险因素包括既往中风（比值比为10.4；95%置信区间为4.4至24.5）、糖尿病（比值比为2.95；95%置信区间为1.3至6.5）、高血压（比值比为2.5；95%置信区间为1.1至5.7）以及当前吸烟（比值比为5.7；置信区间为1.4至24.0）。
在心房颤动患者中，抗凝预防在INR为2.0或更高时有效。由于既往研究表明，INR大于4.0至5.0时出血风险迅速上升，因此严格控制抗凝治疗以使INR维持在2.0至3.0之间，比将抗凝水平设定得更低且效果不佳的策略更好。
