Hylek Elaine M, Go Alan S, Chang Yuchiao, Jensvold Nancy G, Henault Lori E, Selby Joe V, Singer Daniel E
General Medicine Division, Clinical Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
N Engl J Med. 2003 Sep 11;349(11):1019-26. doi: 10.1056/NEJMoa022913.
The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR.
We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files.
Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0.
Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation.
口服抗凝治疗可大幅降低心房颤动患者的中风发生率，在国际标准化比值（INR）达到2.0或更高时可看到充分疗效。口服抗凝强度对心房颤动相关中风严重程度的影响尚不清楚，但这是选择目标INR的核心问题。
我们研究了13559例非瓣膜性心房颤动患者队列中的缺血性中风事件。通过住院数据库识别中风，并根据病历进行验证，病历还提供了华法林或阿司匹林的使用情况、入院时的INR以及并存疾病的信息。根据改良Rankin量表对中风严重程度进行分级。从住院和死亡档案中确定30天死亡率。
在596例缺血性中风中，32%发生在华法林治疗期间，27%发生在阿司匹林治疗期间，42%在两种治疗都未进行期间发生。在服用华法林的患者中，在比例优势逻辑回归模型中，入院时INR小于2.0与INR为2.0或更高相比，在三个严重程度类别中独立增加了严重中风的几率（优势比，1.9；95%置信区间，1.1至3.4）以及30天内死亡风险（风险比，3.4；95%置信区间，1.1至10.1）。入院时INR为1.5至1.9的死亡率与INR小于1.5的死亡率相似（分别为18%和15%）。中风时服用阿司匹林的患者30天死亡率与服用华法林且INR小于2.0的患者相似。
在非瓣膜性心房颤动患者中，使INR达到2.0或更高的抗凝治疗不仅可降低缺血性中风的发生率，还可降低其严重程度和中风死亡风险。我们的研究结果为反对在心房颤动患者中使用较低INR目标水平提供了进一步证据。
