Fang Margaret C, Chang Yuchiao, Hylek Elaine M, Rosand Jonathan, Greenberg Steven M, Go Alan S, Singer Daniel E
Division of General Internal Medicine, Hospitalist Group, University of California, San Francisco, San Francisco 94143, USA.
Ann Intern Med. 2004 Nov 16;141(10):745-52. doi: 10.7326/0003-4819-141-10-200411160-00005.
The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity.
To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage.
Case-control study.
Academic medical center.
170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation.
The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use.
Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2]).
Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder.
The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.
低抗凝强度时，房颤相关性卒中风险增加。然而，较高强度会增加出血风险。华法林用于房颤的最佳使用需要依据患者年龄和抗凝强度，精确了解颅内出血风险。
研究年龄、抗凝强度与颅内出血风险之间的关系。
病例对照研究。
学术医疗中心。
170例在华法林治疗期间发生颅内出血的病例患者及1020例匹配的未发生颅内出血的对照患者；病例患者和对照患者均因房颤服用华法林。
作者进行多变量条件逻辑回归分析，以确定年龄和国际标准化比值（INR）相关的颅内出血几率，同时控制合并症和阿司匹林使用情况。
病例患者年龄大于对照患者（中位年龄，78岁对75岁；P<0.001），且中位INR更高（2.7对2.3；P<0.001）。85岁及以上时颅内出血风险增加（校正比值比，2.5[95%CI，1.3至4.7]；参照年龄，70至74岁），INR范围为3.5至3.9时风险也增加（校正比值比，4.6[CI，2.3至9.4]；参照INR，2.0至3.0）。INR小于2.0时的颅内出血风险与INR为2.0至3.0时的风险无统计学差异（校正比值比，1.3[CI，0.8至2.2]）。
尽管在其他研究中抗凝持续时间与出血有关，但本研究无法控制这一潜在混杂因素。
85岁时颅内出血风险增加。与INR在2.0至3.0之间相比，INR小于2.0与较低的颅内出血风险无关。因此，抗凝管理应着重将INR维持在2.0至3.0范围内，即使是老年房颤患者，而非将目标INR设定为小于2.0。同样，应避免INR达到或超过3.5。
