From the Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (A.C., R.D.).
Brigham and Women's Hospital, Boston, MA; Research Information Systems and Computing, Partners Healthcare, Boston, MA (V.M.C., V.G., S.M.).
Stroke. 2018 Sep;49(9):2046-2052. doi: 10.1161/STROKEAHA.118.022412.
Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.
背景与目的-抗凝治疗和国际标准化比值(INR)升高对蛛网膜下腔出血后发生动脉瘤破裂的影响尚不清楚。本研究旨在探讨抗凝治疗、INR 升高与颅内动脉瘤破裂之间的关系。方法-我们对马萨诸塞州总医院和布莱根妇女医院 1990 年至 2016 年间诊断的 4696 例颅内动脉瘤患者(6403 个动脉瘤)进行了病例对照研究,包括 1198 例前瞻性患者,这些患者均未接受抗凝治疗或接受华法林抗凝治疗。患者分为破裂组和未破裂组。采用单变量和多变量逻辑回归分析评估抗凝治疗、INR 值和临床表现与颅内动脉瘤破裂之间的关系,并考虑抗凝药物使用与 INR 值之间的交互作用。采用倾向评分进行逆概率加权,以最小化基线人口统计学特征的差异。计算抗凝治疗对不同 INR 值分层下的破裂风险的边际效应。结果-在未加权和加权多变量分析中,未接受抗凝治疗的患者中 INR 值升高与破裂状态显著相关(未加权比值比,22.78;95%置信区间,10.85-47.81;加权比值比,28.16;95%置信区间,12.44-63.77)。在接受抗凝治疗的患者中,当 INR≥1.2 时,华法林的使用与 INR 显著相互作用,降低了 INR 对破裂风险的影响。结论-INR 升高与颅内动脉瘤破裂相关,但华法林可能会调节 INR 对破裂风险的影响。因此,在对颅内动脉瘤患者进行咨询时,应考虑 INR 值。