From the Department of Neurology (J.M.-F., L.P.-S., R.M., R.D.-M., A.M.-D., P.C.-R., E.J.-X.) and Epidemiology (I.G.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute, Barcelona; Departments of Radiology (S.M.-M.) and Neurology (A.R.-C.), Hospital del Mar-Parc de Salut Mar, Barcelona; Unitat RM IDI (E.M.) and Department of Neurosciences (M.H.-P.), Hospital Germans Trias i Pujol, Badalona; Department of Neurology (M.Z.), Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy; Department of Neurology (M.G.-C.), Hospital de Sant Joan Despí Moises Broggi, Sant Joan Despí, Spain; Department of Neurology (L. Lara), Hospital de León; Department of Neurology (A.B.), Hospital Universitari Son Espases, Palma de Mallorca; Department of Neurology (A.C.), Hospital de Valladolid; Department of Neurology (A.M.D.A.-B.), Hospital de Donostia; Department of Neurology (Y.B.), Hospital de Burgos; Department of Neurology (B.F.), Hospital Universitario La Paz, Universidad Autónoma de Madrid, Instituto de Investigación IdiPaz, Madrid; Department of Neurology (D. Cánovas), Hospital Parc Taulí, Sabadell; Department of Neurology (L. Llull), Hospital Clínic, Barcelona; Department of Neurology (B.Z.), Hospital de Navarra, Pamplona; Department of Neurology (M.F.), Hospital de Basurto, Bilbao; Department of Neurology (I.C.-N.), Hospital San Pedro de Alcántara, Cáceres; Department of Neurology (J.S.), Hospital Arnau de Vilanova, Lleida; Department of Neurology (D. Cocho), Hospital de Granollers; Department of Neurology (J.K.), F.Ass. Mutua Terrassa; Department of Neurology (E.P.), Hospital de Mataró; Department of Neurology (A.D.F.), Hospital Ramón y Cajal, Madrid; Department of Neurology (M.S.), Hospital La Rioja, Logroño; Department of Neurology (E.Z.-A.), Hospital Virgen del Rocío, Sevilla; Department of Neurology (J.Z.-B.), Hospital Verge de la Cinta, Tortosa; Department of Neurology (I.D.-M.), Hospital de Albacete; Department of Neurology (J.F.-D.), Centro Médico Asturias, Oviedo; Department of Neurology (A.L.), Hospital La Fe, Valencia; Department of Neurology (J.M.), Hospital Virgen de las Nieves, Granada; and Department of Neurology (M.R.-Y.), Hospital Santiago de Compostela, Santiago de Compostela, Spain.
Neurology. 2019 May 21;92(21):e2432-e2443. doi: 10.1212/WNL.0000000000007532. Epub 2019 Apr 19.
We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.
Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.
We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4).
Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.
NCT02238470.
我们通过基线 MRI 评估易出血性脑动脉病变的替代标志物，检测口服抗凝剂（OAs）治疗的心源性栓塞性缺血性脑卒中患者颅内出血（ICH）的风险，验证这一假说。
患者参加了一项多中心前瞻性观察研究。他们年龄大于 64 岁，患有近期心源性栓塞性缺血性脑卒中，且为 OA 的新使用者。他们接受基线 MRI 分析，以评估微出血、脑白质高信号和皮质表面铁沉积。我们收集了人口统计学变量、临床特征、风险评分和治疗数据。主要终点为随访期间发生的 ICH。我们进行了双变量和多变量 Cox 回归分析。
共纳入 937 例患者（年龄 77.6 ± 6.5 岁，47.9%为男性）。207 例（22.5%）患者检测到微出血，419 例（45.1%）患者检测到中重度脑白质高信号，28 例（3%）患者检测到皮质表面铁沉积。平均随访 23.1 ± 6.8 个月后，18 例（1.9%）患者发生 ICH。多变量分析显示，微出血（风险比 2.7，95%置信区间[CI]1.1-7， = 0.034）和中重度脑白质高信号（风险比 5.7，95% CI 1.6-20， = 0.006）与 ICH 相关（C 指数 0.76，95% CI 0.66-0.85）。同时存在微出血和中重度脑白质高信号的患者 ICH 发生率最高（每 100 患者年 3.76 例，95% CI 1.62-7.4）。
服用 OAs 的患者存在 advanced cerebral small vessel disease，表现为微出血和中重度脑白质高信号，ICH 风险增加。我们的研究结果有助于确定为心源性脑卒中患者开具 OA 处方的风险。
临床试验.gov 标识符：NCT02238470。
