Joan Martí-Fàbregas1, Santiago Medrano-Martorell2, Elisa Merino2, Luis Prats-Sánchez2, Rebeca Marín2, Raquel Delgado-Mederos2, Alejandro Martínez-Domeño2, Pol Camps-Renom2, Elena Jiménez-Xarrié2, Mariluisa Zedde2, Manuel Gómez-Choco2, Lidia Lara2, Amèlia Boix2, Ana Calleja2, Ana María De Arce-Borda2, Yolanda Bravo2, Blanca Fuentes2, María Hernández-Pérez2, David Cánovas2, Laura Llull2, Beatriz Zandio2, Marimar Freijo2, Ignacio Casado-Naranjo2, Jordi Sanahuja2, Dolores Cocho2, Jerzy Krupinski2, Ana Rodríguez-Campello2, Ernest Palomeras2, Alicia De Felipe2, Marta Serrano2, Elena Zapata-Arriaza2, Josep Zaragoza-Brunet2, Inmaculada Díaz-Maroto2, Jessica Fernández-Domínguez2, Aida Lago2, José Maestre2, Manuel Rodríguez-Yáñez2, Ignasi Gich2. 1. 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. jmarti@santpau.cat. 2. 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.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 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). CONCLUSION: 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. CLINICALTRIALSGOV IDENTIFIER: NCT02238470.
OBJECTIVE: 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. METHODS: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. RESULTS: 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, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 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). CONCLUSION: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. CLINICALTRIALSGOV IDENTIFIER: NCT02238470.
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