Eleni Korompoki1, Filippos T Filippidis1, Peter B Nielsen1, Angela Del Giudice1, Gregory Y H Lip1, Joji B Kuramatsu1, Hagen B Huttner1, Jiming Fang1, Sam Schulman1, Joan Martí-Fàbregas1, Celine S Gathier1, Anand Viswanathan1, Alessandro Biffi1, Daniela Poli1, Christian Weimar1, Uwe Malzahn1, Peter Heuschmann1, Roland Veltkamp2. 1. From the Division of Brain Sciences (E.K., A.D.G., R.V.), Department of Stroke Medicine, and Department of Primary Care and Public Health (F.T.F.), Imperial College, London, UK; Aalborg Thrombosis Research Unit (P.B.N., G.Y.H.L.), Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Denmark; Institute of Cardiovascular Sciences (G.Y.H.L.), University of Birmingham, UK; Department of Neurology (J.B.K., H.B.H.), University of Erlangen-Nuremberg, Erlangen, Germany; Institute for Clinical Evaluative Sciences (J.F.), Toronto; Thrombosis and Atherosclerosis Research Institute (S.S.), Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Stroke Unit (J.M.-F.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; Department of Neurology and Neurosurgery (C.S.G.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neurology (A.V., A.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Thrombosis Center (D.P.), Careggi Hospital, Florence, Italy; Department of Neurology (C.W.), University Hospital of Duisburg-Essen, Essen; Clinical Trial Center Würzburg (U.M., P.H.), University Hospital Würzburg; and Institute of Clinical Epidemiology and Biometry (P.H.), Comprehensive Heart Failure Center, University Würzburg, Germany. 2. From the Division of Brain Sciences (E.K., A.D.G., R.V.), Department of Stroke Medicine, and Department of Primary Care and Public Health (F.T.F.), Imperial College, London, UK; Aalborg Thrombosis Research Unit (P.B.N., G.Y.H.L.), Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Denmark; Institute of Cardiovascular Sciences (G.Y.H.L.), University of Birmingham, UK; Department of Neurology (J.B.K., H.B.H.), University of Erlangen-Nuremberg, Erlangen, Germany; Institute for Clinical Evaluative Sciences (J.F.), Toronto; Thrombosis and Atherosclerosis Research Institute (S.S.), Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Stroke Unit (J.M.-F.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; Department of Neurology and Neurosurgery (C.S.G.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neurology (A.V., A.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Thrombosis Center (D.P.), Careggi Hospital, Florence, Italy; Department of Neurology (C.W.), University Hospital of Duisburg-Essen, Essen; Clinical Trial Center Würzburg (U.M., P.H.), University Hospital Würzburg; and Institute of Clinical Epidemiology and Biometry (P.H.), Comprehensive Heart Failure Center, University Würzburg, Germany. r.veltkamp@imperial.ac.uk.
Abstract
OBJECTIVE: To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up. METHODS: A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method. RESULTS: Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29-0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79-2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45-1.90, p = 0.84). CONCLUSIONS: In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.
OBJECTIVE: To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up. METHODS: A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method. RESULTS: Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29-0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79-2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45-1.90, p = 0.84). CONCLUSIONS: In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.
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