Meta-Analysis

. 2017 Aug 15;89(7):687-696.

doi: 10.1212/WNL.0000000000004235. Epub 2017 Jul 19.

Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation

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

Affiliations

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.

PMID: 28724590
PMCID: PMC5562962
DOI: 10.1212/WNL.0000000000004235

Meta-Analysis

Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation

Eleni Korompoki et al. Neurology. 2017.

. 2017 Aug 15;89(7):687-696.

doi: 10.1212/WNL.0000000000004235. Epub 2017 Jul 19.

Authors

Affiliations

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.

PMID: 28724590
PMCID: PMC5562962
DOI: 10.1212/WNL.0000000000004235

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.

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Figures

**Figure 1. PRISMA flowchart: Study selection**
AF = atrial fibrillation; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

**Figure 2. Pooled RR meta-analyses for IS that occurred between 6 weeks and 1 year of follow-up after exposure to different treatment strategies**
(A) VKA vs no-VKA, (B) VKA vs APA, (C) VKA vs no-ATM, and (D) APA vs no-ATM. APA = antiplatelet agent; ATM = antithrombotic medication; CI = confidence interval; IS = ischemic stroke; IV = inverse variance; RR = rate ratio; VKA = vitamin K antagonist.

**Figure 3. Pooled RR meta-analyses for ICH recurrence that occurred between 6 weeks and 1 year of follow-up after exposure to different treatment strategies**
(A) VKA vs no-VKA, (B) VKA vs APA, (C) VKA vs no-ATM, and (D) APA vs no-ATM. APA = antiplatelet agent; ATM = antithrombotic medication; CI = confidence interval; ICH = intracranial hemorrhage; IV = inverse variance; RR = rate ratio; VKA = vitamin K antagonist.

See this image and copyright information in PMC

References

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1. Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011;342:d124. - PMC - PubMed
1. Flynn RW, MacDonald TM, Murray GD, Doney AS. Systematic review of observational research studying the long-term use of antithrombotic medicines following intracerebral hemorrhage. Cardiovasc Ther 2010;28:177–184. - PubMed
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1. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010;138:1093–1100. - PubMed

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Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation

Affiliations

Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation

Authors

Affiliations

Abstract

Figures

References

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LinkOut - more resources

Full Text Sources

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Medical

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