OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

2nd Department of Neurology AHEPA University Hospital Aristotle University of Thessaloniki Thessaloniki Greece

2nd Department of Neurology Attikon University Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece

Advanced Arrhythmia Therapeutic Branch Division of Cardiology Saiseikai Kumamoto Hospital Cardiovascular Center Kumamoto Japan

CEDOC Nova Medical School New University of Lisbon Lisbon Portugal

Centre for Clinical Brain Sciences School of Clinical Sciences University of Edinburgh Edinburgh United Kingdom

Department of Cardiology and Department of Hypertension and Stroke Medicine Hirosaki University Graduate School of Medicine Hirosaki Japan

Department of Clinical Neurosciences and Mental Health Faculty of Medicine University of Porto Porto Portugal

Department of Medicine and Neurology at Royal Melbourne Hospital University of Melbourne Parkville Victoria Australia

Department of Neurology and General Internal Medicine Tokyo Saiseikai Central Hospital Tokyo Japan

Department of Neurology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA

Department of Neurology Braga Hospital Braga Portugal

Department of Neurology Centro Hospitalar e Universitário de Coimbra Coimbra Portugal

Department of Neurology Christchurch Hospital Christchurch New Zealand

Department of Neurology Democritus University of Thrace Alexandroupolis Greece

Department of Neurology Donders Institute for Brain Cognition and Behavior Radboud University Medical Center Nijmegen the Netherlands

Department of Neurology Dresden Neurovascular Center Dresden Germany

Department of Neurology Heidelberg University Hospital Heidelberg Germany

Department of Neurology Helsinki University Hospital Helsinki Finland

Department of Neurology Henry Ford Hospital Detroit MI

Department of Neurology Lille University INSERM U1171 Degenerative and Vascular Cognitive Disorders CHU Lille Lille France

Department of Neurology Maastricht University Medical Center Maastricht the Netherlands

Department of Neurology São João University Hospital Center Porto Portugal

Department of Neurology School of Medicine University of Crete Crete Greece

Department of Neurology St Josef Hospital Ruhr University Bochum Bochum Germany

Department of Neurology University of Ioannina School of Medicine Ioannina Greece

Department of Neurology University of Tennessee Health Science Center Memphis TN

Department of Neurology University of Thessaly Larissa Greece

Department of Neurosciences Eastern Health Melbourne Victoria Australia

Department of Neurosurgery Georg August University of Göttingen Göttingen Germany

Department of Research and Development Tachikawa Medical Center Nagaoka Japan

Department of Statistical Science University College London London United Kingdom

Division of Brain Sciences Department of Stroke Medicine Imperial College London United Kingdom

Division of Cardiovascular Sciences School of Medical Sciences University of Manchester Manchester Academic Health Science Centre Manchester United Kingdom

Division of Neurology Department of Internal Medicine Faculty of Medicine Saga University Saga Japan

Division of Neurology Yong Loo Lin School of Medicine National University of Singapore Singapore

Faculty of Medicine University of Coimbra Coimbra Portugal

Hirosaki Stroke and Rehabilitation Center Hirosaki Japan

International Clinical Research Center and Neurology Department St Anne's Hospital and Masaryk University Brno Czech Republic

Neurology Department Egas Moniz Hospital West Lisbon Hospital Center Lisbon Portugal

Neuroradiological Academic Unit Department of Brain Repair and Rehabilitation Institute of Neurology University College London London United Kingdom

Neurorehabilitation Unit University of Basel and University Center for Medicine of Aging Felix Platter Hospital Basel Switzerland

Ottawa Hospital Research Institute and University of Ottawa Ottawa Ontario Canada

Stroke Center and Department of Neurology National Taiwan University Hospital Taiwan

Stroke Center and Neurology University Hospital and University of Basel Basel Switzerland

Stroke Research Centre Department of Brain Repair and Rehabilitation University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London United Kingdom New Zealand Brain Research Institute Christchurch New Zealand

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