title: Protocol for Cerebral Microbleeds during the Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin Therapy in Stroke Patients with Nonvalvular Atrial Fibrillation (CMB-NOW) Study: Multisite Pilot Trial.
abstract: BACKGROUND
  Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non-vitamin K antagonist oral anticoagulants (NOACs).
  
  
  OBJECTIVE
  This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs.
  
  
  METHODS
  We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging (T2(∗)-weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke.
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan. Electronic address: shun@is.icc.u-tokai.ac.jp.
authors.forename: Shunya
authors.initials: S
authors.lastname: Takizawa
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Department of Neurology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nishiyama
authors.affiliation: Department of Neurology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nagata
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizuma
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yutani
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Diagnostic Radiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Noriharu
authors.initials: N
authors.lastname: Yanagimachi
authors.affiliation: Department of Diagnostic Radiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D002543:Cerebral Hemorrhage / Q000209:etiology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D010865:Pilot Projects; D020521:Stroke / Q000150:complications / Q000188:drug therapy; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects; D015337:Multicenter Studies as Topic; D064887:Observational Studies as Topic
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Acute ischemic stroke; MRI; NOACs; anticoagulant; cerebral microbleeds; warfarin