title: Ischemic stroke and intracranial hemorrhage with aspirin, dabigatran, and warfarin: impact of quality of anticoagulation control.
abstract: OBJECTIVE
  Little is known about the impact of quality of anticoagulation control, as reflected by time in therapeutic range (TTR), on the effectiveness and safety of warfarin therapy in Chinese patients with atrial fibrillation. We investigated the risks of ischemic stroke and intracranial hemorrhage (ICH) in relation to warfarin at various TTRs in a real-world cohort of Chinese patients with atrial fibrillation receiving warfarin and compared with those on dabigatran, aspirin, and no therapy.
  
  
  METHODS
  This is an observational study.
  
  
  RESULTS
  Of 8754 Chinese patients with atrial fibrillation and CHA2DS2-VASc ≥1 (79.5±9.2 years; CHA2DS2-VASc, 4.1±1.5; and Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly (>65 years), Drugs/Alcohol Concomitantly [HAS-BLED], 2.2±0.9), 16.3% received warfarin, 41.1% aspirin, 4.5% dabigatran, and 38.1% received no therapy. The incidence of ischemic stroke was highest in patients with no therapy (10.38%/y), followed by patients on aspirin (7.95%/y). The incidence of stroke decreased progressively with increasing TTR quartiles (<17.9%, 17.9%-38.8%, 38.8%-56.2%, and >56.2%) from 7.34%/y (first quartile) to 3.10%/y (fourth quartile). Patients on dabigatran had the lowest incidence of stroke among all groups (2.24%/y). The incidence of ICH was lowest in patients on dabigatran (0.32%/y) compared with those on warfarin (0.90%/y), aspirin (0.80%/y), and no therapy (0.53%/y). ICH incidence decreased with increasing TTR from 1.37%/y (first quartile) to 0.74%/y (fourth quartile).
  
  
  CONCLUSIONS
  In Chinese patients with atrial fibrillation, the benefits of warfarin therapy for stroke prevention and ICH risk are closely dependent on the quality of anticoagulation, as reflected by TTR. Even at the top TTR quartile, warfarin was associated with a higher stroke and ICH risk than dabigatran.
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Ho
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Mei-Han
authors.initials: MH
authors.lastname: Ho
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Pak-Hei
authors.initials: PH
authors.lastname: Chan
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Jo-Jo
authors.initials: JJ
authors.lastname: Hai
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cheung
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Chun-Yip
authors.initials: CY
authors.lastname: Yeung
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Kui-Kai
authors.initials: KK
authors.lastname: Lau
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Koon-Ho
authors.initials: KH
authors.lastname: Chan
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Gilberto Ka-Kit
authors.initials: GK
authors.lastname: Leung
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.).
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: From the Cardiology Division (C.-W.H., M.-H.H., P.-H.C., J.-J.H., E.C., C.-P.L., H.-F.T., C.-W.S.), Endocrinology Division (C.-Y.Y.), and Neurology Division (K.-K.L., K.-H.C.), Department of Medicine, Queen Mary Hospital and Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine (G.K.-K.L.), University of Hong Kong, Hong Kong SAR, China; and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, University Department of Medicine, Birmingham, United Kingdom (G.Y.H.L.). cwdsiu@hku.hk.
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001562:Benzimidazoles / Q000009:adverse effects*; D002681:China; D015331:Cohort Studies; D000069604:Dabigatran; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014859:Warfarin / Q000009:adverse effects*; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D010975:Platelet Aggregation Inhibitors; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran; D001241:Aspirin
keywords: atrial fibrillation; intracranial hemorrhages