title: Quality of Vitamin K Antagonist Control and 1-Year Outcomes in Patients with Atrial Fibrillation: A Global Perspective from the GARFIELD-AF Registry.
abstract: OBJECTIVE
  Vitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0-3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality.
  
  
  RESULTS
  TTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027).
  
  
  CONCLUSIONS
  A large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01090362.
authors: Formerly Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors: Sylvia
authors: S
authors: Haas
authors: Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
authors: Hugo
authors: H
authors: Ten Cate
authors: Thrombosis Research Institute, London, United Kingdom.
authors: Gabriele
authors: G
authors: Accetta
authors: Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Pantep
authors: P
authors: Angchaisuksiri
authors: Thrombosis Research Institute, London, United Kingdom.|Department of Cardiology, EA 3920, University of Besançon, Besançon, France.
authors: Jean-Pierre
authors: JP
authors: Bassand
authors: Division of Cardiovascular Sciences, St George's University of London, London, United Kingdom.
authors: A John
authors: AJ
authors: Camm
authors: Department of Cardiology, Catholic University School of Medicine, Santiago, Chile.
authors: Ramon
authors: R
authors: Corbalan
authors: Department of Cardiology, Vascular Medicine and Intensive Care Medicine, Vivantes Neukoelln Medical Centre, Berlin, Germany.
authors: Harald
authors: H
authors: Darius
authors: Department of Primary Care Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors: David A
authors: DA
authors: Fitzmaurice
authors: Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors: Samuel Z
authors: SZ
authors: Goldhaber
authors: Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Japan.
authors: Shinya
authors: S
authors: Goto
authors: Department of Hematology and Molecular Medicine, Johannesburg Hospital, University of the Witwatersrand, Johannesburg, South Africa.
authors: Barry
authors: B
authors: Jacobson
authors: Thrombosis Research Institute, London, United Kingdom.
authors: Gloria
authors: G
authors: Kayani
authors: Center for Public Health Research (CESP), University of Milano-Bicocca, Milan, Italy.
authors: Lorenzo G
authors: LG
authors: Mantovani
authors: Bayer Pharma AG, Berlin, Germany.
authors: Frank
authors: F
authors: Misselwitz
authors: Duke Clinical Research Institute, Durham, NC, United States of America.
authors: Karen
authors: K
authors: Pieper
authors: Internal Medicine, Dresden-Friedrichstadt Hospital, Dresden, Germany.
authors: Sebastian M
authors: SM
authors: Schellong
authors: Intensive Cardiac Therapy Clinic, Institute of Cardiology, Warsaw, Poland.
authors: Janina
authors: J
authors: Stepinska
authors: Department of Medicine, McMaster University, Hamilton, Canada.
authors: Alexander G G
authors: AG
authors: Turpie
authors: Bayer Pharma AG, Berlin, Germany.
authors: Martin
authors: M
authors: van Eickels
authors: Thrombosis Research Institute, London, United Kingdom.|University College London, London, United Kingdom.
authors: Ajay K
authors: AK
authors: Kakkar
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000980:Antiplatyhelmintic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D000980:Antiplatyhelmintic Agents; D014812:Vitamin K