title: The patterns of anticoagulation control and the risk of stroke, bleeding and mortality in patients with non-valvular atrial fibrillation.
abstract: BACKGROUND
  Anticoagulation control is often summarized using the percentage of time spent in a therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR).
  
  
  OBJECTIVE
  To evaluate whether the TTR method can be improved by considering the patterns of INR over time.
  
  
  METHODS
  The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case-control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR.
  
  
  RESULTS
  A number of 27 381 patients were studied with a mean age of 73 years. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03-4.68) in patients with < 30% TTR compared with patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27-13.85) and stroke (OR 3.42, 95% CI 2.08-5.63). INR measures that predicted death independent of the TTR-included absolute difference between two subsequent INR measurements and change relative to the mean over time.
  
  
  CONCLUSIONS
  Cluster analysis of INR patterns improved the prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Van Den Ham
authors.forename: O H
authors.initials: OH
authors.lastname: Klungel
authors.forename: H G M
authors.initials: HG
authors.lastname: Leufkens
authors.forename: T P
authors.initials: TP
authors.lastname: Van Staa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D001777:Blood Coagulation / Q000187:drug effects*; D016022:Case-Control Studies; D016000:Cluster Analysis; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D006801:Humans; D019934:International Normalized Ratio; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000925:Anticoagulants