title: Adherence and variability in warfarin dose requirements: assessment in a prospective cohort.
abstract: OBJECTIVE
  Although several genetic and nongenetic factors are associated with warfarin dose, approximately 40% of variability remains unexplained. An as yet unexplored factor is medication adherence. Here, we investigate the influence of adherence on response to warfarin and on pharmacogenetic analyses of association.
  
  
  METHODS
  A total of 311 patients starting warfarin were followed-up prospectively, and adherence was measured at 1, 8 and 26 weeks. The association between adherence and warfarin response was tested, and the additional proportion of variability in response explained by adherence was assessed.
  
  
  RESULTS
  Significant associations were found between adherence and achievement of stable dose and time taken to achieve it, with nonadherers taking longer. Adjusting for adherence increased the proportion of explained variability in treatment response by up to 8%.
  
  
  CONCLUSIONS
  Given the significant contribution of adherence to drug response, we recommend that consideration is given to the value of assessing adherence when designing future pharmacogenetic studies of warfarin and other drugs.
authors: Department of Biostatistics, University of Liverpool, Shelley's Cottage, Brownlow Street, Liverpool, L69 3GS, UK. aljorgen@liv.ac.uk
authors: Andrea L
authors: AL
authors: Jorgensen
authors: Dyfrig A
authors: DA
authors: Hughes
authors: Anita
authors: A
authors: Hanson
authors: Diane
authors: D
authors: van Eker
authors: Cheng Hock
authors: CH
authors: Toh
authors: Munir
authors: M
authors: Pirmohamed
authors: Paula R
authors: PR
authors: Williamson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D000925:Anticoagulants; D014859:Warfarin