title: Impact of Non-Adherence on Renal and Cardiovascular Outcomes in US Veterans.
abstract: BACKGROUND
  Adherence is paramount in treating hypertension; however, no gold standard method is available for non-adherence screening, delineating high-risk patients. An International Classification of Diseases 9th Edition non-adherence diagnostic code (V15.81) has been available for decades; but, its utility is poorly studied. We examined the association between the V15.81 code assigned prior to the initiation of anti-hypertensive drugs (AHDs) and renal and cardiovascular outcomes.
  
  
  METHODS
  This was a historical prospective cohort study involving 312,489 newly treated hypertensive individuals (mean age 53.8 years, 90.9% males, 20.3% black, median follow-up 8.0 years). We used crude and Cox models adjusted for baseline socio-demographic characteristics, estimated glomerular filtration rate (eGFR), body mass index, blood pressure, comorbidities, and prospective AHD adherence (measured as proportion of days covered, PDC).
  
  
  RESULTS
  In the unadjusted analysis, the V15.81 code was associated with higher risks for faster eGFR decline (hazard ratio, HR 1.22, 95% CI 1.11-1.33), incident CKD (HR 1.17, 95% CI 1.09-1.27), end-stage renal disease (ESRD) (HR 2.53, 95% CI 1.72-3.72), incident coronary artery disease (CAD) (HR 1.26, 95% CI 1.15-1.38), and stroke (HR 1.55, 95% CI 1.38-1.73). In the adjusted model, the V15.81 code remained predictive of increased risk of CKD (HR 1.33, 95% CI 1.22-1.45), ESRD (HR 1.81, 95% CI 1.18-2.78), incident CAD (HR 1.26, 95% CI 1.14-1.40), and stroke (HR 1.46, 95% CI 1.29-1.65). Additional adjustment for PDC did not alter adverse associations between V15.81 code and studied outcomes.
  
  
  CONCLUSIONS
  Assignment of V15.81 code prior to AHD therapy was associated with higher risks of renal and cardiovascular outcomes in incident hypertensive US veterans. Previous history of non-adherence is a poor prognostic marker in hypertensive individuals; therefore, patients with V15.81 code may require close monitoring. The observational nature of this study limits our ability to make firm recommendations for clinical practice.
authors.affiliation: Division of Nephrology, University of California, Irvine, Calif., USA.
authors.forename: Elvira O
authors.initials: EO
authors.lastname: Gosmanova
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: Ahmed
authors.initials: A
authors.lastname: Alrifai
authors.forename: Jun L
authors.initials: JL
authors.lastname: Lu
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000378:metabolism; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data*; D016903:Drug Monitoring
chemical_list: D000959:Antihypertensive Agents