title: Antihypertensive medication exposure and cardiovascular outcomes in hemodialysis patients.
abstract: OBJECTIVE
  Our understanding of the effectiveness of cardioprotective medications in maintenance dialysis patients is based upon drug exposures assessed at a single point in time. We employed a novel, time-dependent approach to modeling medication use over time to examine outcomes in a large national cohort.
  
  
  METHODS
  We linked Medicaid prescription claims with United States Renal Data System registry data and Medicare claims for 52,922 hypertensive maintenance dialysis patients. All-cause mortality and a combined cardiovascular disease (CVD)-endpoint were modeled as functions of exposure to cardioprotective antihypertensive medications (renin angiotensin system antagonists, β-adrenergic blockers, and calcium channel blockers) measured with three time-dependent covariates (weekly exposure status, proportion of prior weeks with exposure, and number of switches in exposure status) and with propensity adjustment.
  
  
  RESULTS
  Current cardioprotective medication exposure status as compared to not exposed was associated with lower adjusted hazard ratios (AHRs) for mortality, though the magnitude depended upon the proportion of prior weeks with medication (duration) and the number of switches between active and non-active use (switches) (AHR range 0.54-0.90). Combined CVD-endpoints depended upon the proportion of weeks on medication: AHR = 1.18 for 10% and AHR = 0.90 for 90% of weeks. Combined CVD-endpoint was also lower for patients with fewer switches.
  
  
  CONCLUSIONS
  Effectiveness depends not only on having a drug available but is tempered by duration and stability of use, likely reflecting variation in clinical stability and patient behavior.
authors.affiliation: Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kans., USA.
authors.forename: Theresa I
authors.initials: TI
authors.lastname: Shireman
authors.forename: Milind A
authors.initials: MA
authors.lastname: Phadnis
authors.forename: James B
authors.initials: JB
authors.lastname: Wetmore
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhou
authors.forename: Sally K
authors.initials: SK
authors.lastname: Rigler
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.forename: Edward F
authors.initials: EF
authors.lastname: Ellerbeck
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Mahnken
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology / Q000401:mortality*; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008484:Medicaid / Q000706:statistics & numerical data; D006278:Medicare / Q000706:statistics & numerical data; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D016491:Peripheral Vascular Diseases / Q000453:epidemiology; D012042:Registries; D006435:Renal Dialysis; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology / Q000401:mortality*; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers