title: The safety of combining angiotensin-converting-enzyme inhibitors with angiotensin-receptor blockers in elderly patients: a population-based longitudinal analysis.
abstract: BACKGROUND
  The risks associated with using an angiotensin-converting-enzyme (ACE) inhibitor and an angiotensin-receptor blocker together are unclear. This study was designed to determine the safety of combination therapy with these two drugs in clinical practice.
  
  
  METHODS
  We conducted a population-based longitudinal analysis using linked administrative and laboratory data for elderly patients who were new users of an ACE inhibitor, an angiotensin-receptor blocker or a combination of both medications between May 1, 2002, and Dec. 31, 2006. We compared outcomes in patients given combination therapy versus patients given monotherapy using Cox proportional hazards analyses with adjustment for baseline characteristics.
  
  
  RESULTS
  Of the 32,312 new users of either medication (mean age 76.1 years, median creatinine level 92 μmol/L), 1750 (5.4%) received combination therapy. However, 1512 (86.4%) of the patients who were given combination therapy did not have trial-established indications such as heart failure or proteinuria. Renal dysfunction was more common among patients given combination therapy (5.2 [95% confidence interval (CI) 3.4 to 7.9] events per 1000 patients per month) than among patients given monotherapy (2.4 [95% CI 2.2 to 2.7] events per 1000 patients per month) (adjusted hazard ratio [HR] 2.36, 95% CI 1.51 to 3.71). Hyperkalemia was also more common among patients given combination therapy (2.5 [95% CI 1.4 to 4.3] events per 1000 patients per month) than among patients given monotherapy (0.9 [95% CI 0.8 to 1.0] events per 1000 patients per month) (adjusted HR 2.42, 95% CI 1.36 to 4.32). Most patients took combination therapy for only a short time (median three months before at least one agent was stopped).
  
  
  CONCLUSIONS
  Combination therapy was frequently prescribed for patients without established indications and was associated with an increased risk of adverse renal outcomes when compared with monotherapy. These results mirrored data from randomized controlled trials.
authors.affiliation: Division of General Internal Medicine and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alta. finlay.mcalister@ualberta.ca
authors.forename: Finlay A
authors.initials: FA
authors.lastname: McAlister
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.forename: Scott
authors.initials: S
authors.lastname: Klarenbach
authors.forename: Braden J
authors.initials: BJ
authors.lastname: Manns
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D008137:Longitudinal Studies; D008297:Male; D018579:Patient Selection; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors