title: Hyperkalemia and renal function during monotherapy and dual renin-angiotensin blockade in the community setting.
abstract: BACKGROUND
  In controlled trials, dual therapy with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) is associated with hyperkalemia and decreased renal function, but there is no information about these adverse effects in clinical practice.
  
  
  OBJECTIVE
  The aim of this study was to assess the incidence of hyperkalemia and decreased renal function during dual therapy (ACE-I plus ARB) in a community-based setting.
  
  
  METHODS
  In a retrospective cohort database study, we identified patients who received ARBs added to ongoing ACE-I therapy and who had at least 1 measurement of serum creatinine and potassium during each treatment period. We compared rates of hyperkalemia (>5.5 mmol/L) during equal periods of monotherapy and dual therapy and the rate of a significant rise in serum creatinine (≥0.5 mg/dL) between study periods. We assessed the impact of potential confounders on outcomes by logistic regression analysis.
  
  
  RESULTS
  Among 425 patients (median follow-up 19 months for each treatment period), hyperkalemia was 2-fold more common during dual therapy than monotherapy (11.1% and 5.6% of patients, respectively) (relative risk = 1.96; 95% CI, 1.22-3.14; P < 0.001). In 77 patients with reduced renal function on monotherapy (serum creatinine ≥1.5 mg/dL), the rate of hyperkalemia was 20.8/100 patient-years, resulting in a number needed to harm of 10.1 patients, compared with 52.6 patients among those with preserved renal function. Mean serum creatinine between treatment periods increased >0.5 mg/dL in 7.5% of patients, more commonly in patients with decreased (18.2%) than with preserved (5.2%) baseline renal function (P < 0.001).
  
  
  CONCLUSIONS
  In the community setting, dual therapy was associated with hyperkalemia and a decrease in renal function. The absolute risks were especially high among patients with reduced baseline renal function.
authors.affiliation: Department of Pharmaceutics and Clinical Pharmacology, Medical Division, Maccabi Healthcare Services, Israel. kurnik_d@mac.org.il
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
authors.forename: Janet
authors.initials: J
authors.lastname: Vesterman-Landes
authors.forename: Martin
authors.initials: M
authors.lastname: Bialik
authors.forename: Itzhak
authors.initials: I
authors.lastname: Katzir
authors.forename: Yosef
authors.initials: Y
authors.lastname: Lomnicky
authors.forename: Hillel
authors.initials: H
authors.lastname: Halkin
authors.forename: Ronen
authors.initials: R
authors.lastname: Loebstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced* / Q000453:epidemiology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects; D012189:Retrospective Studies
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D003404:Creatinine