title: Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program.
abstract: OBJECTIVE
  We explored the incidence and predictors of hyperkalemia in a broad population of heart failure patients.
  
  
  BACKGROUND
  When used in optimal doses to treat patients with heart failure, renin-angiotensin-aldosterone system (RAAS) inhibitors improve clinical outcomes but can cause hyperkalemia.
  
  
  METHODS
  Participants in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) (n = 7,599) Program were randomized to standard heart failure therapy plus candesartan or placebo, titrated as tolerated to a target of 32 mg once daily with recommended monitoring of serum potassium and creatinine. We assessed the incidence and predictors of hyperkalemia associated with dose reduction, study drug discontinuation, hospitalization, or death over the median 3.2 years of follow-up.
  
  
  RESULTS
  Independent of treatment assignment, the risk of hyperkalemia increased with age > or =75 years, male gender, diabetes, creatinine > or =2.0 mg/dl, K+ > or =5.0 mmol/l, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the rate of aggregate hyperkalemia from 1.8% to 5.2% (difference 3.4%, p < 0.0001) and serious hyperkalemia (associated with death or hospitalization) from 1.1% to 1.8% (difference 0.7%, p < 0.001), with hyperkalemia associated with death reported in 2 (0.05%) candesartan patients and 1 (0.03%) placebo patient. The benefit of candesartan in reducing cardiovascular death or heart failure hospitalization (relative risk reduction 16%, p < 0.0001) was uniform in these subgroups, as was the incremental risk of hyperkalemia.
  
  
  CONCLUSIONS
  The risk of hyperkalemia is increased in symptomatic heart failure patients with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, or combined RAAS blockade. Although these groups derive incremental clinical benefit from candesartan, careful surveillance of serum potassium and creatinine is particularly important.
authors.affiliation: Department of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. adesai@partners.org
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dunlap
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: James W
authors.initials: JW
authors.lastname: Hainer
authors.forename: Bertil
authors.initials: B
authors.lastname: Olofsson
authors.forename: Eric L
authors.initials: EL
authors.lastname: Michelson
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D006947:Hyperkalemia / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality; D015994:Incidence; D008297:Male; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan