Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program

J Am Coll Cardiol. 2007 Nov 13;50(20):1959-66. doi: 10.1016/j.jacc.2007.07.067. Epub 2007 Oct 29.


Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds
  • Female
  • Follow-Up Studies
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology*
  • Heart Failure / mortality
  • Humans
  • Hyperkalemia / drug therapy*
  • Hyperkalemia / epidemiology*
  • Hyperkalemia / mortality
  • Incidence
  • Male
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Factors
  • Tetrazoles / therapeutic use*


  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • candesartan