Incident hyperkalemia may be an independent therapeutic target in low ejection fraction heart failure patients: insights from the HEAAL study

Int J Cardiol. 2014 May 15;173(3):380-7. doi: 10.1016/j.ijcard.2014.02.034. Epub 2014 Feb 28.


Background: Angiotensin receptor antagonists (ARBs) improve outcomes in patients with heart failure (HF) with reduced left ventricular ejection fraction, but may induce hyperkalemia (HK) and/or a worsening of renal function (WRF).

Methods and results: The incidence and risk factors of HK and its inter-relationship with WRF, as well as associations with clinical outcome (death or admission for HF i.e. the primary outcome) in 3846 HF patients enrolled in the double blind HEAAL trial (losartan 150 mg/d vs. 50 mg/d) were assessed. Worsening of renal function was defined as a decrease in eGFR >20% from baseline and HK as serum K >5.5 or >5 mmol/L. Higher dose of losartan increased serum potassium. Episodes of HK >5 mmol/L or WRF occurred at least once in about half of the patients. WRF was associated with higher occurrence of HK (HR 1.19 (1.06-1.34)) and vice versa (HR 1.35 (1.19-1.53)), but preceded HK in only about half of the events. High dose losartan improved outcome despite more frequent WRF and HK, both being independently associated with adverse outcomes in multivariate analyses.

Conclusions: HK and WRF are common in HF patients. Both can be predicted from baseline risk factors and are therefore potentially preventable. Although associated with worse outcome, occurrence of any does not hinder the efficacy of high dose losartan. HK was associated with WRF and worse outcomes. Whether therapy targeting specifically HK may maximize the survival benefit derived from renin angiotensin aldosterone inhibitor use should be appropriately tested in future trials.

Keywords: Heart failure; Hyperkalemia; Losartan; Renal insufficiency.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / administration & dosage*
  • Double-Blind Method
  • Drug Delivery Systems / methods
  • Female
  • Follow-Up Studies
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology*
  • Humans
  • Hyperkalemia / diagnosis
  • Hyperkalemia / drug therapy*
  • Hyperkalemia / epidemiology*
  • Incidence
  • Internationality
  • Losartan / administration & dosage
  • Male
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / drug therapy
  • Renal Insufficiency / epidemiology
  • Risk Factors
  • Stroke Volume / drug effects
  • Stroke Volume / physiology*


  • Angiotensin II Type 1 Receptor Blockers
  • Losartan