Impact of hyperkalaemia on renin-angiotensin-aldosterone (RAAS) inhibitor reduction or withdrawal following hospitalisation

Clin Exp Med. 2024 Dec 21;25(1):16. doi: 10.1007/s10238-024-01531-9.

Abstract

Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.

Methods: This was a retrospective cohort study of adult patients hospitalised from 1 January2017 to 31 December2020. Biochemistry data, clinical notes and medicines use were extracted using the CogStack platform, from electronic health records. Patients were identified by creatinine measurement during hospitalisation. Hyperkalaemia was defined as potassium > 5.0 mmol/L, with severity categorisation. RAASi discontinuation defined as ≥ 48 h without administration. Mortality risk associated with RAASi cessation was assessed using Cox proportional hazards models.

Results: Among 129,172 patients with potassium measurements, 49,011 were hospitalised. Hyperkalaemia prevalence was 8.57% in the emergency department and 16.79% among hospitalised patients. Higher hyperkalaemia levels correlated with increased CKD and heart failure. RAASi use was more common in hyperkalaemic patients, with higher discontinuation rates during hospitalisation (36% with potassium 5-5.5 mmol/L; 61% with potassium > 6.5 mmol/L). By discharge, 32% of patients had RAASi stopped, and 2% doses reduced. Discontinuation of RAASi was associated with 37% worse survival probability.

Conclusion: RAASi cessation was greater with hyperkalaemia and associated with increased mortality in hospitalised patients. Reinstitution of RAASi after hospital discharge, or alternative management of hyperkalaemia if maintained on RAASi therapy, may improve clinical outcomes.

Keywords: ACE inhibitors; Hyperkalaemia; Mortality; Renin–angiotensin system.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists* / adverse effects
  • Angiotensin Receptor Antagonists* / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors* / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Female
  • Heart Failure / drug therapy
  • Heart Failure / mortality
  • Hospitalization* / statistics & numerical data
  • Humans
  • Hyperkalemia* / blood
  • Hyperkalemia* / chemically induced
  • Hypertension / drug therapy
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Potassium / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / mortality
  • Renin-Angiotensin System / drug effects
  • Retrospective Studies

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Potassium