Hyperkalemia After Initiating Renin-Angiotensin System Blockade: The Stockholm Creatinine Measurements (SCREAM) Project

J Am Heart Assoc. 2017 Jul 19;6(7):e005428. doi: 10.1161/JAHA.116.005428.


Background: Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score.

Methods and results: We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new β-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β-blocker and ACE-I/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m2 were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration.

Conclusions: Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m2, but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.

Keywords: angiotensin receptor blockers; angiotensin‐converting enzyme inhibition; angiotensin‐converting enzyme inhibitors; chronic kidney disease; hyperkalemia; potassium; risk score.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Biomarkers / blood
  • Creatinine / blood*
  • Databases, Factual
  • Drug Monitoring / methods*
  • Drug Monitoring / standards
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hyperkalemia / blood*
  • Hyperkalemia / chemically induced*
  • Hyperkalemia / diagnosis
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Logistic Models
  • Male
  • Middle Aged
  • Potassium / blood*
  • Predictive Value of Tests
  • Propensity Score
  • Renin-Angiotensin System / drug effects*
  • Reproducibility of Results
  • Risk Factors
  • Sweden
  • Time Factors
  • Treatment Outcome


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Creatinine
  • Potassium