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

Abstract

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.

Figure 1

Proportion of propensity‐matched cohort of patients in the Stockholm Creatinine Measurements (SCREAM) cohort initiating or β‐blocker therapy (light gray; N=20 186) or angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker therapy (dark gray; N=20 186) with (A) potassium >5 mmol/L and (B) potassium >5.5 mmol/L during the first year on therapy. ACEi indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate.

Figure 2

Calibration plot of observed vs predicted risk of potassium >5.5 mmol/L in the year following angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker therapy by decile of predicted risk among patients in the (A) Stockholm Creatinine Measurements (SCREAM) development cohort (N=52 544), and (B) Geisinger Health System validation cohort (N=14 772). Reflects patients with baseline potassium levels <5 mmol/L.