Changes in serum potassium with concomitant administration of renin-angiotensin system agents and potassium-sparing diuretics: U.S. cohort study using electronic health record data

Potassium sparing diuretics (KSD) and, renin-angiotensin system (RAS) agents [including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB)] are commonly prescribed for the management of hypertension, cardiovascular diseases, and in diabetic nephropathy. However, there is a concern of developing hyperkalemia when these drugs are concomitantly use. This study investigates the change in serum potassium when concomitant administration of RAS agents (ACEI/ARB) and KSD. Retrospective observational study using the CERNER Health Facts® (HF) database. Electronic health records from unique patient hospitalization encounters were used to compare change in the serum potassium among five different cohorts: ACEI, ARB, KSD, ACEI-KSD and ARB-KSD and a non-RAS non-KSD exposed one (acetaminophen cohort). Descriptive on the cohorts and the risk for increase in potassium serum was estimated by generalized linear regression. A total of 5,816 patients’ unique encounters were analyzed. Following admission 5.2% (N=303) had serum potassium >5.5 mmol/L. Results showed a significant increase in serum potassium when concomitant use of KSD and RAS agents and when only using KSD compared to the control acetaminophen group (all p <0.05). Other significant predictors of increased serum potassium levels included male (p=0.002), African American race (p=<0.001), and individuals with low estimated glomerular filtration rate (p=<0.001). This study found no evidence of hyperkalemia when combining KSD and other medications that may increase potassium levels, even when controlling for other potential factors that may affect serum potassium levels, for patients within institutional settings. Warnings concerning excessive potassium levels when a KSD is prescribed with a medication that may affect potassium should be limited to patients with pre-existing higher levels of potassium.