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

Background: Potassium-sparing diuretics (KSDs) and renin-angiotensin system (RAS) agents (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARBs]) are commonly prescribed for the management of hypertension, cardiovascular diseases, and diabetic nephropathy. However, there is a concern of developing hyperkalemia when these drugs are concomitantly used. This study investigates the change in serum potassium during concomitant administration of RAS agents (ACEI or ARB) and KSD. Methods: This is a retrospective observational study using the Cerner Health Facts database. Electronic health records from unique patient hospitalization encounters were used to compare change in the serum potassium among 5 different cohorts (ACEI, ARB, KSD, ACEI-KSD, and ARB-KSD) and a non-RAS non-KSD exposed one (acetaminophen [APAP] cohort). Descriptive data of the cohorts and the risk of increase in potassium serum were estimated by generalized linear regression. Results: A total of 5816 patients’ unique encounters were analyzed. After admission, 5.2% (N = 303) had serum potassium greater than 5.5 mmol/L. Results showed a significant increase in serum potassium during concomitant use of KSD and RAS agents and when only using KSD compared with the control APAP group (all P < 0.05). Other significant predictors of increased serum potassium levels included male (P = 0.002), black race (P < 0.001), and individuals with low estimated glomerular filtration rate (P < 0.001). Conclusions: 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.