Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists

Abstract

Background: Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA-associated hyperkalaemia in real-world settings and the extent of subsequent MRA discontinuation are poorly quantified.

Methods and results: Observational study including all Stockholm citizens initiating MRA therapy during 2007-2010. Hyperkalaemias were identified from all potassium (K⁺ ) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1-year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K⁺ of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K⁺ > 5.0 mmol/L), the majority within the first 3 monthsnthsnthsnthsnths of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity-matched new beta-blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K⁺ > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year.

Conclusion: Among real-world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.

Keywords: Adverse drug events; Heart failure; Renin-angiotensin-aldosterone system inhibitors; Spironolactone.