Potassium binders and continuation of renin-angiotensin system inhibitors/mineralocorticoid receptor antagonist in chronic kidney disease and heart failure (the DEMONSTRATE database).

Abstract

Hyperkalaemia is a serious complication in patients with chronic kidney disease (CKD) and heart failure (HF), often leading to the discontinuation of renin-angiotensin-aldosterone system inhibitors (RAASi; renin-angiotensin system inhibitors [RASi] and mineralocorticoid receptor antagonists [MRAs]) despite their cardiorenal benefits. Although potassium binders, especially second-generation potassium binders, reduce the risk of hyperkalaemia in clinical trials, real-world evidence on whether they enable RAASi continuation and influence clinical outcomes remains scarce. This observational, population-based cohort study used Swedish healthcare data from the DEMONSTRATE database to identify adults with non-dialysis (ND) CKD and/or HF who initiated potassium binders (2018-2022). Patients were stratified by potassium binder generation. RASi and MRA treatment changes were assessed at 6 months, and clinical outcomes (all-cause mortality, hospitalization and three-point major adverse cardiovascular events [3P-MACE]) were evaluated over a 3-year follow-up using propensity-score-weighted Kaplan-Meier analyses. Of 7913 potassium binder episodes (6232 patients), 7.1% used second-generation binders. These episodes were associated with increased RAASi persistence at 6 months: 76.9% and 57.5% of second-generation users maintained RASi and MRA therapy, respectively, compared with 66.4% and 47.8% in the first-generation group. Patients who maintained RASi had lower observed all-cause mortality and hospitalization rates, but no difference in incidence of 3P-MACE was found. Second-generation potassium binders were associated with higher RAASi persistence than first-generation binders. RASi persistence was associated with lower observed rates of all-cause mortality and hospitalization, with no clear differences in 3P-MACE. These findings suggest that potassium binders may enable sustained RAASi use in patients with ND-CKD and/or HF.