Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized Trials

Abstract

Background: Hyperkalemia is a common electrolyte abnormality in patients with chronic kidney disease (CKD), which is associated with worse outcomes and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi). This post hoc subgroup analysis of three clinical trials evaluated the efficacy and safety of the sodium-free, potassium-binding polymer, patiromer, for the treatment of hyperkalemia in adults with non-dialysis CKD. Methods: Data from the 4-week treatment periods of AMETHYST-DN, OPAL-HK, and TOURMALINE studies were combined. Patients had baseline diagnosis of CKD, hyperkalemia (serum potassium >5.0 mEq/L) and received patiromer 8.4-33.6 g/day. Patients were stratified by baseline estimated glomerular filtration rate (eGFR) into two subgroups: severe/end-stage CKD (Stage 3b-5; eGFR<45 mL/min/1.73m2) and mild/moderate CKD (Stage 1-3a; eGFR ≥45 mL/min/1.73m2). Efficacy was assessed by the change in serum potassium (mean±standard error [SE]) from baseline to week 4. Safety assessments included incidence and severity of adverse events (AEs). Results: Efficacy analyses (N=626; 62% male, mean age 66 years) included 417 (67%) patients with severe/end-stage CKD and 209 (33%) with mild/moderate CKD. Most patients were receiving RAASi therapy at baseline (severe/end-stage CKD: 92%; mild/moderate CKD: 98%). The mean±SE change in serum potassium (baseline to week 4) was −0.84±0.03 in the severe/end-stage CKD subgroup, and −0.60±0.04 mEq/L in the mild/moderate CKD subgroup. AEs were reported for 40% and 27% patients in the severe/end-stage and mild/moderate CKD subgroups, respectively, with 16% and 12% reporting AEs considered related to patiromer. The most frequent AEs were mild-to-moderate constipation (8% and 3%) and diarrhea (4% and 2%). AEs leading to patiromer discontinuation occurred in 6% and 2% of patients with severe/end-stage CKD, and mild/moderate CKD, respectively. Conclusions: Patiromer was effective for treatment of hyperkalemia and well tolerated in patients across stages of CKD, most of whom were receiving guideline-recommended RAASi therapy.