FC 024SAFETY AND EFFICACY OF PATIROMER FOR HYPERKALAEMIA IN PATIENTS WITH STAGE 1-3A OR STAGE 3B-5 CHRONIC KIDNEY DISEASE: POOLED ANALYSIS OF THE AMETHYST-DN, OPAL-HK AND TOURMALINE TRIALS
Authors: Haller Hermann , Bianchi Stefano , McCafferty Kieran , Arthur Susan , Wegmann Liliana-Georgiana , Budden Jeffery , Weir Matthew 
Published: May 2021

Abstract

Background and Aims
In patients with CKD and/or heart failure (HF), hyperkalaemia (HK) is a major problem which limits the use of guideline-recommended renin–angiotensin–aldosterone inhibitors (RAASi). Dose reduction or cessation of RAASi therapy results in increased morbidity and mortality. Improved strategies to mitigate HK are required to improve clinical outcomes. Patiromer is a non-absorbed, sodium-free, K+ binder that has been shown to reduce serum K+ in patients with HK, and thereby enable RAASi therapy. We conducted a post-hoc analysis to evaluate patiromer’s efficacy and safety in two HK subgroups by CKD severity: patients with Stage 3b-5 CKD and those with Stage 1-3a.

Method
Data were combined from the initial 4 weeks of treatment of three studies (AMETHYST-DN, OPAL-HK and TOURMALINE). Eligible patients had a diagnosis of CKD and HK (local laboratory serum K+ &gt;5.0 mmol/L) and received patiromer 8.4 to 33.6 g/day to start. Subgroups were identified by baseline estimated glomerular filtration rate (eGFR): stage 3b–5 (severe/end-stage CKD) and stage 1–3a (mild/moderate CKD). The efficacy population comprised randomised patients who received ≥1 dose patiromer and had ≥1 post-baseline serum K+ assessment available. Efficacy was evaluated as the mean (± standard error [SE]) change in central laboratory serum K+ from baseline to Week 4 (primary endpoint in AMETHYST-DN and OPAL-HK; secondary endpoint in TOURMALINE). Safety outcomes, including incidence and severity of adverse events (AEs) with onset during the 4-week evaluation period, were assessed in all randomised patients who received ≥1 dose of patiromer.

Results
Of the 626 patients evaluable for efficacy, 61.8% were male, mean±standard deviation (SD) age was 65.6±9.8 years and 417 (66.6%) had stage 3b-5 CKD, including 27 (6.5%) patients with stage 5 CKD. Approximately 34% of patients in both subgroups had HF, predominantly NYHA Class II. Baseline characteristics were similar between the stage 3b–5 and stage 1–3a CKD subgroups, except for serum K+ (mean±SD: 5.47±0.41 and 5.32±0.42 mmol/L, respectively), eGFR (mean±SD: 27.9±9.0 and 58.0±12.8 mL/min/1.73m2), and spot urine albumin:creatinine ratio (mean±SD: 1263±1921 and 606±1241 mg/g). In total, 91.8% of patients with stage 3b-5 CKD and 97.6% of patients with stage 1-3a CKD were receiving RAASi therapy at baseline. Patiromer induced early reductions in serum K+, with mean levels decreasing from baseline to below 5.0 mmol/L by Day 3 or Week 1 in the stage 3b–5 and stage 1–3a CKD subgroups, respectively (Figure). The mean change in serum K+ from baseline to Week 4 was −0.84±0.03 and −0.60±0.04 mmol/L in patients with stage 3b–5 and stage 1–3a CKD, respectively. Overall, 96.4% and 99.0% of patients with stage 3b–5 and stage 1–3a CKD, respectively, achieved normokalaemia (≥1 serum K+ value 3.8–5.0 mEq/L) during the 4 weeks of treatment. In total, 421 patients with CKD stage 3b–5 and 211 with CKD stage 1–3a were evaluable for safety. AEs were reported by 168 (39.9%) and 58 (27.5%) patients with stage 3b–5 and stage 1–3a CKD, respectively. The most frequent AEs in stage 3b–5 and stage 1–3a CKD patients, respectively, were constipation (7.8% and 2.8%) and diarrhoea (4.0% and 1.9%); all cases were mild or moderate in severity. AEs leading to patiromer discontinuation occurred in 5.7% and 2.4% of stage 3b–5 CKD and stage 1–3a CKD patients, respectively.

Conclusion
This pooled analysis of three clinical trials clearly demonstrated the efficacy of patiromer to effectively treat HK in patients with CKD, regardless of early or advanced disease, the majority of whom were receiving guideline-recommended RAASi blockade. Patiromer was well tolerated with mild gastrointestinal events in a small percentage of patients, and very few discontinuations. Patiromer is an appropriate choice for the control of HK in patients with CKD stage 3b–5.