Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease

Abstract

Aims: Hyperkalaemia risk precludes optimal renin-angiotensin-aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium-free, non-absorbed potassium (K⁺ )-binding polymer approved for the treatment of hyperkalaemia. In PEARL-HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by individualized titration in preventing hyperkalaemia and hypokalaemia when initiating spironolactone.

Methods and results: This open-label 8-week study enrolled 63 patients with CKD, serum K⁺ 4.3-5.1 mEq/L, and chronic HF, who, based on investigator opinion, should receive spironolactone. Eligible patients started spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with patiromer titrated to maintain serum K⁺ 4.0-5.1 mEq/L. Mean (standard deviation) serum K⁺ was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48-4.70 mEq/L during treatment. Serum K⁺ of 3.5-5.5 mEq/L at the end of study treatment (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K⁺ 4.0-5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%) developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all patients; 43 (68%) patients required one or more patiromer dose titration. Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of discontinuations [four (6.3%) patients]. The most common AE was mild to moderate abdominal discomfort [four (6.3%) patients].

Conclusions: In this open-label study, patiromer 16.8 g/day followed by individualized titration maintained serum K⁺ within the target range in the majority of patients with HF and CKD, all of whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated, with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia.

Trial registration: ClinicalTrials.gov NCT01130597.

Keywords: Chronic kidney disease; Heart failure; Mineralocorticoid receptor antagonist; Patiromer; Potassium-binding polymer.

Figure 1

Proportion of patients with serum K⁺ in the range of 3.5–5.5 mEq/L and 4.0–5.1 mEq/L by study visit. ET, end of treatment; K⁺, potassium.

Figure 2

Serum K⁺ before and after an uptitration or downtitration. *Total number of titrations during the study. K⁺, potassium; SD, standard deviation.