Effect of patiromer on serum potassium in hyperkalemic patients with heart failure: Pooled analysis of 3 randomized trials.

BACKGROUND: Hyperkalemia (HK) is a serious medical condition that can cause potentially fatal cardiac arrhythmias. Patients with heart failure (HF) are at risk of HK due to underlying chronic kidney disease and use of guideline-recommended renin-angiotensin-aldosterone system inhibitors. Patiromer, a sodium-free, non-absorbed potassium (K+) binder, is indicated for the treatment of HK. OBJECTIVE: To evaluate the consistency of patiromer's effect on lowering serum K+ in patients with HF and HK using pooled data from three clinical trials. METHODS: This post-hoc analysis evaluated the efficacy and safety of patiromer for management of HK over a 4-week treatment period using combined data from three clinical trials (AMETHYST-DN, OPAL-HK and TOURMALINE). Eligible patients had HK (serum K+ > 5.0 mEq/L) at study entry. Starting doses of patiromer ranged from 8.4 to 33.6 g/day. In this analysis, efficacy was assessed as the mean (± standard error [SE]) change in serum K+ from baseline to Week 4. Safety outcomes evaluated included the incidence and severity of adverse events (AEs) during the 4-week treatment period. RESULTS: In total, 653 patients who received ≥1 dose of patiromer were evaluable for efficacy (214 diagnosed with HF and 439 without HF). Mean baseline serum K+ was 5.4 mEq/L. Patient characteristics were generally similar between the HF and non-HF subgroups. Serum K+ decreased to <5.0mEq/L within one week of patients starting patiromer, reaching a nadir after 3 weeks in both the HF and non-HF subgroups (4.59 mEq/L and 4.64 mEq/L, respectively). The mean ±â€¯SE change from baseline to Week 4 in serum K+ was -0.79 ±â€¯0.06 mEq/L (95% CI: -0.91, -0.68) in patients with HF and - 0.75 ±â€¯0.02 mEq/L (95% CI: -0.79, -0.70) in patients without HF. AEs occurred in 31% of patients with HF and 37% of patients without HF and were mostly mild or moderate in severity. The most common AEs were constipation (HF patients: 7%, non-HF patients: 5%) and diarrhea (HF patients: 2%, non-HF patients: 4%). AEs leading to discontinuation of patiromer occurred in 7% of patients with HF and in 3% of patients without HF. CONCLUSIONS: In this pooled analysis of patients with HK, patiromer was generally well tolerated and reduced serum K+ similarly in patients with and without HF over 4 weeks.

Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure.

AIMS: The AMBER trial demonstrated that concomitant use of patiromer enabled the more persistent use of spironolactone by reducing the risk of hyperkalaemia in patients with resistant hypertension and advanced chronic kidney disease. We report herein the pre-specified subgroup analysis in patients with heart failure (HF). METHODS AND RESULTS: Participants were randomly assigned (1:1) to receive either placebo or patiromer (8.4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Dose titrations were permitted after 1 week for patiromer/placebo and after 3 weeks for spironolactone. The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomized patients (intention to treat). A total of 295 patients were enrolled, of whom 132 (45%) had HF. In the HF subgroup, 68.1% of patients receiving placebo remained on spironolactone at week 12, compared with 84.1% of patients receiving patiromer (P = 0.0504). The reason for discontinuation from spironolactone use was hyperkalaemia in the majority of both groups. There was no significant interaction between the subgroups with HF and without HF (P = 0.8085) for the primary endpoint. CONCLUSIONS: Consistent with the overall AMBER trial results, this pre-specified subgroup analysis in patients with HF, resistant hypertension and advanced chronic kidney disease demonstrated that patiromer enabled more persistent use of spironolactone by reducing the risk of hyperkalaemia.