Long-term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin-converting enzymes/angiotensin receptor blockers: results from AMETHYST-DN

Abstract

Aims: Chronic kidney disease (CKD) in heart failure (HF) increases the risk of hyperkalaemia (HK), limiting angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) use. Patiromer is a sodium-free, non-absorbed potassium binder approved for HK treatment. We retrospectively evaluated patiromer's long-term safety and efficacy in HF patients from AMETHYST-DN.

Methods and results: Patients with Type 2 diabetes, CKD, and HK [baseline serum potassium >5.0-5.5 mmol/L (mild) or >5.5-<6.0 mmol/L (moderate)], with or without HF (New York Heart Association Class I and II, by investigator judgement), on ACE-I/ARB, were randomized to patiromer 8.4-33.6 g to start, divided twice daily. Overall, 105/304 (35%) patients had HF (75%, Class II). Mean (standard deviation) ejection fraction (EF) was 44.9% (8.2) (n = 81) in patients with HF; 26 had EF ≤40%. In HF patients, mean serum potassium decreased by Day 3 through Week 52. At Week 4, estimated mean (95% confidence interval) change in serum potassium was -0.64 mmol/L (-0.72, -0.55) in mild and -0.97 mmol/L (-1.14, -0.80) in moderate HK (both P < 0.0001). Most HF patients with mild (>88%) and moderate (≥73%) HK had normokalaemia at each visit from Weeks 12 to 52. Three HF patients were withdrawn because of high (n = 1) or low (n = 2) serum potassium. The most common patiromer-related adverse event was hypomagnesaemia (8.6%).

Conclusions: In patients with a clinical diagnosis of HF, diabetes, CKD, and HK on ACE-I/ARB, patiromer was well tolerated and effective for HK treatment over 52 weeks.

Trial registration: ClinicalTrials.gov NCT01371747.

Keywords: Heart failure; Hyperkalaemia; Patiromer; RAASi.

© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Figures

Figure 1

AMETHYST‐DN study design. *eGFR 15 to 2. †Primary endpoint. ‡RAASi therapy was continued after patiromer discontinuation only in patients who were normokalaemic (serum K+ ≤ 5.0 mEq/L) at the last on‐treatment visit. ACR, albumin‐to‐creatinine ratio; BID, twice daily; BP, blood pressure; CKD, chronic kidney disease; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; K+, potassium; PRN, as needed; RAASi, renin–angiotensin–aldosterone system inhibitors; spiro, spironolactone; Wk, week.

Figure 2

Least squares mean (95% CI) serum potassium levels over 52 weeks and during the follow‐up period in patients with (A) or without (B) HF. Serum potassium values [mmol/L (95% CI)] at baseline were as follows: in the HF subgroup, 5.11 (5.03, 5.20) for mild and 5.61 (5.28, 5.94) for moderate hyperkalaemia; and in the non‐HF subgroup, 5.16 (5.08, 5.23) for mild and 5.74 (5.59, 5.89) for moderate hyperkalaemia. All serum potassium analyses are based on central laboratory values. P‐values for least squares mean changes from baseline (for 52 weeks of treatment period) and from Week 52 (or time of last dose of patiromer; for follow‐up period). Least squares mean values are based on a mixed‐effects repeated‐measures model with serum potassium value as the dependent variable, time point and starting dose as fixed‐effect predictors, baseline central laboratory serum potassium value as a continuous covariate, and patient as a random effect. A compound symmetry matrix was fit. Least squares mean values for the follow‐up period are based on the same model described, while the baseline covariate used was the last potassium value before study termination. The blue shaded area denotes the target range for serum potassium (4.0–5.0 mmol/L during the treatment period and 3.8–5.0 mmol/L during the long‐term maintenance period). CI, confidence interval; HF, heart failure; HK, hyperkalaemia; K+, potassium; LS, least squares; N, number of patients at baseline and each successive 4‐week interval. *P ≤ 0.001; †P < 0.01.