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 Three HF patients were withdrawn because of high (n = 1) or low (n = 2) serum potassium.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.

• Authors: Bertram Pitt, George L Bakris, Matthew R Weir, Mason W Freeman, Mitja Lainscak, Martha R Mayo, Dahlia Garza, Rezi Zawadzki, Lance Berman, David A Bushinsky
• Journal: ESC heart failure (ESC Heart Fail) Vol. 5 Issue 4 Pg. 592-602 (08 2018) ISSN: 2055-5822 [Electronic] England
• PMID: 29767459 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Biomarkers
• Spironolactone
• Losartan
• Potassium

Topics

• Angiotensin II Type 1 Receptor Blockers (administration & dosage)
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage)
• Biomarkers (blood)
• Diabetic Nephropathies (blood, complications)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Follow-Up Studies
• Heart Failure (blood, complications, physiopathology)
• Hyperkalemia (blood, drug therapy, etiology)
• Losartan (administration & dosage)
• Potassium (blood)
• Retrospective Studies
• Spironolactone (administration & dosage)
• Stroke Volume (physiology)
• Time Factors
• Treatment Outcome