Patiromer-Facilitated Renin-Angiotensin-Aldosterone System Inhibitor Utilization in Patients with Heart Failure with or without Comorbid Chronic Kidney Disease: Subgroup Analysis of DIAMOND Randomized Trial

Am J Nephrol. 2024;55(6):672-689. doi: 10.1159/000540453. Epub 2024 Aug 19.

Abstract

Introduction: Renin-angiotensin-aldosterone system inhibitor (RAASi; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high.

Methods: The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK+) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m2 (added post hoc).

Results: In total, 81.3, 78.9, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer versus placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer versus placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups.

Conclusion: Patiromer enabled use of RAASi, controlled sK+, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups.

Keywords: Adverse effects; Adverse events; Chronic kidney disease; DIAMOND trial; Hyperkalemia; Mineralocorticoid receptor antagonist; Renin-angiotensin-aldosterone system inhibitors (RAASis).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / administration & dosage
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate*
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Humans
  • Hyperkalemia* / epidemiology
  • Hyperkalemia* / etiology
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists* / administration & dosage
  • Mineralocorticoid Receptor Antagonists* / adverse effects
  • Mineralocorticoid Receptor Antagonists* / therapeutic use
  • Polymers* / administration & dosage
  • Polymers* / therapeutic use
  • Potassium / blood
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Renin-Angiotensin System* / drug effects
  • Stroke Volume / drug effects

Substances

  • patiromer
  • Mineralocorticoid Receptor Antagonists
  • Polymers
  • Angiotensin-Converting Enzyme Inhibitors
  • Potassium
  • Angiotensin Receptor Antagonists

Grants and funding

The DIAMOND study was funded by Vifor Pharma Inc.