Patiromer for Heart Failure Medication Optimization in Patients With Current or Past Hyperkalemia: DIAMOND Subanalysis

Andrew J S Coats; Stefan D Anker; Lars H Lund; Gerasimos Filippatos; Patrick Rossignol; Bertram Pitt; Matthew R Weir; Mikhail N Kosiborod; Marco Metra; Michael Böhm; Justin A Ezekowitz; Antoni Bayes-Genis; Robert J Mentz; Piotr Ponikowski; Michele Senni; John G F Cleland; Assen Goudev; Irakli Khintibidze; Joann Lindenfeld; Bela Merkely; Sandra Waechter; Jeffrey Budden; Amandine Perrin; Javed Butler

doi:10.1016/j.jchf.2024.08.003

Patiromer for Heart Failure Medication Optimization in Patients With Current or Past Hyperkalemia: DIAMOND Subanalysis

JACC Heart Fail. 2024 Sep 12:S2213-1779(24)00602-4. doi: 10.1016/j.jchf.2024.08.003. Online ahead of print.

Authors

Andrew J S Coats¹, Stefan D Anker², Lars H Lund³, Gerasimos Filippatos⁴, Patrick Rossignol⁵, Bertram Pitt⁶, Matthew R Weir⁷, Mikhail N Kosiborod⁸, Marco Metra⁹, Michael Böhm¹⁰, Justin A Ezekowitz¹¹, Antoni Bayes-Genis¹², Robert J Mentz¹³, Piotr Ponikowski¹⁴, Michele Senni¹⁵, John G F Cleland¹⁶, Assen Goudev¹⁷, Irakli Khintibidze¹⁸, Joann Lindenfeld¹⁹, Bela Merkely²⁰, Sandra Waechter²¹, Jeffrey Budden²², Amandine Perrin²¹, Javed Butler²³

Affiliations

¹ Heart Research Institute, Sydney, New South Wales, Australia. Electronic address: ajscoats@aol.com.
² Department of Cardiology (CVK) of German Heart Center Charité, Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany; Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.
³ Department of Medicine, Unit of Cardiology, Karolinska Institutet, Solna, Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
⁴ National and Kapodistrian University of Athens, School of Medicine, Athens University Hospital Attikon, Athens, Greece.
⁵ Université de Lorraine, Centre d'Investigations Cliniques-Plurithématique 14-33, Inserm U1116, CHRU Nancy, and F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France; Medical Specialties and Nephrology Departments, Princess Grace Hospital, and Monaco Private Hemodialysis Centre, Monaco, Monaco.
⁶ Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁸ Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri, USA.
⁹ Cardiology, ASST Spedali Civili and University, Brescia, Italy.
¹⁰ Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany.
¹¹ Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
¹² Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, CIBERCV, Spain.
¹³ Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁴ Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.
¹⁵ University of Milano-Bicocca, Cardiovascular Department, Papa Giovanni XXIII Hospital, Bergamo, Italy.
¹⁶ Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom.
¹⁷ Department of Emergency Medicine, Medical University of Sofia, Sofia, Bulgaria.
¹⁸ Alexandre Aladashvili Clinic, Tbilisi State Medical University, Tbilisi, Georgia.
¹⁹ Department of Medicine, Vanderbilt University Medical Centre, Nashville, Tennessee, USA.
²⁰ Semmelweis University Heart and Vascular Center, Budapest, Hungary.
²¹ CSL Vifor, Glattbrugg, Switzerland.
²² CSL Vifor, Redwood City, California, USA.
²³ Department of Medicine, University of Mississippi, Jackson, Mississippi, USA.

PMID: 39340493
DOI: 10.1016/j.jchf.2024.08.003

Abstract

Background: For heart failure with reduced ejection fraction (HFrEF), suboptimal use of renin-angiotensin-aldosterone system inhibitors (RAASis), including mineralocorticoid receptor antagonists (MRAs), due to hyperkalemia, may be improved by potassium binders.

Objectives: This prespecified analysis of the phase 3 DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial assessed the effect of patiromer in patients with HFrEF and either current or past hyperkalemia.

Methods: Patients with HFrEF and current or past (within 1 year before enrollment) hyperkalemia (serum potassium [sK⁺] >5.0 mmol/L) entered a single-blind, run-in phase to optimize RAASis while receiving patiromer. They were subsequently randomized, double-blind, to continue patiromer or change to placebo.

Results: Of the 1,038 patients who completed run-in, 354 (83.9%) of 422 with current hyperkalemia and 524 (85.1%) of 616 with past hyperkalemia achieved RAASi optimization and were randomized to treatment. During the double-blind phase, patiromer lowered sK⁺ levels compared with placebo in both the current and past hyperkalemia subgroups: difference in adjusted mean change from baseline: -0.12 (95% CI: -0.17 to -0.07) and -0.08 (95% CI: -0.12 to -0.05), respectively; P_interaction = 0.166. Patiromer was more effective than placebo in maintaining MRA at target dose in patients with current vs past hyperkalemia (HR: 0.45 [95% CI: 0.26-0.76] vs HR: 0.85 [95% CI: 0.54-1.32]; P_interaction = 0.031). Adverse events were similar between subgroups.

Conclusions: The use of patiromer facilitates achieving target doses of RAASis in patients with HFrEF with either current or past hyperkalemia. For those with current hyperkalemia before RAASi optimization, use of patiromer may be more beneficial in helping to maintain sK⁺ control and achieve MRA target dose. (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure [DIAMOND]; NCT03888066).

Keywords: heart failure with reduced ejection fraction; hyperkalemia; patiromer; potassium binder; renin-angiotensin-aldosterone system inhibitor.

Associated data

ClinicalTrials.gov/NCT03888066