Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial

Javed Butler*, Stefan D. Anker*, Lars H. Lund, Andrew J.S. Coats, Gerasimos Filippatos, Tariq Jamal Siddiqi, Tim Friede, Vincent Fabien, Mikhail Kosiborod, Marco Metra, Ileana L. Piña, Fausto Pinto, Patrick Rossignol, Peter van der Meer, Cecilia Bahit, Jan Belohlavek, Michael Böhm, Jasper J. Brugts, John G.F. Cleland, Justin EzekowitzAntoni Bayes-Genis, Israel Gotsman, Assen Goudev, Irakli Khintibidze, Joann Lindenfeld, Robert J. Mentz, Bela Merkely, Eliodoro Castro Montes, Wilfried Mullens, Jose C. Nicolau, Aleksandr Parkhomenko, Piotr Ponikowski, Petar M. Seferovic, Michele Senni, Evgeny Shlyakhto, Alain Cohen-Solal, Peter Szecsödy, Klaus Jensen, Fabio Dorigotti, Matthew R. Weir, Bertram Pitt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

AIMS: To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13-43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: -0.10 mmol/l (95% confidence interval, CI -0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. CONCLUSION: Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066).

Original languageEnglish
Pages (from-to)4362-4373
Number of pages12
JournalEuropean Heart Journal
Volume43
Issue number41
DOIs
Publication statusPublished - 1 Nov 2022

Bibliographical note

Funding Information:
This work was supported by Vifor Pharma. Funding to pay the Open Access publication charge for this article was provided by Vifor Pharma.

Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of European Society of Cardiology.

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