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

Butler, J. et al. (2022) Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial. European Heart Journal, 43(41), pp. 4362-4373. (doi: 10.1093/eurheartj/ehac401) (PMID:35900838) (PMCID:PMC9622299)

Abstract

Aims: To investigate the impact of patiromer on 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 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 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 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 adjusted mean change between patiromer and placebo: -0.10 [95% confidence interval, CI -0.13, -0.07] mmol/L, 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).

• Item Type: Articles
• Additional Information: Funding: Vifor Pharma.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Butler, J., Anker, S. D., Lund, L. H., Coats, A. J.S., Filippatos, G., Siddiqi, T. J., Friede, T., Fabien, V., Kosiborod, M., Metra, M., Piña, I. L., Pinto, F., Rossignol, P., van der Meer, P., Bahit, C., Belohlavek, J., Böhm, M., Brugts, J. J., Cleland, J. G.F., Ezekowitz, J., Bayes-Genis, A., Gotsman, I., Goudev, A., Khintibidze, I., Lindenfeld, J., Mentz, R. J., Merkely, B., Montes, E. C., Mullens, W., Nicolau, J. C., Parkhomenko, A., Ponikowski, P., Seferovic, P. M., Senni, M., Shlyakhto, E., Cohen-Solal, A., Szecsödy, P., Jensen, K., Dorigotti, F., Weir, M. R., and Pitt, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: European Heart Journal
• Publisher: Oxford University Press
• ISSN: 0195-668X
• ISSN (Online): 1522-9645
• Published Online: 28 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in European Heart Journal 43(41): 4362-4373
• Publisher Policy: Reproduced under a Creative Commons License