Can We Stop Reflexively Discontinuing Mineralocorticoid Antagonists for Patients With Heart Failure and Hyperkalemia?

Abstract

The importance of promptly introducing low doses of multiple classes of guideline-directed medical therapy (GDMT) in patients with symptomatic heart failure is underscored in the recent heart failure guidelines. 1 Heidenreich PA Bozkurt B Aguilar D et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Card Fail. 2022; 28: e1-e167https://doi.org/10.1016/j.cardfail.2022.02.010 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Concerns purported to foster the underuse of GDMT include inadequate patient and laboratory follow-up, patient nonadherence, medication-related expenses, polypharmacy, and the perceived risk of hyperkalemia (Fig. 1). 2 Greene SJ Butler J Albert NM et al. Medical therapy for heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018; 72: 351-366https://doi.org/10.1016/j.jacc.2018.04.070 Crossref PubMed Scopus (412) Google Scholar Such trepidations commonly lead to avoidance or premature discontinuation of mineralocorticoid antagonists (MRAs). Observational data show that a single episode of hyperkalemia is cited as justification for cessation of MRAs in approximately 30% of patients; severe hyperkalemia (K+ ≥ 6 mmol/L) occurs in only one-quarter of those patients, but is commonly labeled as medication intolerance. 3 Trevisan M Fu EL Xu Y et al. Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care. Eur J Heart Fail. 2021; 23: 1698-1707https://doi.org/10.1002/ejhf.2287 Crossref PubMed Scopus (10) Google Scholar MRA discontinuation decreases the incidence of recurrent hyperkalemia but confers a 10%–30% increased downstream risk of mortality and cardiovascular events. 3 Trevisan M Fu EL Xu Y et al. Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care. Eur J Heart Fail. 2021; 23: 1698-1707https://doi.org/10.1002/ejhf.2287 Crossref PubMed Scopus (10) Google Scholar ,4 Siddiqi Tariq J Usman Muhammad S Abid M et al. Is stopping mineralocorticoid receptor antagonists after hyperkalemia associated with increased mortality in heart failure? A systematic review and meta-analysis. J Am Coll Cardiol. 2022; 79: 406https://doi.org/10.1016/S0735-1097(22)01397-3 Crossref Google Scholar Thus, patients are frequently deprived of life-saving therapies owing to hyperkalemia concerns. In this article, we present evidence supporting MRA continuation in the setting of mild hyperkalemia, suggest mitigation strategies and interventions for moderate to severe hyperkalemia, and expand on new and future options that may help attenuate the overall risk of hyperkalemia and its complications.