Hyperkalaemia as a cause of undertreatment with mineralocorticoid receptor antagonists in heart failure

To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up-titration of guideline-directed medical therapy (GDMT) in real-world settings.

A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up-titration.

Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up-titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P < 0.0001), had lower EF (P = 0.022), had higher NTproBNP (P = 0.017), had lower eGFR (P = 0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P < 0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6 months of up-titration of GDMT (P < 0.0001). Among four groups, the incidence of hyperkalaemia throughout up-titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P < 0.0001). In the MRA-naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6 months of up-titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively.

Hyperkalaemia increased significantly during up-titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.