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

Abstract

Aims 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. Methods 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. Results 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. Conclusions 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.

Real-world effectiveness of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a retrospective, non-interventional cohort analysis

“…In the EMPHASIS-HF Trial hyperkalemia (≥5.5 mmol/L) was present in 11.8% of eplerenone-treated groups [3] . In our daily clinical practice, we found a significant increase in hyperkalemia from 5.9% at baseline to 24.4% after 6 months of up-titration of GDMT in hig-risk patient groups: older patients (≥65 years), patients with multiple comorbidities, and patients with lower GFR levels [8] .…”

“…However, their clinical implementation remains suboptimal. In Sweden, approximately half of patients with HFrEF do not receive MRA treatment, and among those treated, most receive only half of the target dose [5][6][7][8] . Likewise, globally usage often falls below target dosage [9][10] .…”

Enhancing implementation of evidence-based heart failure therapies in clinical practice: vital to modern medicine

“…In both inpatient and outpatient settings, the optimization of treatment appears slow, irregular, unequal, and incomplete. Shockingly, the utilization of GDMT in routine clinical practice remains remarkably low, with discontinuation rate of mineralocorticoid receptor antagonists (MRA) reaching as high as 42% [4][5] . In the Heart Failure Drug Treatment-Inertia, Titration, and Discontinuation: A Multinational Observational Study (EVOLUTION HF), encompassing patients initiating any GDMT within 12 months of post-hospitalization for HF, the initiation of novel GDMT is often delayed, with few patients receiving target doses necessitating uptitration among the 266,589 patients [6] .…”