Letter regarding the article ‘ Effects of hyperkalaemia and non‐adherence to renin–angiotensin–aldosterone system inhibitor therapy in patients with heart failure in Italy : a propensity‐matched study’

We read with great interest the paper by Volterrani et al.1 In this observational cohort of heart failure (HF) patients on renin–angiotensin–aldosterone system inhibitors (RAASi), patients with hyperkalaemia had an increased risk of cardiovascular events or death. Furthermore, among the patients with hyperkalaemia, 77% were not adherent to RAASi therapy in the 12 months after the index date (the first date of hospitalization discharge related to HF), and these patients had an increased risk of mortality. We agree with the authors' main conclusion that further investigation is required for achieving optimal treatment of RAASi in hyperkalaemic conditions. A limitation of the study was that Volterrani et al. only assessed non-adherence to RAASi in an outpatient setting, but not in acute decompensation. Namely, there were patients who had discontinued RAASi due to hyperkalaemia before discharge after HF-related hospitalization. We would like to add several comments to this point. The decision on whether to withdraw from HF medications in the hospital-based setting is at the discretion of the treating physician and may be driven by multiple factors, including potassium levels.2 Despite the importance of this process during the management of hospitalized HF patients, data surrounding in-hospital management are scarce compared to that of medical management in a stable outpatient setting.3-5 In our registry-based data-set that included 4000 consecutive hospitalized HF patients (West-Tokyo Heart Failure Registry) between 2006 and 2015, 683 patients with systolic HF, without advanced renal disease (ejection fraction <50% and estimated glomerular filtration rate ≥30 min/mL/1.73 m2), were treated with RAASi on admission. The patients were predominantly male (68.4%) with a median age of 74 years (interquartile range: 63, 82 years), and their median serum potassium levels on admission were 4.3 mEq/L (interquartile range: 4.0, 4.7 mEq/L). On admission, 9.2% (n = 63) of patients had hyperkalaemia (K >5.0 mEq/L). The proportions of patients who discontinued RAASi at discharge were 19.0% among patients with hyperkalaemia on admission and 11.6% among those without (Figure 1A). These results suggest that hyperkalaemia on admission could be a trigger for non-adherence to RAASi at discharge with acute HF. Meanwhile, among patients with hyperkalaemia on admission, over 80% did not have hyperkalaemia at discharge irrespective of whether RAASi was continued at discharge (RAASi continuation, 91.0%; and RAASi discontinuation, 83.3%) (Figure 1B). Therefore, it is plausible that non-adherence to RAASi at discharge in hospitalized HF patients may be an overreaction, predisposing patients to additional risk. There is potential room for improvement in the optimization of RAASi therapy [e.g. RAASi continuation, enabled by strict monitoring of potassium level (plus use of potassium binders)]. We appreciate the authors' efforts on this research and also would like to propose that further investigation be performed to attain optimal treatment with RAASi, while minimizing hyperkalaemia-associated risk not only in chronic settings, but also in hospital-based settings.