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Novel potassium binders as enabling therapy in heart failure

Hyperkalaemia is a common problem in patients with heart failure (HF). For example, in the contemporary PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, patients with hyperkalaemia or estimated glomerular filtration rate of < 30 mL/min/1.73 m2 at screening were excluded, and those who developed hyperkalaemia during the 4–6 weeks run-in phase were also disqualified.1 Despite this, ∼1 in six patients developed serum potassium (K+) levels of > 5.5 mmol/L during the trial duration of 27 months. In PIONEER-HF (Comparison of Sacubitril/Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) trial, 10% of patients with decompensated HF developed hyperkalaemia within only 8 weeks.2 Concern for hyperkalaemia often results in failure to initiate or maximize dosing of renin–angiotensin–aldosterone system inhibitors (RAASi). Around 30% of the eligible HF patients are not prescribed mineralocorticoid receptor antagonists (MRA) because of the fear of hyperkalaemia.3,4 Furthermore, most RAASi trials have excluded patients with hyperkalaemia or advanced chronic kidney disease (CKD), leading to a major knowledge gap regarding the role of these agents in high-risk patients. This is concerning as RAASi have established benefits in HF patients who are otherwise at risk of hyperkalaemia, e.g. those with CKD or diabetes mellitus or older age. Secondary analyses of RAASi trials have demonstrated that the benefit of RAASi was independent of the risk for developing hyperkalaemia. However, with safety being a primary concern, the guidelines recommend lowering the dose or discontinuation of RAASi therapy in HF patients who develop hyperkalaemia.5 To maximize the use of RAASi and simultaneously maintaining normokalaemia, several new options have emerged. Novel potassium binders such as patiromer and sodium zirconium cyclosilicate (SZC) effectively normalize hyperkalaemia and maintain normokalaemia with acceptable safety and tolerability profile, as opposed to sodium polystyrene sulfonate.6–8 Considering that long-term options for treatment of hyperkalaemia are limited and