Management of RAASi-associated hyperkalemia in patients with cardiovascular disease

Abstract

Renin-angiotensin-aldosterone system inhibitors (RAASi) reduce morbidity and mortality in heart failure (HF) with reduced ejection fraction in a dose-dependent manner. They also have a positive impact in other cardiovascular diseases (CVDs). However, RAASi may induce hyperkalemia, a potentially life-threatening disorder. This risk is further increased in those with concomitant chronic kidney disease, diabetes mellitus, and/or in patients with hypertension. Current treatment guidelines recommend maximal RAASi dosing to improve clinical outcomes; however, this is often limited by the development of hyperkalemia. When this occurs, current guidelines recommend RAASi down-titration/interruption, which, while improving short-term prognosis, is associated with a negative long-term prognostic impact. At present, the European Society of Cardiology suggests the consideration of novel potassium binders (patiromer and sodium zirconium cyclosilicate) for the management of RAASi-associated hyperkalemia. Both drugs can reduce serum potassium levels and prevent recurrent hyperkalemia. Additionally, patiromer showed enabling of RAASi optimization in high-risk patients. Nevertheless, precise recommendations on the use of these drugs are lacking. Building upon current HF guideline recommendations, a multidisciplinary expert panel convened to design an algorithm providing practical guidance on the use of novel potassium binders/patiromer in patients with HF and/or other CVD. As a result of that effort, we present an evidence-based treatment algorithm for the management of hyperkalemia with novel potassium binders/patiromer in patients with HF and/or other CVD receiving RAASi, including the necessary monitoring to avoid induction of hypokalemia. This algorithm aims to maintain or up-titrate RAASi to optimized doses, while maintaining normokalemia, improved clinical outcomes, and long-term prognosis.

Keywords: Heart failure with reduced ejection fraction; Hyperkalemia; Novel potassium binders; RAASi optimization; Renin–angiotensin–aldosterone system inhibitors.

Fig. 1

Treatment algorithm for the management of RAASi-associated hyperkalemia in patients with heart failure and/or other cardiovascular diseases ^aCKD 3b–4 = eGFR > 15–45 mL/min/1.73 m². ^bPatiromer should be administered at least 3 h apart from other oral medications to reduce the possibility of drug–drug interactions. CKD chronic kidney disease, DM diabetes mellitus, eGFR estimated glomerular filtration rate, HF heart failure, K⁺ potassium, Mg magnesium, RAASi renin–angiotensin–aldosterone system inhibitor