Managing hyperkalemia in patients with heart failure on guideline-directed medical therapy: challenges and opportunities

Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium-glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure. Despite remarkable improvements in the morbidity and mortality of heart failure, however, many patients still develop clinically significant hyperkalemia during combined treatment with those four pharmacological pillars. The consequence is often a down-titration or discontinuation of one or more crucial drugs, which in turns leads to a considerable increase in the risk of cardiovascular events, dialysis, and all-cause mortality. This paper will explore novel approaches for the management of hyperkalemia in heart failure, including closer monitoring of potassium levels, early review of drugs that might increase the risk of hyperkalemia, and pharmacological treatment of hyperkalemia, with a special emphasis on sodium-glucose-cotransporter 2 inhibitors and potassium-binding agents, including patiromer and sodium zirconium cyclosilicate.