Hyperkalemia-related Heart Failure Therapy Discontinuation and the Association with Outcomes in Patients with Heart Failure

Background Renin-angiotensin-aldosterone system (RAAS) inhibitors are essential treatments for heart failure (HF) patients, but their use is often limited by hyperkalemia. Objective This study assesses the incidence of hyperkalemia in chronic HF patients on RAAS inhibitors, examines changes in therapy following hyperkalemia episodes, and evaluates the impact of RAAS inhibitor discontinuation or down-titration on patient outcomes. Methods We conducted a population-based cohort study of patients hospitalized or visiting the emergency department in Alberta for chronic HF from April 2012 to March 2020, focusing on those with RAAS inhibitor-associated hyperkalemia. Episodes of hyperkalemia (K >5.0 mmol/L) were monitored, and patients were followed for 30 days to determine if their RAAS therapy was maintained, reduced, or discontinued. Results Among 7527 HF patients, we identified 123,038 RAAS inhibitor treatment years, resulting in 17 hyperkalemia events per 100 treatment years. Hyperkalemia led to RAAS inhibitor discontinuation in 35.2% of cases, down-titration in 8.4%, and continuation in 56.4%. Discontinuation or down-titration was more common when serum potassium exceeded 6.0 mmol/L (49.4%) compared to lower levels. Over a median follow-up of 1.4 years, discontinuing or down-titrating RAAS inhibitors was associated with increased all-cause mortality (aHR 1.80), higher cardiovascular hospitalizations (aHR 1.09), and more frequent ED visits for HF (aHR 1.17) compared to continued therapy. Conclusions Discontinuation or down-titration of RAAS inhibitors in HF patients is associated with higher mortality and cardiovascular events. Strategies to maintain RAAS therapy after hyperkalemia episodes may improve patient outcomes.