Hyperkalemia, guideline-directed medical therapy and outcomes in heart failure patients followed at a tertiary center

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AIM: To assess the impact of hyperkalemia on the optimization of heart failure therapy and clinical outcomes in a specialized tertiary care center. METHODS: We retrospectively analyzed data from 690 heart failure patients, categorized into hyperkalemia and no-hyperkalemia groups based on the occurrence of serum potassium greater than 5 mEq/l at any time during follow-up. Baseline characteristics and long-term therapy patterns were compared. Predictors of hyperkalemia were evaluated through logistic regression analysis. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models. Four sensitivity analyses were performed, considering moderate hyperkalemia (K ≥ 5.5 mEq/l), propensity score-matched cohorts, heart failure with reduced ejection fraction (HFrEF), and HFrEF population after the approval of sacubitril/valsartan in Italy. RESULTS: Hyperkalemia occurred in 16% of patients and was associated with chronic kidney disease and lower ejection fraction. Baseline use of renin-angiotensin-aldosterone system inhibitors (RAASi), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) was similar between groups, with consistent prescription patterns during follow-up. Approximately 75% of patients in both groups maintained stable RAASi therapy, defined as continuous treatment throughout follow-up. Survival curves showed no significant difference between hyperkalemia and no-hyperkalemia patients. However, those maintaining or initiating RAASi therapy had significantly better long-term survival, regardless of hyperkalemia status. Hyperkalemia was not an independent predictor of mortality [hazard ratio 1.04, 95% confidence interval (CI) 0.72-1.52, P = 0.83], while consistent RAASi use was strongly protective (hazard ratio 0.48, 95% CI 0.33-0.71, P < 0.001). Similar results were observed for secondary endpoints, as well as across all sensitivity analyses. CONCLUSION: In a structured heart failure outpatient setting, hyperkalemia is not an insurmountable barrier to maintaining guideline-directed therapy. Continued RAASi use confers significant prognostic benefit, highlighting the importance of specialized follow-up.

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