Cardiovascular and survival outcomes associated with spironolactone use in dialysis-dependent heart failure
B Hsiao, L W LinAbstract
Backgrounds
Patients with end-stage renal disease (ESRD) receiving maintenance dialysis and coexisting heart failure (HF) face a disproportionately high burden of cardiovascular morbidity and mortality. Although mineralocorticoid receptor antagonists (MRAs) are cornerstone therapies for HF, their use in dialysis-dependent populations remains limited owing to safety concerns and insufficient outcome evidence.
Objective
To examine the association between spironolactone therapy and the risks of major adverse cardiovascular events (MACE) and all-cause mortality in dialysis patients with HF.
Methods
Using the TriNetX U.S. collaborative network comprising more than 122 million individuals, we conducted a retrospective cohort analysis of adults diagnosed with both ESRD and HF between 2015 and 2024. Patients prescribed spironolactone (n=6,951) were propensity score–matched 1:1 with non-users based on demographic, clinical, and comorbidity profiles. The primary outcomes were 5-year incidences of MACE and all-cause mortality. Cox proportional hazards regression and Kaplan–Meier survival analyses were applied, with subgroup and sensitivity analyses to confirm robustness.
Results
Spironolactone use was associated with significantly lower risks of MACE (HR 0.892, 95% CI 0.850–0.937) and all-cause mortality (HR 0.738, 95% CI 0.694–0.786) compared with matched non-users. Mortality reductions were consistent across key subgroups defined by age, sex, and comorbidities such as diabetes, ischemic heart disease, and atrial fibrillation. Kaplan–Meier curves demonstrated a sustained survival benefit throughout follow-up. However, spironolactone users exhibited higher incidences of ischemic stroke (HR 1.157), hypotension (HR 1.197), and hyperkalemia (HR 1.086). Baseline left ventricular ejection fraction (LVEF) did not differ between groups (p=0.802).
Conclusion
In this large real-world cohort of dialysis patients with HF, spironolactone therapy was associated with improved cardiovascular and survival outcomes, counterbalanced by a modest increase in hyperkalemia and ischemic stroke risk. These findings underscore the potential role of spironolactone in the cardiorenal continuum and highlight the need for prospective randomized trials to establish its safety and efficacy in this high-risk population.Forest plot of all-cause mortalityFor image description, please refer to the figure legend and surrounding text.KM curve for all-cause mortalityFor image description, please refer to the figure legend and surrounding text.