Abstract Body (Do not enter title and authors here): Background: Patients with end-stage renal disease (ESRD) undergoing dialysis and with concomitant heart failure (HF) experience substantial cardiovascular risks. Although mineralocorticoid receptor antagonists (MRAs) are guideline-recommended for HF management, their utilization in dialysis-dependent populations is constrained by safety concerns and a paucity of outcome data.
Objective: This study aimed to evaluate the association of spironolactone use with the risks of major adverse cardiovascular events (MACE) and all-cause mortality among dialysis patients with HF.
Methods: This retrospective cohort study utilized data from the TriNetX US collaborative network, encompassing over 122 million patients. We identified adult patients with ESRD undergoing dialysis and diagnosed with HF between 2015 and 2024. Spironolactone users (n=6,951) were propensity score-matched (1:1) to non-users. The primary endpoints were the 5-year incidence of MACE and all-cause mortality. Cox proportional hazards regression and Kaplan-Meier survival analysis were employed. Subgroup and sensitivity analyses were performed to assess the robustness of the findings.
Results: Compared to non-users, spironolactone users exhibited significantly reduced 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). Subgroup analyses revealed consistent reductions in mortality across various patient characteristics, including sex, age, and comorbidities such as diabetes, ischemic heart disease, and atrial fibrillation (Figure 1). Kaplan-Meier survival curves illustrated a sustained benefit throughout the follow-up period . Conversely, spironolactone use was associated with increased risks of ischemic stroke (HR: 1.157), hypotension (HR: 1.197), and hyperkalemia (HR: 1.086). Baseline left ventricular ejection fraction (LVEF) did not differ significantly between the groups (p=0.802).
Conclusion: In this cohort of dialysis patients with HF, spironolactone administration was associated with lower MACE and all-cause mortality, albeit with an increased incidence of hyperkalemia and ischemic stroke. These findings advocate for the judicious use of spironolactone in this high-risk cohort, while emphasizing the imperative for randomized controlled trials (RCTs) to confirm its efficacy and safety profile.