ED Medications in Kidney Failure: PDE5 Inhibitors Linked to Lower Mortality and Heart Risk in ESRD

[madman]

Abstract​

INTRODUCTION AND OBJECTIVES:​

Erectile dysfunction (ED) affects over 70% of men with end-stage renal disease (ESRD), yet the cardiovascular safety of phosphodiesterase type 5 inhibitors (PDE5i) in this population remains poorly understood. Concerns persist due to altered pharmacokinetics and hemodynamic effects in renal failure, leading to underutilization of these agents. We aimed to evaluate the safety of ED medications in men with ESRD using TriNetX, a large, multicenter electronic health record network.

METHODS:​

We conducted a retrospective cohort study on July 1, 2025, using the TriNetX U. S. Collaborative Network, comprising over 117 million patients across 70 healthcare organizations. Adult males diagnosed with ESRD (N18.6) and ED (N52) were identified. Cohort 1 included patients prescribed ED medications (ATC G04BE) within one month of ED diagnosis; Cohort 2 included those not prescribed ED medications following ED diagnosis. Patients with renal transplantation were excluded. One-to-one propensity score matching was performed on age, race, ethnicity, and comorbidities. The primary outcomes were 1-year and 5-year incidence of cardiovascular, neurological, thrombotic, and mortality outcomes. Risk ratios (RR) and hazard ratios (HR) were calculated using standardized TriNetX analytics, with significance defined as p<0.05.

RESULTS:​

After matching, each cohort included 4,248 patients with balanced demographics, comorbidities, and follow up time. At 1 year, ED medication users had lower incidence of ischemic heart disease (RR 0.81, 95%, p = 0.04) and arrhythmia (RR 0.82, 95%, p = 0.02). Mortality was significantly reduced in the medicated group (RR 0.70, 95%, p<0.001). At 5 years, mortality remained lower but was not statistically significant (RR 0.93, 95%, p = 0.09). No increased risk was observed for cerebrovascular events, hypotension, or thrombotic complications across all timepoints.

CONCLUSIONS:​

In this large, real-world cohort of men with ESRD and ED, use of ED medications was associated with lower 1-year mortality and reduced risk of cardiovascular and arrhythmic events, without evidence of increased risk of neurologic or hemodynamic complications. These findings support the cardiovascular safety of PDE5i in ESRD and suggest possible cardioprotective effects warranting further prospective investigation.