Head-to-head Comparison of the Safety and Efficacy Profiles of Three Phosphodiesterase Type 5 Inhibitors through Patient-reported Outcomes of 130 000 Patients from a Direct-to-consumer Platform Database

Eur Urol Focus. 2025 Nov 18:S2405-4569(25)00308-6. doi: 10.1016/j.euf.2025.11.006. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Direct-to-consumer (DTC) telemedical platforms facilitate the discreet management of sensitive medical conditions, including erectile dysfunction. We aimed to use a large dataset to generate a head-to-head comparison on the efficacy, onset of action, and adverse events (AEs) of phosphodiesterase type 5 inhibitors (PDE5is).

METHODS: Data for this retrospective cohort study were obtained from a data pool of 132 100 patients treated with sildenafil, tadalafil, or vardenafil. Efficacy, onset of action, and AEs collected by digital questionnaires were used as the primary endpoints. Group comparisons between intermediate/high and low doses of the respective PDE5is were performed for AEs (sildenafil, tadalafil, and vardenafil) and efficacy as well as onset of action (sildenafil vs tadalafil).

KEY FINDINGS AND LIMITATIONS: Medium (50 mg) and high (100 mg) doses of sildenafil improved patient satisfaction (mean change in score ± standard deviation [SD] 2.534 ± 1.3 vs 2.235 ± 1.4, p < 0.0001) and sexual performance (mean change in score ± SD for hardness: 2.245 ± 1.2 vs 2.105 ± 1.3, p < 0.0001, and for maintenance: 2.264 ± 1.2 vs 2.120 ± 1.3, p < 0.0001), compared with similar doses of tadalafil (10 and 20 mg). Sildenafil (35.0%, 3572/10 201) and tadalafil (33.9%, 2225/6564) revealed similar AE rates (d = 0.011, 95% confidence interval [CI]: -0.0037 to 0.0257, p = 0.1424), but vardenafil revealed higher rates (47.4%, 268/565) than sildenafil (d = -0.124, 95% CI: -0.166 to -0.082, p < 0.0001). Nasal congestion was the most common AE across all PDE5is concerning medium/high doses. Sildenafil was less likely to cause reflux compared with tadalafil (5.3%, 536/10 201 vs 8.0%, 523/6564; d = -0.027, 95% CI: -0.035 to -0.019, p < 0.0001). Conversely, tadalafil was less associated with flushing (7.3%, 438/10 201 vs 152/6564; d = 0.02, 95% CI: 0.014-0.025, p < 0.001). Limitations include a relatively healthy patient population.

CONCLUSIONS AND CLINICAL IMPLICATIONS: PDE5i usage is associated with distinct efficacy and AE profiles in a large real-world dataset guiding treatment recommendations for urologists. Future DTC data might be used to complement clinical trial data.

PMID:41261009 | DOI:10.1016/j.euf.2025.11.006