Association of daily and on-demand tadalafil use with all-cause mortality and cardiovascular outcomes in men with erectile dysfunction and lower urinary tract symptoms: a propensity score-matched real-world cohort study
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Background Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia are common conditions in middle-aged and older men and are associated with an increased risk of cardiovascular disease and mortality. Emerging evidence suggests that phosphodiesterase type 5 (PDE5) inhibitors may provide cardiovascular benefits beyond symptomatic improvement. Tadalafil is unique among PDE5 inhibitors because it is prescribed as either a once-daily low-dose regimen (5 mg) or an on-demand high-dose regimen (20 mg). However, whether these dosing strategies differ in their association with long-term mortality and cardiovascular outcomes remains uncertain. This study evaluated the association of daily tadalafil 5 mg and on-demand tadalafil 20 mg use with all-cause mortality and cardiovascular outcomes in men with ED and/or LUTS. Methods This retrospective cohort study used de-identified electronic health record data from the TriNetX US Collaborative Network. Men aged ≥ 40 years diagnosed with ED and/or LUTS between January 2012 and December 2022 who received tadalafil 5 mg or tadalafil 20 mg were identified and compared with patients who did not receive PDE5 inhibitors. Patients with pre-existing major cardiovascular disease, exposure to other PDE5 inhibitors, or receipt of both tadalafil regimens were excluded. A two-phase analysis was performed, comparing each tadalafil regimen with non-users, followed by a direct comparison between tadalafil 5 mg and tadalafil 20 mg. Propensity score matching was performed for demographic characteristics and major comorbidities. The primary outcomes were all-cause mortality, cerebrovascular accident, heart failure, and ischaemic heart disease in the period of 14 years of follow-up. Results The final study population included 28,376 patients receiving tadalafil 5 mg, 31,321 receiving tadalafil 20 mg, and 1,066,587 patients who did not receive PDE5 inhibitors. After propensity score matching, both tadalafil 5 mg and tadalafil 20 mg were associated with significantly lower risks of all-cause mortality (risk ratio [RR] 0.574 and 0.617, respectively), cerebrovascular accident (RR 0.727 and 0.818), heart failure (RR 0.668 and 0.704), and ischaemic heart disease (RR 0.819 and 0.856) compared with non-users. In the propensity score-matched head-to-head comparison, Kaplan–Meier analyses demonstrated improved overall survival (HR 1.116, 95% CI 1.033–1.205; P = 0.005) and cardiovascular disease-free survival (HR 1.050, 95% CI 1.010–1.091; P = 0.013) among patients receiving tadalafil 20 mg compared with tadalafil 5 mg. Conclusions Among men aged ≥ 40 years with ED and/or LUTS, treatment with either tadalafil 5 mg or tadalafil 20 mg was associated with lower risks of all-cause mortality and individual cardiovascular outcomes compared with non-use of PDE5 inhibitors. In this observational study, on-demand tadalafil 20 mg was associated with more favourable long-term survival outcomes than daily tadalafil 5 mg in time-to-event analyses. Prospective randomized studies are warranted to confirm these findings and determine whether the observed associations reflect a causal treatment effect. (Clinical trial number: not applicable)
Source: Research Square
Institution: Taichung Veterans General Hospital
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7222892253