Introduction: The pharmacological armamentarium for treating lower urinary tract symptoms (LUTS) includes multiple drug classes: alpha-blockers, 5a-reductase inhibitors, and phosphodiesterase type 5 inhibitors (PDE5I). Alpha-blockers are associated with cardiac failure and 5a-reductase inhibitors can be associated with long-term sexual dysfunction. PDE5i causes vasodilation, which may provide some cardiovascular protection. We aim to evaluate if men receiving PDE5Is (Tadalafil) for LUTS will have a decreased risk of major adverse cardiac events (MACE) or venous thromboembolism (VTE).
Methods: Data was obtained from the TriNetX Research Network, ICD-10 codes were used to identify LUTS, MACE, and VTE, additionally, demographic characteristics, prescriptions for tadalafil and a-blocker, and confounding variables (age, race/ethnicity, history of hyperlipidemia, diabetes mellitus, hypertension, obesity, heart disease, stroke, sleep apnea, use of nicotine, ß-blockers, ACE inhibitors, aspirin, clopidogrel, antilipemic agates, and finasteride/dutasteride) were evaluated. Analysis was performed to assess the association between tadalafil and/or alpha-blocker use with MACE/VTE.
Results: A total of 1,160,681 men were identified, of them 821,592 did not use an a-blocker or tadalafil, 5,004 used tadalafil but no a-blocker, 327,482 used an a-blocker but no tadalafil, and 6,603 that used both an a-blocker and tadalafil. On balanced analysis, tadalafil was associated with a decreased risk of MACE/VTE within a three-year period (OR = 0.59; p<0.0001). Among men with a history of a-blocker use, tadalafil use was also associated with a decreased risk of MACE/VTE, both before and after controlling for potentially confounding variables.
Conclusions: Tadalafil was associated with decreased risk of MACE/VTE in men with LUTS with and without a history of alpha-blockers use in a large population database. Tadalafil for the treatment of LUTS might provide a cardiovascular benefit due to its beneficial effects on vasodilation and endothelial function. Prospective trials using PDE5i in treatment of men with LUTS should evaluate cardiovascular benefit in addition to improvement in LUTS.
Source of Funding: This work was supported in part by National Institutes of Health Grant R01 DK130991 to Ranjith Ramasamy