Is tadalafil associated with decreased risk of major adverse cardiac events or venous thromboembolism in men with lower urinary tract symptoms?

PURPOSE: To evaluate the association of tadalafil, a phosphodiesterase-5 inhibitor (PDE5I), with major adverse cardiac events (MACE) or venous thromboembolism (VTE) in men with lower urinary tract symptoms (LUTS). METHODS: Data was obtained from the TriNetX Research Network, ICD-10 codes were used to identify men with LUTS, MACE, and VTE. In addition, demographic characteristics and use of tadalafil or alpha-blocker was evaluated. Then, unbalanced and balanced association analyses was performed to assess the relation between tadalafil and/or alpha-blocker use with MACE/VTE. RESULTS: After participant selection, analysis included 821,592 men that did not use an alpha blocker or tadalafil, 5,004 men that used tadalafil but no alpha blocker, 327,482 men that used an alpha blocker but no tadalafil, and 6,603 men that used both an alpha blocker and tadalafil. On balanced analysis, tadalafil was independently associated with a decreased risk of MACE/VTE within a 3-year time period (OR = 0.59, 95%CI 0.49–0.70, p < 0.0001). Among men with a history of alpha blocker use, tadalafil use was also independently associated with a decreased risk of MACE or VTE, both before and after controlling for potentially confounding variables (OR = 0.57, 95%CI: 0.50–0.66; p < 0.0001). CONCLUSIONS: In our study, tadalafil was associated with a decreased risk of MACE/VTE in men with LUTS with and without a history of alpha blocker use. It is time to perform further long-term prospective randomized studies to further analyze the cardiovascular effects of PDE5Is as combination treatment with alpha blockers in the management of LUTS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00345-022-04005-3.