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

Abstract

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.

Comment on: “Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study”

“…Without the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire for grading in the evaluation of ED severity, along with other ED assessments, e.g., Sexual Health Inventory for Men (SHIM), Erection Hardness Scale (EHS), penile doppler ultrasound and endothelial function [10], stratification was impossible to judge the decision of ULT discontinuation. Tadalafil might be preferred over other PDEIs partially because of its longer half-life (17.5 h) and because it was associated with a decreased risk of major adverse cardiac events or venous thromboembolism [11]. Retrieval of relevant information could help to identify the proportion of severe subjects on medication.…”

The increasing role of PDE5Is in men with diabetes and cardiovascular disease

“…PDE5Is are first‐line agents in treatment for erectile dysfunction, and importantly, longitudinal studies suggest that PDE5Is reduce all‐cause mortality in men with T2DM, previous myocardial infarction, erectile dysfunction (Figure 1) and benign prostatic hypertrophy (BPH). A review of PDE5Is and all‐cause mortality (excluding pulmonary hypertension and heart failure) identified five recent studies 8,9–12 . These studies show a significant reduction in all‐cause mortality and morbidity associated with PDE5I use in men with T2DM, the general population and men with lower urinary tract symptoms (LUTS).…”

“…In the second study, Goberdhan et al . investigated 851 492 men with BPH treated with alpha blocker versus daily tadalafil and reported a 43% reduction in MACE/thrombotic events over three years with daily tadalafil 9 …”

“…A review of PDE5Is and all-cause mortality (excluding pulmonary hypertension and heart failure) identified five recent studies. 8,[9][10][11][12] These studies show a significant reduction in all-cause mortality and morbidity associated with PDE5I use in men with T2DM, the general population and men with lower urinary tract symptoms (LUTS).…”