Direct effects of Tadalafil on lower urinary tract symptoms versus indirect effects mediated through erectile dysfunction symptom improvement: Integrated data analyses from 4 placebo controlled clinical studies

Gerald B. Brock, Kevin T. McVary, Claus Roehrborn, Steven Watts, Xiao Ni, Lars Viktrup, David G. Wong, Craig Donatucci

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Purpose Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction. Materials and Methods Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score). Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms. Results A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of -2.3 (p <0.0001) in total I-PSS vs -2.2 (p = 0.0007) for men without erectile dysfunction. The correlation between change from baseline in total I-PSS and IIEF-EF was weak (r2 = 0.08, p <0.0001). The unidirectional path analysis model suggested that the total treatment effect on total I-PSS score improvement (2.25) was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidirectional path analysis showed that total I-PSS improvement was largely attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement. Conclusions Regardless of the analytical approach, self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction.

Original languageEnglish (US)
Pages (from-to)405-411
Number of pages7
JournalJournal of Urology
Volume191
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • erectile dysfunction
  • phosphodiesterase 5 inhibitors
  • prostatic hyperplasia
  • tadalafil

ASJC Scopus subject areas

  • Urology

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