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Efficacy of PDE-5-inhibitors for erectile dysfunction. A comparative meta-analysis of fixed-dose regimen randomized controlled trials administering the International Index of Erectile Function in broad-spectrum populations

Abstract

This meta-analytic study aims to estimate the likely improvements of erectile dysfunction (ED) measured by the International Index of Erectile Function (IIEF) at the highest fixed dosages of the three available PDE-5-inhibitors: sildenafil, tadalafil, and vardenafil. MEDLINE and the Cochrane Library were searched electronically for efficacy trials of PDE-5-inhibitors for treating ED. In addition drug manufacturers were contacted to provide unpublished or unrecorded congress proceedings. Randomized, double-blind, placebo-controlled, parallel-group, maximum fixed-dose, broad-spectrum efficacy trials using IIEF were included in the analysis. Data were independently extracted by two reviewers. The results were pooled using weighted mean differences. A formal indirect comparison (including Bonferroni-correction) was conducted to estimate the differences between agents. A total of 14 trials were included in the meta-analysis (three with 100 mg sildenafil, eight with 20–25 mg tadalafil, and three with 20 mg vardenafil). All trials were of good methodological quality. Overall heterogeneity was moderate: I2=33.2%, χ2=19.47, P=0.11. The funnel plot suggested moderate likelihood of publication bias. Pooled results of IIEF-improvement were for sildenafil 9.65 (95% CI: 8.50, 10.79) points, tadalafil 8.52 (7.61, 9.42) points, and vardenafil 7.50 (6.50, 8.50) points, respectively. Sildenafil proved to be significantly more effective than vardenafil (d=2.15, P=0.006), other pairwise comparisons showed no difference in efficacy. All PDE-5-inhibitors are highly effective in the treatment of ED. At maximum dosage they improve erectile function 7–10 points on the IIEF compared to placebo-treatment. There is evidence that sildenafil might be more efficacious than vardenafil, although this is to be interpreted with caution. To prove higher efficacy truly independent comparative trials are needed.

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Correspondence to M M Berner.

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Conflict of interest

There was no specific funding for this project. MB currently holds research grants from the German Ministry for Education and Research, Boehringer Ingelheim Inc., Pfizer Inc. and Willmar Schwabe Inc. He did receive tuition fees from Glaxo Smith Kline, Hormosan Kwizda, Lilly, Pfizer and Willmar Schwabe. He also received travel expenses from the European Sexual Dysfunction Alliance affiliate (ISG e.V.) that receives sponsoring from the pharmaceutical industry. LK did receive travel expenses reimbursement from Pfizer and Wilmar Schwabe. AH holds a paid part time position with the European Sexual Dysfunction Alliance affiliate (ISG e.V.).

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Berner, M., Kriston, L. & Harms, A. Efficacy of PDE-5-inhibitors for erectile dysfunction. A comparative meta-analysis of fixed-dose regimen randomized controlled trials administering the International Index of Erectile Function in broad-spectrum populations. Int J Impot Res 18, 229–235 (2006). https://doi.org/10.1038/sj.ijir.3901395

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Keywords

  • impotence
  • phosphodiesterase inhibitors
  • meta-analysis
  • treatment outcome
  • randomized controlled trials

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