Abstract
Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic.Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews.Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups.Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: −0.8, 95% CI: −1.65-0.06).Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile.Systematic Review Registration: PROSPERO, identifier [CRD42020216754].
Highlights
Phosphodiesterase type 5 (PDE5) inhibitors are considered the first-line treatment in patients with erectile dysfunction (ED) due to their safety and efficacy profile (Salonia et al, 2021)
20 were meta-analyses or network meta-analyses that included a total of 258 relevant meta-analytic effects (Shabsigh et al, 2007; Vecchio et al, 2010; Xiao et al, 2012; Taylor et al, 2013; Yuan et al, 2013; Schmidt et al, 2014; Chen et al, 2015; García-Perdomo et al, 2017; Tan et al, 2017; Tian et al, 2017; D’Andrea et al, 2019; Lai et al, 2019; Li et al, 2019; Liao et al, 2019; Liu et al, 2019; Zhou et al, 2019; Adamou et al, 2020; Madeira et al, 2020; Wang et al, 2020; Zhu et al, 2020; Mykoniatis et al, 2021)
The mean overall AMSTAR 2 score of 11 ± 2.9 indicated that the methodological quality of most of the included systematic reviews was generally of sufficient standard (Supplementary Data S4)
Summary
Phosphodiesterase type 5 (PDE5) inhibitors are considered the first-line treatment in patients with erectile dysfunction (ED) due to their safety and efficacy profile (Salonia et al, 2021). Due to the increasing interest in PDE5 inhibitors, available systematic reviews and meta-analyses have explored the effect of PDE5 inhibitors on multiple outcomes (Greenberg et al, 2019). Physicians and policymakers require, in most cases, a holistic approach of a given topic to facilitate their evidence-based clinical decision-making (Allen and Walter, 2019). In this scope, overviews of systematic reviews and meta-analyses or umbrella reviews are a promising, new approach that assimilates the vast amount of available research and contextualizes the magnitude of a specific topic (Hunt et al, 2018). Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. Physicians and policymakers require a holistic approach of this topic
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