Assessment of combination therapies versus phosphodiesterase type 5 inhibitor monotherapy for erectile dysfunction: A systematic review and meta-analysis

Abstract

ABSTRACT Introduction Combining two first-line treatments for erectile dysfunction (ED) or initiating other effective modalities on top of phosphodiesterase type 5 inhibitors (PDE5i) may produce beneficial outcomes. Objective To assess the efficacy and safety of different combination therapies with PDE5i compared to PDE5i monotherapy in various subgroups of patients with ED through a systematic review and meta-analysis. Methods We considered randomized trials on males with ED that assessed the effect of combination therapy versus PDE5i monotherapy with validated questionnaires. Studies were identified by searching Medline, Cochrane Library and Scopus databases We undertook a meta-analysis for the mean international index of erectile function (IIEF) change, and for the number of adverse events (AEs) based on different treatment modalities and subgroups of patients. Results We included 3,853 individuals (44 trials). Combination therapy with PDE5i, compared to PDE5i monotherapy, was associated with a mean IIEF improvement of 1.92 points (95% CI: 1.41 to 2.44, I2=82%). Adding to PDE5i: daily tadalafil, low-intensity shockwave therapy, vacuum erectile device or antioxidants resulted in a significant IIEF improvement. The latter was not observed with a-blockers. Compared to monotherapy, combination treatment improved IIEF in patients with hypogonadism, monotherapy-resistant or prostatectomy-induced ED. The treatment-related AEs did not differ between combination treatment with PDE5i and PDE5i monotherapy (OR:1.10, 95% CI: 0.66 to 1.85, I2=78%). Still, despite multiple subgroup and sensitivity analyses, the levels of heterogeneity for all outcomes remained high. Conclusions Combination therapy with PDE5i and antioxidants improves ED without increasing the AEs, while treatment with PDE5i and daily tadalafil, shockwaves or vacuum device seems effective, but data are scarce. Combination treatment should be initially preferred in patients with hypogonadism or prostatectomy-induced ED. Conversely, the addition of a-blockers to PDE5i does not provide additional efficacy in patients with urinary symptoms. Overall, combination therapy with PDE5i is safe and effective and should be considered as first-line treatment for refractory or difficult-to-treat cases of ED. Disclosure Work supported by industry: no.