Efficacy And Safety Of Pde5-Is And Alpha-1 Blockers For Treating Distal Ureteral Calculi: A Mixed Treatment Comparison Network Meta-Analysis Of Randomized Controlled Clinical Trials

Background and aims: Ureteral calculi are frequent diseases in urology. Medical expulsive therapy is one of the standard treatments, but the efficacy is still controversial. The goal of this study was to investigate the efficacy and safety of monotherapy or combination therapy with alpha-blockers and phosphodiesterase 5 inhibitors for in the treatment of distal ureteral calculi. Methods: Randomized controlled trials as of July 2018 were searched from PubMed, Cochrane Library, Web of Science, and Embase to compare the above drug categories for patients with distal ureteral calculi using appropriate search strategies. An inverse variance model was used for the comparison of mixed treatments. The calculi expulsion rate (SER) is the primary and the calculi expulsion time (SET) is the primary-secondary outcome measure. Results: This network meta-analysis included 11 trials involving 1509 participants, which indicated that tamsulosin (RR: 2.46; 95% CI, 1.05-6.21), tadalafil (RR: 4.08; 95% CI, 1.78-9.98), silodosin (RR: 7.28; 95% CI, 2.48-21.87), tadalafil combined with tamsulosin (RR: 6.33; 95% CI, 1.83-20.18), and tadalafil combined with silodosin (RR: 20.25; 95% CI, 3.93-97.23) has a significant higher calculi expulsion rate compared with placebo, and network comparisons indicated that tadalafil (RR: 1.64; 95%01, 1.07-2.65), silodosin (RR: 2.75; 95% CI, 1.44-5.65), tadalafil combined with tamsulosin (RR: 2.45; 95% CI, 1.05-5.45), and tadalafil combined with silodosin (RR: 7.47; 95% CI, 1.72-32.92) has a significantly higher calculi expulsion rate compared with tamsulosin. At the same time, this network meta-analysis shows that tadalafil combined with silodosin is significantly shorter than other treatments in terms of calculi expulsion time. A comparison of the side effects of tamsulosin and tadalafil showed that the tadalafil group had higher headache, dizziness, backache, and orthostatic hypotension than the tamsulosin group. Further, there was no evidence of statistical heterogeneity between studies (P > 0.05). It is interesting that tadalafil significantly improved ejaculation abnormalities in male patients compared with tamsulosin (P < 0.05). Conclusion: In conclusion, alpha-blockers, PDE5-Is, PDE5-Is combined with alpha-blockers significantly increased the expulsion rate of distal ureteral calculi. Among these interventions, tadalafil combined with silodosin is likely to be "best". At the same time, tadalafil combined with silodosin may further shorten the expulsion time of distal ureteral calculi.