The Comparative Effectiveness of PDE5 Inhibitors and β3 Agonists Versus α-Blockers in Medical Expulsive Therapy for Distal Ureteric Stones: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Urolithiasis is a common urinary tract disease. This systematic review and meta-analysis aim to evaluate the effectiveness of alpha-blockers compared to novel therapies. The objective of this systematic review and meta-analysis was to compare the efficacy and safety of emerging pharmacologic therapies, namely tadalafil and mirabegron, with traditional alpha-blockers, such as tamsulosin and silodosin, as medical expulsive therapies (METs) for distal ureteric stones measuring ≤10 or <5 mm. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines were implemented during the conduct of this systematic review. A systematic review and meta-analysis of randomized controlled trials was conducted involving adult patients with distal ureteric stones. A total of six studies have been included, and quality assessment has been performed individually. Subgroup analyses were made using forest plots and funnel plots to study the odds ratios (ORs), confidence intervals (CIs), and heterogeneity of the articles. The studies included patients treated with various agents (tamsulosin, silodosin, tadalafil, and mirabegron) for up to four weeks. The primary outcome was the expulsion rate of the stones. Secondary outcomes included stone expulsion time (SET), analgesic use, hospital visits, and adverse effects. For the stone expulsion rate (SER), in the mirabegron subgroup, an overall pooled OR of 0.98 (95% CI: 0.26-3.66) with high heterogeneity was obtained (I² = 79%, p = 0.02), indicating substantial variability among the included studies. This could be due to the limited number of studies that require further investigation through a sensitivity analysis. In the tadalafil subgroup, an overall pooled OR of 1.79 (95% CI: 0.62-5.14) was obtained with tadalafil showing a better trend toward outcomes compared to alpha-blockers, but the result was not statistically significant. For the secondary outcomes, the tadalafil subgroup showed a significant reduction in the SET compared to alpha-blockers, with a pooled mean difference (MD) of -2.08 days (95% CI: -3.14 to -1.02), indicating no heterogeneity. However, the mirabegron subgroup obtained a pooled MD of 0.16 days (95% CI: -6.06 to 6.38) with very high heterogeneity (I² = 97%, p < 0.0001), suggesting large variability between the studies and no statistically significant difference in expulsion time between mirabegron and alpha-blockers. For the amount of analgesia used, an overall MD of 4.54 mg (95% CI: -53.19 to 62.27) was obtained, indicating no statistically significant difference in analgesic use between the newer drugs and alpha-blockers (p = 0.88). The frequency of adverse effects was noted more in the alpha-blocker group, with significant ejaculation and orthostatic hypertension noted in silodosin only, and insignificant side effects in both the mirabegron and tadalafil groups. It is concluded from this study that tadalafil is clinically better than alpha-blockers in the MET of distal ureteric stones of <10 mm. Tadalafil has a higher SER and a lower expulsion time, and requires a reduced amount of analgesia. However, given that pooled results are not statistically significant, the following require further evaluation. On the contrary, alpha-blockers are still better than mirabegron, but again, this is not statistically significant enough to prove their supremacy.