Alpha-blockers as medical expulsive therapy for ureteral stones: a Cochrane Systematic Review

To assess the effects of alpha-blockers compared to standard therapy or placebo for ureteral stones 1 cm and less confirmed by imaging in adult patients presenting with symptoms of ureteral stone disease.

We performed a systematic search in multiple databases and grey literature with no restrictions on the language of publication or publication status, up until November 2017. We included randomised controlled trials evaluating ureteral stone passage in adult patients, that compared alpha-blockers with standard therapy or placebo. Two review authors were independently responsible for study selection, data extraction, and risk of bias assessment. We performed a meta-analysis using a random effect model. The quality of evidence was assess on outcome basis according to GRADE.

We included 67 studies, with 10,509 participants overall. Of these, 15 studies with 5787 participants used a placebo. Stone clearance: treatment with an alpha-blocker may result in a large increase in stone clearance (RR 1.45, 95% CI 1.36 to 1.55; low quality evidence). corresponding to 278 more (95%CI: 223 more to 340 more) stone clearances per 1000 participants. Major adverse events: treatment with an alpha-blocker may have little effect on major adverse events (RR 1.25, 95% CI 0.80 to 1.96; low quality evidence); this corresponds to 5 more (CI 4 fewer to 19 more) major adverse events per 1000 participants. Patients treated with alpha-blockers may also experience shorter stone expulsion times (MD -3.40 days, 95% CI: -4.17 to -2.63; low quality evidence), use less diclofenac (MD -82.41, 95% CI -122.51 to -42.31; low quality evidence) and likely require fewer hospitalizations (RR 0.51, 95% CI 0.34 to 0.77; moderate quality evidence). Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI 0.53 to 1.02; low quality evidence). Based on a predefined subgroup analysis (test for subgroup difference, p = 0.002), there may be a different effect of alpha-blockers based on stone size with RRs of 1.06 (95% CI 0.98 to 1.15; P = 0.16; I² = 62%) for stones 5 mm or less versus 1.45 (95% CI 1.22 to 1.72; P < 0.0001; I² = 59%) for stones greater than 5 mm. We did not find evidence for possible subgroup effects based on stone location or alpha-blocker type.

In patients with ureteral stones, alpha-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that alpha-blockers may be less effective in smaller (5 mm or less) than larger stones (greater than 5 mm) This article is protected by copyright. All rights reserved.

BJU international. 2018 Jun 16 [Epub ahead of print]

Thijs Campschroer, Xiaoye Zhu, Robin W M Vernooij, M T W Tycho Lock

Department of Urology, Rijnstate Hospital Arnhem, Arnhem, Netherlands., Department of Urology, University Medical Center Utrecht, Utrecht, Netherlands., Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands.