Elsevier

European Urology Focus

Volume 3, Issue 1, February 2017, Pages 27-45
European Urology Focus

Review – Stone Disease
Medical Expulsive Therapy in Urolithiasis: A Review of the Quality of the Current Evidence

https://doi.org/10.1016/j.euf.2017.05.002Get rights and content

Abstract

Context

Medical expulsive therapy (MET) is widely used to promote spontaneous passage of urinary stones. However, there is conflicting evidence on the actual role of MET.

Objective

To evaluate the conformance of published randomized controlled trials (RCTs) on MET with the Consolidated Standards for Reporting Trials (CONSORT) criteria, and to clarify the current role of MET in management of urinary stones on the basis of our findings.

Evidence acquisition

We carried out an electronic search of the Cochrane Library, PubMed, and Embase databases for RCTs on MET. For each RCT included, we created a checklist table documenting the minimum essential items that should be included in reports of RCTs according to the CONSORT 2010 statement.

Evidence synthesis

Clinical heterogeneity between pooled studies in terms of the MET given, inclusion criteria, sample size, pre- and post-treatment imaging, and differential follow-up was profound. The overall methodological rigor of the pooled studies was low, as indicated by the moderate to poor conformance of the studies with the CONSORT criteria. The aforementioned reasons may explain the discrepancies found between the supporting results of several meta-analyses and those of well-designed placebo-controlled double-blind studies revealing no benefit from MET. Recent well-designed RCTs have shown no benefit from α-blockers versus placebo. However, on the basis of sensitivity analyses in a recently published meta-analysis, α-blockers may still promote spontaneous expulsion of large stones.

Conclusions

Conflicting data on MET may be explained by clinical heterogeneity and methodological flaws. Urologists must decide whether to follow single, large, well-conducted RCTs or pooled data from meta-analyses. The latter still support selective use of MET for larger urinary stones.

Patient summary

In this review we tested the accuracy of the studies published on various medications given to promote spontaneous passage of stones from the ureter. Although the majority of the studies were not designed properly, there is still some evidence to support medical expulsive therapy.

Introduction

The prevalence of urinary stone disease is high among the general population, with a significant risk of recurrence. Acute presentation and treatment of urolithiasis may significantly affect the health-related quality of life of patients [1]. Medical expulsive therapy (MET) is aimed at promoting spontaneous passage of ureteral stones and reducing the stone expulsion time after lithotripsy. Pharmaceutical agents such as calcium channel blockers, corticosteroids, nonsteroidal anti-inflammatory drugs, terpene compound products, plant extracts, and α-blockers have been investigated as methods to enhance spontaneous stone passage [2]. The most widely studied agents are α-blockers. The rationale for using α-blockers is to decrease both the frequency and amplitude of ureteral peristalsis above the stone and reduce ureteral spasm at the stone location [3]. These changes are accompanied by an increase in the intraureteral urine flow and the stone expulsion rate as the intraureteral pressure decreases [4]. Several meta-analyses support the clinical use of MET for ureteral stone management either without previous treatment [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17] or after shock wave lithotripsy [18], [19], [20], [21]. In general, these studies showed that α-blockers and calcium channel blockers lead to better expulsion rates compared to controls, with quicker stone passage and reductions in pain episodes and analgesic requirements. α-Blockers seem to be more effective compared to calcium channel blockers [13] and the relatively newly released α-blocker silodocin may be better compared to the widely used tamsulosin [14], [15]. However, the latest meta-analysis suggested that the stone passage rate was independent of the choice of drug [17]. Previous systematic reviews and meta-analyses included all the published randomized controlled trials (RCTs) regardless of their quality, and the authors acknowledged the weaknesses of many of the studies and called for better large RCTs to confirm the effect. Recently, large, well-designed, double-blind, placebo-controlled trials showed no significant effect of MET on spontaneous stone passage [22], [23], [24], [25]. The contradictory results from meta-analyses of small RCTs compared to large multicenter trials demonstrate the vulnerability of meta-analyses. In order to evaluate the strength of RCTs of MET, we set out to identify variance among the different studies on the basis of their compliance with the Consolidated Standards for Reporting Trials (CONSORT) criteria for properly designed randomized studies [26].

Section snippets

Evidence acquisition

We carried out an electronic search of the Cochrane Library, PubMed, and Embase databases. The keywords we used were as follows: urinary stone; urolithiasis; ureteral colic; lithotripsy; kidney stone; ureteral stone; spontaneous stone passage; medical therapy; medical expulsive therapy; and randomized controlled study. Peer-reviewed papers written in English for which the full text was accessible were the only search limitations. Reference lists in the original manuscripts for the studies

Evidence synthesis

Our search revealed 86 RCTs [4], [22], [23], [24], [25], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]

Conclusions

The variety in the design of various RCTs as shown by the differences in conformance with the CONSORT criteria may explain the discrepancies found between well-designed RCTs and meta-analyses, as well as between different meta-analyses. Pooled results for all studies after performing sensitivity analyses still suggest that α-blockers may facilitate the passage of larger ureteric stones, regardless of their location. Given the low risk profile of these drugs, urologists may still consider MET in

References (117)

  • F. Porpiglia et al.

    Effectiveness of nifedipine and deflazacort in the management of distal ureter stones

    Urology

    (2000)
  • J.T. Cooper et al.

    Intensive medical management of ureteral calculi

    Urology

    (2000)
  • F. Porpiglia et al.

    Role of adjunctive medical therapy with nifedipine and deflazacort after extracorporeal shock wave lithotripsy of ureteral stones

    Urology

    (2002)
  • F. Porpiglia et al.

    Nifedipine versus tamsulosin for the management of lower ureteral stones

    J Urol

    (2004)
  • B. Kupeli et al.

    Does tamsulosin enhance lower ureteral stone clearance with or without shock wave lithotripsy?

    Urology

    (2004)
  • E. Yilmaz et al.

    The comparison and efficacy of 3 different α1-adrenergic blockers for distal ureteral stones

    J Urol

    (2005)
  • S. Resim et al.

    Role of tamsulosin in treatment of patients with steinstrasse developing after extracorporeal shock wave lithotripsy

    Urology

    (2005)
  • G.L. Gravina et al.

    Tamsulosin treatment increases clinical success rate of single extracorporeal shock wave lithotripsy of renal stones

    Urology

    (2005)
  • M. Dellabella et al.

    Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi

    J Urol

    (2005)
  • M. Dellabella et al.

    Medical-expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life

    Urology

    (2005)
  • S. Micali et al.

    Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study

    J Urol

    (2006)
  • S. Erturhan et al.

    Comparative evaluation of efficacy of use of tamsulosin and/or tolterodine for medical treatment of distal ureteral stones

    Urology

    (2007)
  • S.K. Bhagat et al.

    Is there a role for tamsulosin in shock wave lithotripsy for renal and ureteral calculi?

    J Urol

    (2007)
  • V. Naja et al.

    Tamsulosin facilitates earlier clearance of stone fragments and reduces pain after shockwave lithotripsy for renal calculi: results from an open-label randomized study

    Urology

    (2008)
  • R.N. Pedro et al.

    Alfuzosin stone expulsion therapy for distal ureteral calculi: a double-blind, placebo controlled study

    J Urol

    (2008)
  • X. Sun et al.

    Efficacy of selective α1D-blocker naftopidil as medical expulsive therapy for distal ureteral stones

    J Urol

    (2009)
  • T. Hermanns et al.

    Is there a role for tamsulosin in the treatment of distal ureteral stones of 7 mm or less? Results of a randomised, double-blind, placebo-controlled trial

    Eur Urol

    (2009)
  • M.M. Agarwal et al.

    Is there an adjunctive role of tamsulosin to extracorporeal shockwave lithotripsy for upper ureteric stones: results of an open label randomized nonplacebo controlled study

    Urology

    (2009)
  • M. Agrawal et al.

    Prospective randomized trial comparing efficacy of alfuzosin and tamsulosin in management of lower ureteral stones

    Urology

    (2009)
  • O. Aydogdu et al.

    Effectiveness of doxazosin in treatment of distal ureteral stones in children

    J Urol

    (2009)
  • H. Wang et al.

    Effect of alpha1-adrenergic antagonists on lower ureteral stones with extracorporeal shock wave lithotripsy

    Asian J Surg

    (2010)
  • A.A. Zehri et al.

    Preliminary study of efficacy of doxazosin as a medical expulsive therapy of distal ureteric stones in a randomized clinical trial

    Urology

    (2010)
  • A. Al-Ansari et al.

    Efficacy of tamsulosin in the management of lower ureteral stones: a randomized double-blind placebo-controlled study of 100 patients

    Urology

    (2010)
  • F.C. Vicentini et al.

    Adjuvant tamsulosin or nifedipine after extracorporeal shock wave lithotripsy for renal stones: a double blind, randomized, placebo-controlled trial

    Urology

    (2011)
  • M.I. Georgiev et al.

    Efficacy of tamsulosin oral controlled absorption system after extracorporeal shock wave lithotripsy to treat urolithiasis

    Urology

    (2011)
  • I. Mokhless et al.

    Tamsulosin for the management of distal ureteral stones in children: a prospective randomized study

    J Pediatr Urol

    (2012)
  • A.K. Ibrahim et al.

    Efficacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones

    Arab J Urol

    (2013)
  • H.R. Gandhi et al.

    The efficacy of tamsulosin vs. nifedipine for the medical expulsive therapy of distal ureteric stones: a randomised clinical trial

    Arab J Urol

    (2013)
  • S. Erturhan et al.

    Efficacy of medical expulsive treatment with doxazosin in pediatric patients

    Urology

    (2013)
  • S. Kumar et al.

    Role of tamsulosin, tadalafil, and silodosin as the medical expulsive therapy in lower ureteric stone: a randomized trial (a pilot study)

    Urology

    (2015)
  • A. Raja et al.

    How do urinary calculi influence health-related quality of life and patient treatment preference: a systematic review

    J Endourol

    (2016)
  • S.J. Sowter et al.

    The management of ureteric colic

    Curr Opin Urol

    (2006)
  • S.C. Picozzi et al.

    Management of ureteral calculi and medical expulsive therapy in emergency departments

    J Emerg Trauma Shock

    (2011)
  • Z. Lu et al.

    Tamsulosin for ureteral stones: a systematic review and meta-analysis of a randomized controlled trial

    Urol Int

    (2012)
  • M.E. Chua et al.

    Terpene compound drug as medical expulsive therapy for ureterolithiasis: a meta-analysis

    Urolithiasis

    (2013)
  • B. Fan et al.

    Can tamsulosin facilitate expulsion of ureteral stones? A meta-analysis of randomized controlled trials

    Int J Urol

    (2013)
  • T. Campschroer et al.

    Alpha-blockers as medical expulsive therapy for ureteral stones

    Cochrane Database Syst Rev

    (2014)
  • H. Wang et al.

    Comparative efficacy of tamsulosin versus nifedipine for distal ureteral calculi: a meta-analysis

    Drug Des Dev Ther

    (2016)
  • M. Ozsoy et al.

    Comparison of silodosin to tamsulosin for medical expulsive treatment of ureteral stones: a systematic review and meta-analysis

    Urolithiasis

    (2016)
  • H. Ding et al.

    The role of silodosin as a new medical expulsive therapy for ureteral stones: a meta-analysis

    Renal Failure

    (2016)
  • View full text