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