Systematic review and meta-analysis of the adjuvant role of Medical Expulsive Therapy (MET) in Shock Wave Lithotripsy (SWL) treatment of upper urinary stones

Nikolaos Grivas, Panagiotis Kallidonis, Panagiotis Mourmouris, Thomas Rountos, Alexandros Fiamegos, Sotirios Stavrou, Chris Venetis, Andreas Skolarikos, The Members of RISTA Study Group The Members of RISTA Study Group


Introduction: Medical expulsion therapy (MET) has been introduced
as a method enhancing the spontaneous passage of
stones and reducing the stone expulsion time after extracorporeal
shockwave lithotripsy (SWL). The aim of the current
meta-analysis was to analyze the data of randomized studies on
MET implemented following SWL for renal and ureteral stones.
Materials and Methods: A systematic literature search of CENTRAL,
WEB OF SCIENCE, PUBMED and SCOPUS was performed.
The criteria applied for the selection of the included studies
were: randomized, placebo or other comparator (i.e analgesics)
controlled studies dealing with renal or ureteral stones treated
with SWL and MET (including plant extracts) with a minimum follow-up of 14 days. Subgroup analyses were a priori planned
to be performed depending on the: type of α-blocker (i.e tamsulosin,
alfuzosin, terazosin, doxazosin, Urapidil), size and location
of stones. All results were combined for meta-analysis with the
Review Manager.
Results: Pooled results demonstrated the efficacy of α-blockers,
nifedipine, Rowatinex and Uriston in increasing stone clearance.
In addition, the time to stone elimination, the intensity of pain,
the formation of steinstrasse and the need for auxillary procedures
were reduced mainly with α-blockers. Expulsion rate was
not correlated with the type of α-blocker, the stone diameter
and the stone location.
Conclusions: Evidence suggests that MET can be suggested as
an adjuvant treatment after SWL due to its expulsive efficacy,
pain reduction and safety profile. However, due to the clinical
heterogeneity among the included studies, conclusions drawn


ESWL; pharmaceutical adjuvants; renal calculi; ureteral calculi

Full Text:



Türk C, Petřík A, Sarica K, et al. EAU Guidelines on Interventional

Treatment for Urolithiasis. Eur Urol. 2016;69:475-82

Preminger GM, Tiselius HG, Assimos DG, et al. American Urological

Association Education and Research, Inc; European Association of

Urology. 2007 Guideline for the management of ureteral calculi.

Eur Urol. 2007;52:1610-1631.

Skolarikos A. Management of residual stone fragments. In: Smith

AD, Badlani GH, Preminger GM, Kavoussi LR, eds. Smith’s Textbook

of Endourology 3rd ed. Blackwell Publishing Ltd; 2012:662-674

Poulakis V, Dahm P, Witzsch U, et al. Prediction of lower pole stone

clearance after shock wave lithotripsy using an artificial neural

network. J Urol. 2003;169:1250–1256.

Hedges LV, Olkin I. Statistical methods for meta-analysis. New York,

NY: Academic Press; 1985.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin

Trials. 1986;7:177-188.

Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in

meta-analyses. BMJ. 2003;327:557-560.

Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis

detected by a simple, graphical test. BMJ. 1997;315:629-634.

Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method

of testing and adjusting for publication bias in meta-analysis. Biometrics.


Ateş F, Eryıldırım B, Öztürk MI, et al. Does the use of doxazosin

influence the success of SWL in the treatment of upper ureteral

stones? A multicenter, prospective and randomized study. Urol Res.


Choi NY, Ahn SH, Han JH, et al. The effect of tamsulosin and nifedipine

on expulsion of ureteral stones after extracorporeal shock wave

lithotripsy. Korean J Urol. 2008;49:150-154.

Han MC, Jeong WS, Shim BS. Additive expulsion effect of tamsulosin

after shock wave lithotripsy for upper ureteral stones. Korean J Urol


Hirasawa Y, Ide H, Ito Y, et al. Improvement of expulsion of upper

ureteral stones by adjuvant use of Urapidil after Extracorporeal Shock

Wave Lithotripsy - a prospective randomized placebo controlled study.

J Urol Suppl. 2012;187:E908-E909.

Hussein MM. Does tamsulosin increase stone clearance after shockwave

lithotripsy of renal stones? A prospective, randomized controlled

study. Scand J Urol Nephrol. 2010;44:27-31.

Kupeli B, Irkilata L, Gurocak S, et al. Does tamsulosin enhance lower

ureteral stone clearance with or without shock wave lithotripsy?

Urology. 2004;64:1111-1115.

Wang CJ, Huang SW, Chang CH. Adjunctive medical therapy with

an alpha-1A-specific blocker after shock wave lithotripsy of lower

ureteral stones. Urol Int. 2009;82:166-169.

Wang H, Liu K, Ji Z, et al. Effect of a1-Adrenergic Antagonists on Lower

Ureteral Stones With Extracorporeal Shock Wave Lithotripsy. Asian J

Surg. 2010;33:37–41

Bhagat SK, Chacko NK, Kekre NS, et al. Is there a role for tamsulosin

in shock wave lithotripsy for renal and ureteral calculi? J Urol.


Gravas S, Tzortzis V, Karatzas A, et al. The use of tamsulosin as adjunctive

treatment after ESWL in patients with distal ureteral stone:

do we really need it? Results from a randomised study. Urol Res.


Kobayashi M, Naya Y, KinoM. Low dose tamsulosin for stone expulsion

after extracorporeal shock wave lithotripsy: efficacy in Japanese male

patients with ureteral stone. Int J Urol. 2008;15:495–498.

Mukhtarov S, Turdiev A, Fozilov A, et al. Using doxazosin for distal

ureteral stone clearance with or without shock wave lithotripsy. Eur

Urol Suppl. 2007;6:216.

Agarwal MM, Naja V, Singh SK, 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;74:989-992.

Singh SK, Pawar DS, Griwan MS, et al. Role of tamsulosin in clearance

of upper ureteral calculi after extracorporeal shock wave lithotripsy:

a randomized controlled trial. Urol J. 2011;8:14-20.

Singh SK, Pawar DS, Griwan MS. Tamsulosin as an Expulsive Therapy for

Lower Ureteric Calculus after Extra Corporeal Shock Wave Lithotripsy:

A Randomized Controlled Study. Int J Nephrol Urol. 2011;3:62-68.

Vicentini FC, Mazzucchi E, Brito AH, et al. Adjuvant Tamsulosin or

Nifedipine After Extracorporeal Shock Wave Lithotripsy for Renal

Stones: a Double Blind, Randomized, Placebo-controlled Trial. Urology.


Naja V, Agarwal MM, Mandal AK, 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;72:1006–1011.

Falahatkar S, Khosropanah I, Vajary AD, et al. Is there a role for tamsulosin

after shock wave lithotripsy in the treatment of renal and

ureteral calculi? J Endourol. 2011;25:495-498.

Baloch H, Khalid SE. Efficacy of Alfuzosin (alpha blocker) after extra

corporeal shockwave lithotripsy for passage of renal calculi Eur Urol

Suppl. 2011;10:475–500.

Shaaban Alaa M, Barsoum Nady M, Sagheer Gamal A, et al. Is there a

role for alpha blocker after SWL for renal and upper ureteral stones?

J Urol. 2008;179:A1459.

Zaytoun OM, Yakoubi R, Zahran AR, et al. Tamsulosin and doxazosin as

adjunctive therapy following shock-wave lithotripsy of renal calculi:

randomized controlled trial. Urol Res. 2012;40:327-332.

Porpiglia F, Destefanis P, Fiori C, et al. Role of adjunctive medical

therapy with nifedipine and deflazacort after extracorporeal shock

wave lithotripsy of ureteral stones. Urology. 2002;59:835–838.

Romics I, Siller G, Kohnen R, et al. A special terpene combination (Rowatinex

®) improves stone clearance after extracorporeal shockwave

lithotripsy in urolithiasis patients: results of a placebo-controlled

randomised controlled trial. Urol Int. 2011;86:102-9. Urol J. 2009;6:9-

Djaladat H, Mahouri K, Khalifeh Shooshtary F, et al. Effect of Rowatinex

on calculus clearance after extracorporeal shock wave lithotripsy. Urol

J. 2009;6:9-13.

Takada M, Yano H, Kanbara N, et al. Effect of Chorei-to on spontaneous

discharge of urinary stones after extracorporeal shock wave lithotripsy

(ESWL). Acta Urol Jpn. 1997;43:311-314.

Micali S, Sighinolfi MC, Celia A, 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;176:1020-

Sowter S, Tolley D. The management of ureteric colic. Curr Opin Urol.


Dellabella M, Milanese G, Muzzonigro G. Efficacy of tamsulosin in

the medical management of juxtavesical ureteral stones. J Urol.2003;170:2202–2205.

Kubacz GJ, Catchpole BN. The role of adrenergic blockade in the

treatment of ureteral colic. J Urol. 1972;107:949-951.

Hollingsworth JM, Rogers MAM, Kaufman SR, et al. Medical therapy

to facilitate urinary stone passage: a meta-analysis. Lancet.


Porpiglia F, Vaccino D, Billia M, et al. Corticosteroids and tamsulosin in

the medical expulsive therapy for symptomatic distal ureter stones:

single drug or association? Eur Urol. 2006;50:339-344.

Dellabella M, Milanese G, Muzzonigro G. Randomized trial of the

efficacy of tamsulosin, nifedipine and phloroglucinol in medicalexpulsive

therapy for distal ureteral calculi. J Urol. 2005;174:167-172.

Hasegawa M, Toda T, Hara N, et al. Effect of the terpene combination

in experimental calcium oxalate nephrolithiasis. Nishi Nihon Hinyo.


Koide T, Yamaguchi S, Utsunomiya M, et al. The inhibitory effect of

kampou extracts on in vitro calcium oxalate crystallization and in

vivo stone formation in an animal model. Int J Urol. 1995;2:81–86.

Madaan S, Joyce AD. Limitations of extracorporeal shock wave lithotripsy.

Curr Opin Urol. 2007;17:109–113.

Kim TH, Oh SY, Moon YT. The effect of tamsulosin on expulsion of

ureteral stones after extracorporeal shock wave lithotripsy. Korean

J Urol. 2008;49:1100–1104.

Soyupak S, Armagan A, Kosar A, et al. Risk factors for the formation of

a steinstrasse after shock wave lithotripsy. Urol Int. 2005;74:323–325.

Mahmood M, Hamid A, Tandon A, et al. The steinstrasse: A legacy of

extracorporeal lithotripsy. Ind J Urol. 2003;20:46-49.