Endourology and Stones

Efficacy of Tamsulosin Oral Controlled

Absorption System After Extracorporeal
Shock Wave Lithotripsy to Treat Urolithiasis
Marin I. Georgiev, Dimitar I. Ormanov, Vasil D. Vassilev, Plamen D. Dimitrov,
Vladislav D. Mladenov, Elenko P. Popov, Petar P. Simeonov, and Petar K. Panchev
OBJECTIVE To determine the efficacy of the tamsulosin oral controlled absorption system as an adjuvant therapy
to extracorporeal shock wave lithotripsy (ESWL) for the expulsion of ureteral and renal stones.
METHODS A consecutive sample of 248 patients with ureteral or renal stones who underwent ESWL in an
academic hospital was included in a 12-week, prospective, open-label, randomized clinical trial.
Of the 248 patients, 186, including 77 with ureteral stones (mean size 9 mm) and 109 with renal
stones (mean size 13 mm) completed the study. After successful ESWL, the patients were
randomized to standard medical care (corticosteroids and analgesics) or standard care plus the
tamsulosin oral controlled absorption system 0.4 mg/d for 1 month. The stone clearance rate,
interval to the elimination of stone fragments, incidence of renal colic, and the need for
rehospitalization were assessed at 4, 8, and 12 weeks.
RESULTS The stone clearance rate was significantly greater for the patients treated with tamsulosin than
for those in the standard care group at 4 (73.4% vs 55.9%, respectively; P ⬍ .001) and 12 (91.3%
vs 74.6%, respectively; P ⬍ .05) weeks. Tamsulosin treatment was also associated with a
significantly lower interval to the elimination of stone fragments (P ⬍ .001), a significantly lower
rehospitalization rate (P ⬍ .001), and a significantly lower proportion of patients with acute renal
colic (P ⬍ .05) than standard care alone. No severe adverse events leading to treatment
discontinuation were observed.
CONCLUSION Adjuvant treatment with tamsulosin, in addition to standard treatment with steroids and analgesics,
improved the outcome of ESWL. UROLOGY 78: 1023–1028, 2011. © 2011 Published by Elsevier Inc.

Evidence that medical treatment with an ␣1-adreno-

I
n Europe and North America, an estimated 5%-10%
of the population develop urinary tract stones at least
once in their life, and about one half develop recur-
rent disease.1 Thus, stone disease is 1 of the most com-
mon problems in urologic practice.
A stone ⱕ5 mm in diameter has a 68% chance of
passing spontaneously compared with only 47% of the
stones ⬎5 and ⱕ10 mm.2 When active removal is nec-
essary, extracorporeal shock wave lithotripsy (ESWL) is
the first choice of treatment for most patients, with a
reported clearance rate for kidney stones of 66%-99% in
patients with stones ⬍20 mm3. However, the success rate
of ESWL depends on a number of factors, including the
location and composition of the stone, the lithotripter
used, and the body mass index of the patient.3
Funding Support: Astellas Pharma International funded independent medical
writing support but had no role in the design or conduct of the study, analyzing
the data, or in the preparation or approval of the manuscript.
From the Department of Urology, University Hospital “Alexandrovska,” Medical
University Sofia, Sofia, Bulgaria
Reprint requests: Marin I. Georgiev, M.D., Department of Urology, University
Hospital “Alexandrovska,” Medical University Sofia, 1 G. Sofiiski Street, Sofia 1431
Bulgaria. E-mail: marinbg64@gmail.com
Submitted: October 12, 2010, accepted (with revisions): January 21, 2011
ceptor (AR) antagonist or a calcium antagonist could
improve the clearance of stone fragments generated with
ESWL is growing.4 Thus, medical expulsive therapy ad-
juvant to ESWL could potentially decrease they costs
related to repeat ESWL or other treatment options such
as retrograde ureteroscopic lithotripsy or percutaneous
nephrolithotomy. In addition, this treatment approach
fits with current clinical practice, characterized by more
and more patients requesting a conservative and/or min-
imally invasive therapeutic approach.
Because of this first evidence, we designed a prospec-
tive clinical study in Bulgaria. The aim of the present
randomized trial was to evaluate the efficacy and safety of
the ␣1-AR antagonist tamsulosin oral controlled absorp-
tion system as adjuvant therapy to ESWL for expulsion of
renal and ureteral stones.
MATERIAL AND METHODS
Inclusion Criteria
Patients aged 18-80 years with ureterolithiasis along the entire
length of the ureter or nephrolithiasis (excluding lower pole
calices) were included in the present prospective randomized

© 2011 Published by Elsevier Inc. 0090-4295/11/$36.00 1023

doi:10.1016/j.urology.2011.01.073
clinical trial if the stone size was 5-20 mm. Patients were only Table 1. Patient and stone characteristics at baseline
randomized if ESWL resulted in successful fragmentation of the
stone (ie, stone fragmentation to particles ⬍5 mm as observed ESWL Plus
Characteristic ESWL Tamsulosin
by radiography or ultrasonography). Stones that were not suc-
cessfully disintegrated were retreated with 1 or 2 treatment Patients (n) 87 99
sessions. Patients provided written consent before enrollment to Mean age ⫾ SD (y) 51 ⫾ 22 54 ⫾ 20
Sex (n)
the study, which was conducted in accordance with the ethical
Male 54 67
principles of the Declaration of Helsinki. Female 33 32
Stone location
Exclusion Criteria Ureteral 37 40
Patients were excluded if they were pregnant, received antico- Renal 56 53
agulant medication, or had orthostatic hypotension, peptic ul- Mean stone size ⫾ SD (mm)
cer disease, or coagulation disorders. In addition, patients with Ureteral 9⫾5 10 ⫾ 4
Renal 12 ⫾ 7 14 ⫾ 6
known hypersensitivity to tamsulosin were excluded.
Chemical stone composition
Calcium oxalate monohydrate 27 29
Randomization Calcium oxalate dehydrate 31 30
After successful ESWL, the patients were assigned at random to Magnesium ammonium 16 15
1 of 2 medical treatment groups according to their order of phosphate
inclusion in the study and admittance to the clinic. The stan- Mixed 18 20
dard care group was treated with the standard medication ESWL ⫽ extracorporeal shock wave lithotripsy; SD ⫽ standard
regimen, including an antibacterial drug, a corticosteroid (pred- deviation.
nisolone 20 mg/d for 10 days), and a nonsteroidal anti-inflam-
matory drug (diclofenac 100 mg). The second group (ie, the therapy were also assessed. Detailed questions about nausea,
tamsulosin group) received tamsulosin using the oral controlled vomiting, dizziness, headache, stomachache, and other adverse
absorption system at 0.4 mg/d for 1 month, in addition to the events were queried.
standard medication regimen. The investigators were not kept
unaware of the treatment allocation, except for the radiologist
Statistical Analysis
who did the ultrasound check for stone fragment expulsion.
All data were analyzed using the Statistical Package for Social
Sciences (SPSS, Chicago, IL) software. Statistical differences
Diagnostic Methods were calculated using the Student t test or chi-square test. A P
All participants in the present study had the following labora- value ⬍ .05 was considered statistically significant. Only pa-
tory parameters examined: complete blood count, erythrocyte tients who completed the 12-week study period were included
sedimentation rate, creatinine, coagulation time, bleeding time, in the analysis. Based on the data from previous studies, it was
prothrombin time, aspartate aminotransferase, alanine amino- calculated that the sample size had to be 180 to detect a
transferase, and urinalysis. statistically significant difference between the 2 groups in ex-
The diagnostic imaging methods minimally included kidney, pulsion rate at 12 weeks (using an ␣ error level of 5% and a
ureter, and bladder radiography before and immediately after power of 80%).
ESWL and ultrasonography of the urinary tract before and after
ESWL. When needed, intravenous urography and axial com-
puted tomography of the urinary tract were performed. RESULTS
Patients and Baseline Characteristics
Outcome Parameters and Follow-Up From February 2006 to April 2007, 248 patients were
All patients underwent follow-up examinations at 4, 8, and 12
enrolled in the present study. Of these patients, 186
weeks after ESWL. The primary outcome measurement was the
complete stone clearance rate (absence of fragments ⬎3 mm on
(75%) completed the study protocol and were included
ultrasonography) after 12 weeks. Ultrasonography was per- in the statistical analysis. Of the 186 patients, 87 were
formed by 2 radiologists using the same equipment for all allocated to standard care and 99 to tamsulosin 0.4 mg/d
patients. Other efficacy variables included the interval to elim- plus standard care. The patient and stone characteristics
ination of the stone fragments and the percentage of patients per treatment group are listed in Table 1. Ureteral stones
with renal colic. Renal colic was defined as severe pain in the were located in the proximal ureter (n ⫽ 34), the middle
lumbar region radiating toward the urinary bladder and lasting third of the ureter (n ⫽ 18), or the distal ureter (n ⫽ 25).
ⱖ2 hours. Furthermore, the percentage of patients requiring Renal stones were located in the pyelon (n ⫽ 60) or the
rehospitalization for events related to the stones or the study upper pole calices (n ⫽ 26). Patient sex and age, chem-
(rehospitalization rate) was compared between the 2 study ical stone composition, stone dimension, stone localiza-
groups. The reasons for rehospitalization included renal colic
tion, and ESWL power and number of shock waves used
that did not respond to medication taken on outpatient basis for
⬎12 hours or fever ⬎38°C associated with renal colic, or
were comparable between the 2 groups (P ⫽ NS).
otherwise.
The main methods of follow-up were diagnostic imaging Efficacy
(kidney, ureter, and bladder radiography and ultrasonography) No statistically significant difference was found between
and structured interviews of the patients. During these inter- the 2 groups in the incidence of repeat ESWL or endou-
views, adverse events and tolerance of the medical expulsive rologic procedures (Table 2).

1024 UROLOGY 78 (5), 2011

Table 2. Lithotripsy outcomes
ESWL Plus
Characteristic ESWL Tamsulosin
Patients (n) 87 99
Median applied energy during
ESWL (J)
Ureteral 101 109
Renal 68 71
Repeat ESWL (n) 22 24
Auxiliary procedures (n) 4 4
ESWL ⫽ extracorporeal shock wave lithotripsy.
Figure 1. Stone-free rate at 4, 8, and 12 weeks after ESWL
in patients receiving standard care (n ⫽ 87) and patients
receiving tamsulosin oral controlled absorption system 0.4
mg/d combined with standard care (n ⫽ 99).
At 4 and 12 weeks after ESWL, complete elimination
of the stone fragments had occurred significantly more
frequently in the tamsulosin group than in the standard
care-only group (P ⬍ .001 and P ⬍ .05, respectively).
Also, a trend was seen toward a difference between the 2
groups at week 8 (P ⫽ NS). The results are summarized
in Figure 1.
The median interval to complete elimination of frag-
ments was significantly shorter in the tamsulosin group
than in the standard care-only group (39 and 71 days,
respectively; P ⬍ .001). In addition, the proportion of
patients with renal colic was significantly lower and re-
hospitalization occurred significantly less frequently in
patients treated with tamsulosin than in those treated
with standard care alone (P ⬍ .001 and P ⬍ .05, respec-
tively; Table 3).
Safety
The safety profile did not differ significantly between the
2 treatment groups (Table 3). No unexpected adverse
events were reported, only events characteristic for the 2
medication groups, such as variations in blood pressure,
headache, dizziness, gastrointestinal problems, or allergic
reactions, occurred. Drug discontinuation because of al-
lergic reactions or adverse events was not reported by any
patient.
UROLOGY 78 (5), 2011
Table 3. Proportion of patients with renal colic and rehos-
pitalization rate at 12 weeks after extracorporeal shock
wave lithotripsy
Patients (%)
ESWL Plus
Variable ESWL Tamsulosin P Value
Renal colic 68.4 21.7 ⬍.001
Rehospitalization 24.6 6.9 ⬍.05
Hematuria ⬎7 d 13.8 11.1 NS
Fever ⬎38°C 6.9 7.1 NS
Renal hematoma 0 0 NS
ESWL ⫽ extracorporeal shock wave lithotripsy; NS, not signifi-
cant.
COMMENT
The present study examined the beneficial effects and
safety of tamsulosin in patients with renal or ureteral
stones after successful ESWL. In brief, tamsulosin in
addition to standard therapy was significantly more effec-
tive in enhancing the clearance of stone fragments after
ESWL than standard care alone and significantly reduced
the interval to the complete elimination of fragments. At
4 weeks after treatment, 73% of patients allocated to
tamsulosin were free of stone fragments compared with
only 56% of those allocated to standard treatment alone.
By week 12, the stone-free rate had increased to ⬎90% in
the tamsulosin group and about 75% in the standard care
group. The median interval to stone expulsion was 39
days for the patients receiving tamsulosin and 71 days for
those receiving standard care only.
These results are in line with those reported by previ-
ous studies assessing the effect of medical expulsive ther-
apy on stone expulsion.5,6 The interest in medical expul-
sive therapy for urolithiasis has increased considerably
during the past few years. Recently, a systematic review,
including 47 randomized controlled trials, evaluated the
effect of medical expulsive therapy in patients with upper
urinary tract stones.6 Of the 47 studies, 13, including 8
using tamsulosin 0.4 mg/d,7-14 assessed the effect of
␣1-AR antagonists on stone expulsion after ESWL. A
pooled analysis of these studies revealed a statistically
significant effect of ␣1-AR antagonists on stone expul-
sion. ␣1-AR antagonists probably facilitate ureteral stone
expulsion by relaxing ureteral smooth muscle through
␣1-AR blockade, resulting in reduced basal tone and
peristaltic frequency of the ureter without completely
ablating peristaltic activity, which is essential for stone
passage.15
In our study, tamsulosin also had a positive effect on
the rehospitalization rate and the incidence of renal
colic. In the tamsulosin group, the percentages of patients
requiring rehospitalization and those with renal colic
were less than one third of those reported in the standard
care-only group. Although a few studies have previously
shown a positive effect of tamsulosin on the number of
patients requiring hospitalization, this is the first random-
ized trial to assess the rehospitalization rate after ESWL
to date.16-19 Two randomized trials previously assessed
1025
the effect of tamsulosin on renal colic in patients who
underwent ESWL.7,12 In both cases, tamsulosin signifi-
cantly reduced the number of colic episodes. A reduced
risk of rehospitalization and colic pain could considerably
reduce the burden for the patient. In addition, these
positive effects of tamsulosin might also contribute to a
reduction in the economic burden of stone disease for
society.
Although several studies previously assessed the effect
of tamsulosin on stone expulsion after ESWL, the num-
ber of patients included in these studies was low. In the
8 studies included in the systematic review by Seitz et al,6
only 317 patients received tamsulosin 0.4 mg/d after
ESWL. In only 4 studies, tamsulosin was given in addi-
tion to standard therapy. The present study is the largest
to assess the effect of tamsulosin on stone expulsion after
ESWL. In addition, characteristics such as patient sex
and age, stone location, stone dimension, and stone com-
position, and the parameters of ESWL were comparable
between the 2 treatment groups, minimizing bias. More-
over, all patients included in our study were living in
Bulgaria, and data from this part of the world are limited.
It should be emphasized that our study assessed the
efficacy and safety of tamsulosin combined with standard
care (ie, an antibacterial drug, the corticosteroid pred-
nisolone, and the nonsteroidal anti-inflammatory drug
diclofenac). Apart from their anti-inflammatory effect,
corticosteroids have been suggested to facilitate stone
expulsion when used with ␣1-AR antagonists.6 Diclofe-
nac is the recommended treatment to provide pain relief
in patients with renal colic.3 Although theoretically the
use of 2 medications from different therapeutic groups
could lead to unknown interactions and adverse events,
no safety issues were encountered in our study.
A limitation of the present study was that investigators
(except for the radiologist who checked stone fragment
expulsion) were not kept unaware of the treatment allo-
cation, and the patients were not actively contacted if
they missed an appointment. This, plus that the patients
came from all over Bulgaria, implying that the travel
distances were often very long, could explain the rather
high dropout rate of the patients from our study. In
contrast, the open-label allocation and the lack of obli-
gations for the patients provide a good reflection of the
situation in daily clinical care, implying that the results
of our study can be extended to real-life practice.
CONCLUSIONS
The results of the present prospective clinical trial have
confirmed that adjuvant medical expulsive treatment can
improve the outcome of ESWL. Although the level of
evidence for using tamsulosin as a medical expulsive
therapy to facilitate the expulsion of stone fragments
after ESWL is growing, larger, double-blind, randomized
controlled multicenter trials are needed to confirm these
results and to assess the economic benefits of using tam-
sulosin after ESWL.
1026
Acknowledgment. To Ismar Healthcare for assistance in ed-
iting the manuscript; editorial control resides with the authors
and editor.
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UROLOGY 78 (5), 2011