|Year : 2022 | Volume
| Issue : 1 | Page : 19-25
A comparative study of the efficacy of silodosin versus tamsulosin versus oral hydration therapy in medical expulsion therapy for ureteral calculi
Dilip Kumar Pal, Ankit Kumar, Debansu Sarkar
Department of Urology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India
|Date of Submission||19-Jan-2021|
|Date of Decision||26-Jun-2021|
|Date of Acceptance||03-Aug-2021|
|Date of Web Publication||02-Mar-2022|
Prof. Dilip Kumar Pal
Department of Urology, Institute of Postgraduate Medical Education and Research, 244, AJC Bose Road, Kolkata - 700 020, West Bengal
Source of Support: None, Conflict of Interest: None
Purpose: The use of various alpha-receptor antagonists (α-blocker) drugs as medical expulsive therapy (MET) for spontaneous clearance of ureteral calculi of various sizes has been extensive in the last decade by urologists across the world. Among all, α-blocker tamsulosin has been used widely. In contrast silodosin which is recently introduced in the market and more selective alpha-receptor antagonist and cardioselective drug but it has not been used widely as MET. In this study, silodosin (8 mg), tamsulosin (0.4 mg), and oral hydration therapy were compared in terms of efficacy and safety as MET in the management of ureteric stone along with rate of stone clearance, expulsion time, analgesic requirements, and adverse effects for treating ureteral stones size between ≥4 mm and ≤10 mm in diameter. Materials and Methods: Prospective randomized study was conducted between September 2018 and August 2020 with a total of 240 patients (80 patients in each arm) in tertiary care center of eastern India. First group received a single dose of silodosin (8 mg) daily, second group received a single dose of tamsulosin (0.4 mg) daily and third group received oral hydration therapy for 4 weeks. Results: There is no difference in the stone expulsion rate (SER), stone expulsion time (SET), and surgical intervention between tamsulosin, silodosin and oral hydration therapy group for ureteric stones ≤5 mm size. For ureteric stones of size 6 mm–10 mm, silodosin has better SER than tamsulosin with no difference in terms of SET. Analgesic requirement and pain episodes were more in the oral hydration group with no adverse effects (statistically significant). Conclusion: The proportion of passed-out stone was significantly higher among the patients treated with silodosin (65.0%) in comparison to other two groups (P < 0.05) with no difference in SET.
Keywords: Alpha-blockers, silodosin, tamsulosin, ureteric calculi
|How to cite this article:|
Pal DK, Kumar A, Sarkar D. A comparative study of the efficacy of silodosin versus tamsulosin versus oral hydration therapy in medical expulsion therapy for ureteral calculi. Urol Sci 2022;33:19-25
|How to cite this URL:|
Pal DK, Kumar A, Sarkar D. A comparative study of the efficacy of silodosin versus tamsulosin versus oral hydration therapy in medical expulsion therapy for ureteral calculi. Urol Sci [serial online] 2022 [cited 2023 Dec 1];33:19-25. Available from: https://www.e-urol-sci.com/text.asp?2022/33/1/19/338934
| Introduction|| |
Among all urinary tract stones, 22% are ureteric stones, and nearly two-thirds are found in the distal ureter. Ureteric stones are either obstructive or nonobstructive. Obstructive stones can irreversibly damage the kidney in short period. Patients with nonobstructive ureteric calculi may be asymptomatic and incidentally diagnosed. However, symptomatic patients can have episodes of colicky pain, hematuria, or infection.
Managing ureteric calculi requires individualization considering symptoms and complications, including conservative methods such as observation for automatic clearance, medications such as medical expulsive therapy (MET), extracorporeal shock wave lithotripsy, and invasive procedures such as ureterorenoscopic lithotripsy and open or laparoscopic ureterolithotomy. Proper medical history, clinical presentation, laboratory parameters, and renal function, and imaging can determine whether a patient requires medical treatment or urgent surgical intervention (SX).
Being a noninvasive modality with a proven efficacy and high safety profile, MET is preferred by many patients to facilitate the spontaneous expulsion of ureteral stones. Alpha-blockers, calcium channel blockers, and phosphodiesterase inhibitors with or without corticosteroids have been used recently, and these medications have demonstrated their role in spontaneous ureteral stone clearance. Different medications act on the ureter using various mechanisms. Stone size, site, and composition; presence and grade of the obstruction; symptoms; and urinary system anatomy should be considered before determining an appropriate treatment approach.
MET has a proven role in promoting stone passage, thus reducing the need for minimally invasive surgery. Alpha-blockers are the mainstay of MET treatment, and tamsulosin is the most commonly used. The pharmacotherapeutic advantage of tamsulosin is that it has an equal affinity for both α-1A and α-1D receptors. Silodosin has a much higher selectivity for α-1A than for α-1B receptors. The selectivity of silodosin and tamsulosin for the α-1D subtype is similar, but for the α-1A subtype, silodosin has ~ 17-fold higher affinity than does tamsulosin.
Does silodosin have a greater impact on MET than tamsulosin? In this prospective study, we evaluated and compared the efficacy of silodosin versus tamsulosin versus oral hydration therapy in MET for ureteral stones between ≥4 mm and ≤10 mm in size.
We obtained ethical clearance for this prospective study from the Institutional Ethics Committee of IPGME and R, Kolkata, India, dated March 7, 2019 (Memo no. IPGMEandR/IEC/2019/453), and related documents have been submitted herewith.
| Materials and Methods|| |
This prospective study was conducted in the department of urology at a tertiary hospital in eastern India. We enrolled 240 patients from our institution (80 in each group) in this study between September 2018 and August 2020 after approval by the institutional ethics committee. Patients enrolled voluntarily, and we received informed consent from all. We included patients who were ≥18 years old and had unilateral, nonimpacted, nonobstructed, uncomplicated ureteral stones between ≥4 mm and ≤10 mm in size that were visible within 7 days of enrollment on an X-ray kidney/ureter/bladder radiograph (KUB), ultrasound KUB, or noncontrast computed tomography (NCCT KUB).
We confirmed a diagnosis of ureteric calculus on any of the above modalities, but for standardization and to rule out any possible errors among these modalities, we measured the accurate size of the ureteric stone in the transverse and longitudinal axes on NCCT KUB in the axial and coronal reconstruction planes, respectively. We considered the size of the stone as the largest stone in diameter on either the longitudinal or transverse axis. We excluded patients with multiple stones, a solitary kidney, bilateral ureteric stones, persistent renal colic, impaired renal function, Grades 3 or 4 hydronephrosis according to the society for fetal urology (SFU) grading, and any history of previous SX .
Using the SFU grading, we defined Grade 1 hydronephrosis (mild) as dilatation of the renal pelvis without that of the calyces, which also could have occurred in the extrarenal pelvis, and Grade 2 as mild dilatation of the renal pelvis with calyces (pelvicalyceal pattern is retained). Both features are associated with nonimpacted, nonobstructed ureteral stones; hence, we enrolled patients with Grades 1 and 2 hydronephrosis in this study.
We randomly divided the patients into three groups using computerized random sampling. Group 1 received a single dose of silodosin (8 mg) daily, Group 2 received a single dose of tamsulosin (0.4 mg) daily, and Group 3 received oral hydration therapy for 4 weeks [Figure 1].
In cases of ureteric colic, we prescribed 50 mg of diclofenac sodium for analgesia. We used the visual analog scale to assess patients' pain levels. We called the patients every week for follow-up, asking them about episodes of renal colic, analgesic use, time of stone passage, and symptoms associated with adverse medication effects. We advised all patients to increase their water intake to at least 3 L per day and to filter their urine to determine if stone expulsion had occurred.
This study's primary outcome was stone expulsion rate (SER), which was spontaneous stone expulsion without any intervention during the study period. Secondary outcomes were stone expulsion time (SET), number of pain episodes, requirement for analgesics, and adverse events associated with silodosin versus tamsulosin versus oral hydration therapy. We confirmed spontaneous stone passage using X-ray KUB, ultrasound KUB, or NCCT every week and at the end of the 4-week study period. Definitive surgery was scheduled as soon as possible on the basis of our institution's waiting list and at not <2 weeks to facilitate the passage of the ureteric stones by MET.
We performed the data analysis using SPSS Version 20.0 (IBM, Montauk, NY, USA). We expressed the qualitative data variables using frequency and percentage and the quantitative data variables using mean and standard deviation. We used analysis of variance and the Kruskal–Wallis test to compare the three independent groups for the quantitative data variables. We used the Chi-square and Fisher's exact tests use to compare the groups for the qualitative data variables. A P ≤ 0.05 was considered statistically significant.
| Results|| |
We enrolled 240 patients (160 men, 80 women) in the study. The mean patient ages were 33.33, 34.57, and 32.05 years in the silodosin, tamsulosin, and hydration groups, respectively. [Table 1] depicts the baseline patient characteristics in all three study groups. The groups were comparable for mean age, mean stone size, and stone location.
[Table 2] lists the overall results. The SER was significantly higher among the patients treated with silodosin (65.0%) as compared to the other two groups (P < 0.05), and no significant difference occurred between the hydration (51.3%) and tamsulosin groups (46.3%) (P > 0.05). In general, silodosin was superior to tamsulosin and hydration for SER.
In the subgroup analysis for ureteric stones ≤5 mm in size, we found no difference in SER, SET, and SX among the groups. For the SER of ureteric stones 6–10 mm in size, silodosin (silodosin > tamsulosin > hydration) was superior to both tamsulosin and hydration (P = 0.04) [Table 3]. For SET, we found no difference among the groups (silodosin = tamsulosin = hydration) [Table 4].
Pain control was better with silodosin and tamsulosin, and analgesic requirements were higher in the hydration group (62.5%) (P < 0.01). Thus, both silodosin and tamsulosin were effective for controlling ureteric colic.
We found dizziness in 4 (5%) patients treated with tamsulosin. Retrograde ejaculation was significantly higher in 12 (15%) patients treated with silodosin, but no adverse effects occurred in the patients treated with hydration [Table 2] (P = 0.002). We observed that, in the presence of significant hydronephrosis (complicated ureteric stones), SER was not affected by MET and was statistically significant (P = 0.001) [Table 5].
|Table 5: Subgroup analysis of passage of stone in presence of hydronephrosis|
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After stratifying the participants using stone size and location to evaluate the efficacy of the medication, for the ureteric stones of ≤5 mm in size, we found no differences in SERs among the 3 groups; however, for the stones 6–10 mm in size, silodosin had a better SER for the lower and middle ureteric stones (P value significant) but not for upper ureteric stones (clinically significant but statistically insignificant) [Table 6].
|Table 6: Stratification of participants using both stone size and location to the evaluate the efficacy of medication|
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| Discussion|| |
Various factors can affect the management of ureteral stones. Stone-related factors include location, size, composition, and obstruction severity; clinical factors include symptom severity, patients' expectations, the presence of urosepsis, solitary kidney status, and aberrant anatomy. Technical factors involve available instruments and health care costs.
The 2020 European Association of Urology guidelines have reported that the maximum benefit and efficacy of MET is for patients with distal ureteral stones of >5 mm in size. The indications for SX in cases of ureteric stones of ≤10 mm in size are refractory pain episodes, impaired renal function, a solitary kidney, and clinical evidence of urosepsis or perinephric urine extravasation. In the absence of these indications, conservative management with periodic evaluation is preferred.
Adrenergic receptor (AR) agonists have a stimulatory effect on the ureteral smooth muscle, and 3 types of ARs are expressed in the human ureter with the following order of abundance: α-1D > α-1A > α-1B. The α-1A subtype is located in the lower ureter, bladder neck, and prostate; its concentration is constant from the upper to lower ureter, but the prevalence of α-1D keeps increasing from the upper to lower ureter. α-1A ARplays an important role in phenylephrine-induced ureteral contraction, increasing contraction force and ureteric peristalsis frequency. It also decreases basal tone, leading to selective relaxation of the ureteral smooth muscle; reduces peristaltic amplitude and frequency; decreases intraluminal pressure; increases water transport rate; and thus, increases the chances for stone expulsion.
Recent studies have reported excellent results with MET for distal ureteral calculi using α-1 blockers. Doxazosin was among the first nonselective α-blockers used successfully as MET for distal ureteric stones in late 1990s. Since then, a paradigm shift has occurred in the management of ureteral calculi, with the introduction of more uroselective drugs such as tamsulosin and silodosin in the past decade.
Tamsulosin preferentially blocks α-1A and α-1D ARs and has a 10× greater affinity than that for α-1B AR. Various studies have demonstrated that the use of tamsulosin as MET can increase SER, decrease ureteric colic, reduce SET, and decrease analgesic needs when compared to a placebo.,,
Silodosin is highly selective for α-1A AR, with a 162-fold greater affinity than α-1B AR and about a 50-fold greater affinity than for α-1D AR. The use of silodosin as a substitute for tamsulosin has been encouraging due to its more uroselective nature and fewer adverse effects.
The first prospective randomized study evaluating the use of silodosin in the management of ureteric stones of ≤10 mm in size was done by Itoh et al. A comparison of the efficacy of the selective α-1D AR naftopidil and the selective α-1A AR silodosin in the management of symptomatic ≤10-mm ureteral stones was performed by Tsuzaka et al. Dell Atti compared the effectiveness of silodosin and tamsulosin in the expulsion of distal ureteral stones measuring 4–10 mm in size in 136 patients, finding a significant increase in SER in the patients treated with silodosin (80.3%) as compared to those treated with tamsulosin (61.2%; P = 0.003) with no severe complications, but retrograde ejaculation was reported more often in the silodosin patient group. In a study with 100 patients, Gupta et al. have concluded that silodosin may be superior to tamsulosin in distal ureteral stone (<10 mm) expulsion, finding that the SERs in the tamsulosin and silodosin groups were 58% and 82%, respectively (P = 0.008), with a mean SER of 19.5 days and 12.5 days, respectively (P = 0.01).
To the best of our knowledge, our study is the first to compare tamsulosin, silodosin, and oral hydration therapy in the context of MET for conservative management of ureteric stones at all locations (upper, middle, lower). We also reported an SER significantly higher in patients treated with silodosin than with tamsulosin and hydration (65.0%, 46.3%, and 51.3%, respectively) without a significant difference in SET. For ureteric stones ≤5 mm in size, we found no differences in SER, SET, and SX among the tamsulosin, silodosin, and hydration groups. For those 6 mm–10 mm in size, silodosin was superior in SER.
Our data show that for ureteric stones 6–10 mm in size, silodosin had a better SER for lower and middle ureteric stones but not for upper ureteric stones. One explanation could be due to the higher selectivity and affinity of silodosin with α-1A (silodosin has 17× more affinity for α-1A than does tamsulosin).
In the presence of hydronephrosis, SER was not affected by MET [Table 5]. Adverse effects differ considerably between the available α-blockers. Our results demonstrate that dizziness was the most common side-effect in the tamsulosin group, whereas retrograde ejaculation was associated with silodosin.
| Conclusion|| |
MET with silodosin is a safe and viable option for ureteric calculi. For smaller stones of ≤5 mm in size, we found no difference among the silodosin, tamsulosin, and hydration groups in SER, SET, and SX . For ureteric stones 6–10 mm in size, the more selective α-blocker silodosin was superior to tamsulosin in SER for the lower and middle ureteric stones but not for the upper ureteric stones.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]