European Journal of Cardiovascular Medicine

The life-time risk of developing urinary calculi is between 5% to 12%, affecting men more than women. The rate of spontaneous passage with no medical intervention for a stone of 5 mm or smaller in the proximal ureter is estimated to be 29% to 98%, and in the distal ureter to be 71% to 98%.¹

In recent years, there has been a growing trend in administering medication in addition to analgesia to patients with distal ureteric calculi in order to help with the expulsion of a calculus.² Medical expulsion therapy (MET) has recently emerged as an appealing option for the initial management of ureteral stones. There is a large body of published data, which has shown the efficacy of such a therapy in increasing the expulsion rate and in decreasing the expulsion time of the stones.³

Tamsulosin, an α1-adrenoceptor antagonist, is uroselective for α1A and α1D receptors. This is a very popular and effective medical agent used for Medical Expulsive Therapy (MET). But, recently it has been reported that the α1A adrenoceptor is the main participant in phenylephrine-induced ureteral contraction in human isolated ureter.⁴

A newly introduced drug silodosin, more of an α1A selective adrenoceptor antagonist has shown promising results with fewer side effects and better efficacy. The use of these drugs in the treatment of distal ureteral stones arose from the concept that they could induce a selective relaxation of the ureteral smooth muscle, which could inhibit the ureteral spasms and result in dilatation of the ureteral lumen and passage of ureteric stones.⁵

We conducted a randomised, open label study in Department of Urology, Super Speciality Hospital, Government Medical College, Kadapa and Department of Urology, Government General Hospital, Kurnool Medical College, Kurnool, Andhra Pradesh during the period from July 2023 to June 2024.

All patients provided an informed written consent for participation. By convenience 140 patients were enrolled into the study with 70 in each group. No sample size calculation was done. Patients enrolled in this study were 20 years of age and above. They voluntarily decided to take part in this study and gave their written consent. All patients were having lower ureteral calculi of size ≤ 10 mm on ultrasonography.

Patients with blood creatinine levels more than 2 mg/dL, history of drug allergy, pregnant women or nursing mothers were excluded. A thorough clinical examination was done by a qualified urologist for all patients. The patients were evaluated by an ultrasonography and x-ray KUB. Simple randomization by lot method was done to allot patients alternatively into Tamsulosin and Silodosin groups (n= 70 in each group). The patients from Tamsulosin group were giventamsulosin 0.4 mg/day and the other group silodosin 8mg/day single dose at night. The patients were treated for amaximum period of 4 weeks and observed for stoneexpulsion. The follow-up continued until the patients wererendered stone-free by intervention or spontaneous stoneexpulsion, as was confirmed by the patient for a maximum of4 weeks. The primary outcome was the stone expulsion rateand the secondary outcome was the stone expulsion time.

Stone expulsion rate was defined as number of patients out of total patients enrolled in the study, who had passed stonesafter taking drugs for less than or equal to 4 weeks. Time for stone passage was defined as the number of days from the date of study enrolment to the date when patient’s identifiedtheir stone passage or the date of the follow-up visit when theimaging study no longer detected a visible stone. Follow-up was done weekly or at two weeks interval. Data such asdemographic data, duration of intake of drugs and time takenfor the expulsion of stone were recorded in a specially designed proforma, which was transformed to a master chart and then subjected to statistical analysis. SPSS version 20software was used for statistical analysis. Statistical analysiswas done by using chi-square test, Fisher exact test for qualitative data and student’s ‘t’ test for quantitative data likestone expulsion time.

A total of 140 patients were enrolled in the study. Out of 140 patients, 108 patients completed the study. 16 patients from group tamsulosin and 14 patients from group silodosin were lost for follow-up. Group tamsulosin (54 patients) consisted of 32 men and 22 women (mean age: 34.8 + 12.7 years), group silodosin (56 patients) consisted of 32 men and 24 women (mean age: 36.4 ± 12.7 years). There were no statistically significant differences between the 2 groups in terms of sex, age or stone size (p >0.05).

Table 1: Comparison of Outcome of Tamsulosin according to Gender

Table 2: Comparison of Outcome of Silodosin according to Gender

Table 3: Demographic Details of Patients, Stone Expulsion Rate and Time

Our study showed that in Tamsulosin group, out of 32 male patients 16 had passed stones and out of 22 female patients 14 had passed stones. In silodosin group, out of 32 male patients 26 had passed stones and out of 24 female patients 20 had passed stones, which was statistically not significant. Tamsulosin and silodosin group with stone size ≤ 7 mm did not show a significant difference in stone expulsion rate (p value= 1), whereas > 7 mm achieved statistical significance (p value= 0.01).

As the life-time risk of developing urinary calculi is between 5% - 12%, affecting men more than women, so our study has compared if outcome of drugs is affected by gender of patients. The outcome of tamsulosin and silodosin was found to be not affected by gender of patients.

Urolithiasis is common in the global population, affecting 1%-5% of the population in Asia, 5% - 9% in Europe, 13% in North America and 20% in Saudi Arabia. Small uretericcalculi have higher probability to pass and do not often needsurgical intervention. The most important factors in predicting the likelihood of spontaneous stone passage arestone location and stone size. Ureteral stones account for approximately 20% of urolithiasis cases; approximately 70%of ureteral stones are located in the lower third part of theureter and are known as “distal ureteric stones.⁶

Spontaneous passage depends on stone size, shape, location and associated ureteral oedema. Recently, α-blockers used as MET have replaced minimally invasive procedures as the first line of management for small ureteric stones. The most commonly used α-blocker for MET is tamsulosin, but similar effects have been shown by other α-blockers such as terazosin anddoxazosin indicating a possible class effect. There has beena significant improvement in the medical management of the ureteral calculi with the introduction of effective medical therapeutic agents in the market. The α1A- and α1D-adrenoceptors are the most abundant sub-types in the distal ureter; stimulation of these α1 adrenoceptors leads to increase in both the frequency of ureteric peristalsis and the force of ureteric contractions. However, blockade of these receptors decreases basal ureteric tone, peristaltic frequency and amplitude, leading to a decrease in the intraluminal pressure, while the rate of urine transport increases and thus increasing the chance of stone passage. Highly selectivea1A-adrenoceptor blockers have been developed to minimize the cardiovascular adverse effects, whereas the affinity of silodosin to α1A-AR subtype is about 162-fold and 50-foldgreater than its affinity to α1B- and α1D-AR subtypes.⁷

Alpha blockers are thus recommended by the American Urological Association (AUA) and the European Association of Urology (EAU) for MET of distal ureteral stones less than10 mm in diameter. In our study, the stone clearance rate was significantly higher in the silodosin group when compared with tamsulosin group at 82.1% and 55.5%, respectively (p= 0.04). Our results were in agreement with those of Guptaand co-researchers, who reported stone clearance rates of82% and 58% for silodosin and tamsulosin groups respectively; and also in agreement with those of Kumar and co-researchers who reported stone clearance rates of 83.3%and 64.4% for their silodosin and tamsulosin groups respectively. However, Imperatore and co-researchers reported a non-significant difference of stone clearance rates between silodosin (88%) and tamsulosin (84%).⁸

In our study, stone expulsion rate was calculated for stone size ≤ 7 mm and > 7 mm size. In our study, stone expulsionrate was not significant between silodosin and tamsulosin group with stone size ≤ 7 mm, but stone size > 7 mm showed statistical significance. Also, the mean (SD) stone expulsion time was shorter in the silodosin group vs the tamsulosin group at 16.7 (6.8) vs 19.1 (8.6) days, but could not reach statistical significance.⁹

These results are also in agreement with those of Guptaand co-researchers, who also reported significantly shorter mean (SD) stone expulsion times in the silodosin vs the tamsulosin group at 12.5 (3.5) vs 19.5 (7.5) days, respectively; and also in agreement with Kumar and co-researchers who reported mean (SD) stone expulsion times of 16.5 (4.6) days in the tamsulosin group and 14.8 (3.3) days in the silodosin group. However, Imperatore and co-researchers reported a shorter mean stone expulsion time for both silodosin and tamsulosin of 6.7 and 6.5 days, respectively.¹⁰

We found that silodosin was more effective for distal ureteric calculi of size >7 mm size. We conclude that silodosin is better than tamsulosin in terms of stone clearance rate and stone clearance time for the management of distal ureteric calculi of size <10 mm. We recommend that a conservative approach should be considered as an option in the management of the uncomplicated, small, distal ureteral calculi. Large multicentre trials are required to prove the efficacy and safety of silodosin over tamsulosin.

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