|Year : 2019 | Volume
| Issue : 4 | Page : 175-181
To compare the efficacy of tamsulosin and tolterodine in double-J stent-related symptoms: A prospective randomized trial
Abhay Mahajan, Dhruti Amlani
Department of Urology, MGM Medical College and Hospital, Aurangabad, Maharashtra, India
|Date of Submission||18-Jan-2020|
|Date of Acceptance||21-Jan-2020|
|Date of Web Publication||29-Apr-2020|
Dr. Abhay Mahajan
Department of Urology, MGM Medical College and Hospital, N6, Cidco, Aurangabad 431003, Maharashtra, India.
Source of Support: None, Conflict of Interest: None
Background: Stent-related symptoms affect nearly 80% of patients with indwelling ureteral stents. Alpha blockers relieve flank pain by blocking alpha-adrenergic receptors and relaxing the smooth muscles of ureter, trigone, and prostatic urethra, thus reducing bladder outlet resistance and voiding pressure, whereas mechanism of anticholinergic drugs involves relief of involuntary bladder contractions that are mediated by muscarinic receptors. We have compared alpha blocker and anticholinergic drugs in reducing stent discomfort. Materials and Methods: The study was conducted from March 2017 to February 2018. A total of 100 patients with unilateral double-J ureteral stenting were randomized, postoperatively into two groups: tamsulosin 0.4mg daily (Group I) and tolterodine 4mg daily (Group II). Results: The mean age was 39.1 years in Group I and 38.0 years in Group II. The male:female ratio in Group I and Group II was 1.38:1 and 1:1, respectively. There was statistically significant difference in urinary symptom score, pain score, and general health score between the two groups in favor of Group I (tamsulosin 0.4mg) at 1week post-stenting and 4 weeks (at stent removal). Conclusion: Oral medication, with uroselective alpha blockers, in patients with indwelling stents reduces stent-related symptoms and negative impact on quality of life.
Keywords: Double-J stent, tamsulosin, tolterodine, Ureteral Stent Symptom Questionnaire
|How to cite this article:|
Mahajan A, Amlani D. To compare the efficacy of tamsulosin and tolterodine in double-J stent-related symptoms: A prospective randomized trial. MGM J Med Sci 2019;6:175-81
|How to cite this URL:|
Mahajan A, Amlani D. To compare the efficacy of tamsulosin and tolterodine in double-J stent-related symptoms: A prospective randomized trial. MGM J Med Sci [serial online] 2019 [cited 2020 Jun 7];6:175-81. Available from: http://www.mgmjms.com/text.asp?2019/6/4/175/283459
| Introduction|| |
The double-J (DJ) ureteral stent has been an indispensable tool in the urologist’s surgical armamentarium since its first description by Zimskind et al. Stent-related discomfort and morbidity is believed to affect over 80% of patients with indwelling ureteral stents. A study by Auge et al. reported that 98% of responders performed ureteroscopic stone surgery in their routine practice, of which two-third of urologists would place a stent more than 50% of the time and 13% would always place a postoperative stent, even though intolerance to the stent was the most significant problem experienced by up to 98% of patients. In spite of growing evidence of well-conducted randomized controlled prospective trials showing safety of not leaving a ureteral stent post-uncomplicated urologic procedure, many urologists still place stents in majority of urologic surgeries. In patients with indwelling stents, most common stent-related symptoms include irritative voiding symptoms such as frequency (50%–60%), urgency (57%–60%), dysuria (40%), incomplete emptying (76%), flank (19%–32%) and suprapubic pain (30%), and incontinence and hematuria (25%).,, Various assessment tools such as International Prostatic Symptom Score (IPSS), Quality of Life Questionnaires, and Overactive Bladder Questionnaire (OAB-q) have been described and used in randomized control trials (RCTs) to assess the prevalence and severity of stent-related symptoms caused by indwelling ureteral stents and its negative impact on patient’s quality of life. However, Joshi et al., reported on the first study to objectively evaluate and develop Ureteral Stent Symptom Questionnaire (USSQ), a comprehensive, reliable, and psychometrically valid, multidimensional measure to evaluate symptomatology associated with ureteral stents. The USSQ consists of 38 items examining six sections: urinary symptoms, pain, general health, work performance, sexual matters, and additional problems. As we transition into an era of medicine that focuses on patient experience and quality of life, it is critical to use the available evidence to optimize comfort and satisfaction in patients who require ureteral stent. Various modifications in the field of stent engineering have been conducted to identify ideal stent material, size, shape, and novel stent designs such as bioabsorbable, drug-eluting, and self-expanding mesh stents. Few studies have shown that appropriate stent length is an important factor affecting stent-related morbidity, with longer stents crossing the midline causing more severe stent-related symptoms. No other variations in stent size, shape, material, and design have shown any consistent effect on stent-related symptoms and quality of life. Hence, various pharmacological agents such as uroselective alpha-antagonists, anticholinergics, combination therapies with alpha blockers and anticholinergics, nonsteroidal anti-inflammatory drugs, and intravesical therapies have been studied to alleviate stent-related symptoms. Of all the pharmacological drugs, alpha-antagonists have been the most studied agents in various well-conducted RCTs and have shown a clear and consistent beneficial effect in patients with indwelling ureteral stents.
The aim of this study was to compare the efficacy and safety of tamsulosin (selective alpha-1 blocker) versus tolterodine (anticholinergic agent) monotherapy using USSQ as the assessment tool in patients with unilateral DJ stents in situ.
| Material and methods|| |
Study population and design
A prospective randomized study was conducted between March 2017 and February 2018. The present randomized trial is the parallel group, two-arm, superiority trial with 1:1 allocation ratio. The randomization of the patients of this study in two groups was performed by using computer-generated random-number table.
A total of 100 patients, who underwent unilateral DJ stenting, following urological procedures such as extracorporeal shockwave lithotripsy (ESWL), ureterorenoscopy (URS), percutaneous nephrolithotomy (PCNL), and acute obstructive uropathy, were enrolled in the study. Ethical clearance was taken from the Institutional Ethics Committee of MGM Medical College and Hospital, Aurangabad after approval of study protocol.
Inclusion and exclusion criteria for patients
The inclusion criteria of the study were as follows:
- All patients above 18 years of age undergoing unilateral DJ stenting following aforementioned urological procedures.
- Patients willing to participate in study and who signed written valid informed consent.
The exclusion criteria of the study were as follows:
- Pregnant women.
- Patients with bilateral DJ stents, stents placed following open urologic procedures, long-term stents, previous history of ureteral stenting, forgotten stents, use of alpha blockers, and/or anticholinergic agents and those with known bladder pathology, overactive bladder, benign prosthetic hyperplasia, and urinary tract infection were excluded from the study.
This study was conducted in the Department of Urology, MGM Medical College and Hospital, Aurangabad, Maharashtra, India.
Routine preoperative evaluation was carried out for the planned operative procedures. Polyurethane ureteral stents were used in all patients. The length and caliber of stents were adjusted for each patient according to patient’s somatometric characteristics. The stent was inserted under fluoroscopic control in all cases. Routinely, X-ray abdominal film was performed for all patients before discharge to confirm proper stent position. Stents were removed at 4 weeks in all the patients enrolled for the study. The outcome was observed at 1 week and at the end of 4 week in the study.
To assess the stent-related morbidity, all patients completed validated USSQ, 1 week after the DJ stent insertion and at 4 weeks (stent removal). USSQ consists of five sections, including urinary symptoms, body pain, general health, work performance, sexual matters, and additional problems. Each section has a summary score; higher scores correspond to worse outcomes. Visual Analog Pain Scale (VAPS) was used to assess pain graded from 0 (no symptoms) to 10 (symptoms of maximum severity).
Patients were randomized into two groups using computer-generated random-number table. Group I (n = 50) received oral dose of tamsulosin 0.4mg once daily at bedtime and Group II (n = 50) received tolterodine 4mg once daily for 4 weeks. All consenting patients were fully informed regarding potential side effects of tamsulosin and tolterodine.
Data were analyzed by using Statistical Package for the Social Sciences software program, version 24.0 (SPSS, Chicago, Illinois). A t test was used to determine the comparisons between the mean of two groups in terms of urinary symptom index score, pain index score, general health index score, work performance score, and sexual matters at 1 and 4 weeks post DJ stenting. A P value was checked at 5% level of significance.
| Results|| |
All 100 enrolled patients completed the study [Figure 1]. Group I (tamsulosin) consisted of 50 patients (mean age = 39.1 ± 14.4) and Group II (tolterodine) consisted of 50 patients (mean age = 38.0 ± 15.1). No statistically significant differences were observed between the two groups regarding patient’s demographics and treatment indications [Table 1].,
Of the 100 patients with unilateral DJ stent inserted, 52 patients underwent URS, 26 patients underwent PCNL, and 12 patients underwent ESWL. On assessment using USSQ, patients receiving tamsulosin (Group I) experienced statistically significant overall lower urinary symptom score at 1 week (P = 0.008) and at 4 weeks (P = 0.0049) [Figure 2] as compared to tolterodine (Group II). The pain index score was significantly less in Group I at 1 week (P = 0.008) and at 4 weeks (P = 0.022) as compared to Group II [Figure 3]. The general health index score (quality of life) was significantly less, reflecting better general health in patients under Group I at 1 week (P = 0.013) and at 4 weeks (P = 0.028) [Figure 4]. However, there was no statistically significant positive impact on patient’s work performance between the two groups at 1 and 4 weeks. Also, no statistically significant difference was observed in sexual matters between the two groups at 1 and 4 weeks. None of the patients in either group complained of any additional stent-related problems. No patients had to discontinue medications because of side effects or underwent stent removal before the due date. To summarize, assessment of stent-related symptoms using USSQ confirmed superiority of alpha blocker (tamsulosin) in overcoming stent-related urinary symptoms and pain along with better general health index score as compared to anticholinergic agent (tolterodine) [Table 2]., , ,
|Table 2: Ureteral Stent Symptom Questionnaire (USSQ) of patients in groups|
Click here to view
| Discussion|| |
Placement of indwelling ureteral stents has become a routine urological practice, as it prevents urinary tract obstruction, help drainage of urine, allow ureteric mucosa to heal faster after ureteric injury, help dilate the ureter, and facilitate in small sized ureteric stone passage. Treatment strategies in management of stent-related symptoms can be classified into two different approaches: prevention of stent-related symptoms and management of stent-related symptoms. For the first category, accurate stent indications and improvements in both stent design and structures have been the focus. For the second category, pharmacology has focused on minimizing the motor and sensory bladder response to presence of stent.
A study by Haleblian et al. suggested that stenting following an uncomplicated ureteroscopy does not lower the complication rates or rehospitalization and results in increased treatment cost. Second factor that helps in preventing stent-related symptoms is proper stent positioning and appropriate stent length. A meta-analysis by Dellis et al., which reviewed 11 RCTs in the field of stent engineering, concluded that although there have been many advances in stent composition and design, the ideal stent is yet to be engineered. By contrast, oral alpha blockers have shown greatest reduction in stent morbidity. Many RCTs, using pharmacological agents such as alpha blockers, anticholinergics, nonsteroidal, anti-inflammatory drugs, and intravesical therapies, have shown clear and consistent beneficial effects of uroselective alpha-1 blockers such as tamsulosin and alfuzosin in improving stent-related symptoms. Of all the oral pharmacological agents, alpha-1 blockers have been most widely used and studied for relief of stent-related symptoms with proven efficacy in various RCTs. Alpha-adrenergic receptors (alpha-1a and alpha-1d) are present in distal ureter, bladder trigone, and proximal urethral smooth muscle. Selective alpha blockers, such as tamsulosin, selectively inhibit alpha-1a- and alpha-1d-mediated contraction of distal ureter, trigone, and proximal ureteral smooth muscles. Relaxation of these smooth muscles decreases bladder outlet resistance and voiding pressures, thereby decreasing renal urine reflux and improving urinary symptoms and pain related to DJ stent.,
Damiano et al. conducted an RCT with 75 patients receiving 0.4mg tamsulosin versus placebo in patients who underwent stent placement after URS. Patient’s symptoms were assessed using USSQ and results favored tamsulosin group with significant improvement. Wang et al. studied 154 patients with DJ stents placed after URS and randomized them into two groups receiving 0.4mg tamsulosin versus placebo for 2 weeks. Patients were assessed using USSQ and IPSS. Results showed significant reduction in urinary symptoms score of USSQ with tamsulosin. Yakoubi et al. performed meta-analysis of four RCTs with 341 patients who were assessed by USSQ. Alfuzosin was used in three trials and tamsulosin in one trial. The results favored both these agents toward reducing the urinary symptoms and pain score of USSQ. Similarly, in a meta-analysis, Lamb et al. reviewed five RCTs (three with 10mg alfuzosin and two with tamsulosin) with 461 patients overall and compared symptoms based on USSQ. All five studies showed reduction in urinary symptoms and body pain score of USSQ.
RCT by Dellis et al. assessed the effect of two different alpha blockers, tamsulosin 0.4mg and alfuzosin 10mg using USSQ in patients with indwelling ureteral stents. The results showed overall statistically significant lower urinary symptom score and pain with positive influence on general health score, sexual matters, and quality of life in patients receiving either of the alpha blockers. No difference was observed in various outcomes between the two alpha blockers.
Singh et al.  randomized 60 patients to receive tamsulosin 0.4mg versus placebo in patients with indwelling ureteral stents. Stent-related symptoms were assessed using USSQ and IPSS. Results showed decrease in urinary symptoms and pain, improvement in work performance, decrease in IPSS, improvement in general health, sexual matters, and quality of life with tamsulosin. Thus, concluding that tamsulosin is well tolerated, safe, effective, and significantly beneficial in reducing stent-related symptoms. Similarly, in our study, patients receiving tamsulosin 0.4mg showed decrease in urinary symptoms and pain with improvement in general health score of USSQ. Anticholinergic agents are commonly used in practice to relieve stent-associated LUTS and stent discomfort. Few dedicated studies have investigated their use in stent-related symptoms. Potential benefits have been theorized through extrapolation from benign prostatic hyperplasia studies. Efficacy data of anticholinergics for stent-related symptoms have been inconsistent, but given their ubiquity in urological practice, they are almost routinely used to manage stent discomfort. They are typically well tolerated for the short-term course, whereas the stent is indwelling. It is important to discuss potential side effects of oral pharmacotherapy with combination of selective alpha blockers and anticholinergic agents. Use of anticholinergics in elderly patients may cause worsening of urinary symptoms, affecting their quality of life and add to their dissatisfaction. In older men with coexisting bladder outlet obstruction, these agents can cause exacerbation of outlet obstruction and worsen stent-induced flank pain from high-pressure reflux. Results with RCTs have been equivocal for combination therapy with alpha blockers and anticholinergics and therefore combination therapy may be used at discretion of the provider.
Park et al. randomized 52 patients into three groups: alfuzosin 10mg, tolterodine extended release, and placebo. Assessment was performed using USSQ. Both tolterodine and alfuzosin showed improvement in urinary symptoms and pain score of USSQ. However, no significant difference was observed between the two drugs. Shalaby et al.evaluated 327 patients randomized into four groups: placebo, tamsulosin, solifenacin, and combination therapy. Assessment was performed using IPSS, OAB-q, and VAPS. Results showed combination therapy better than either agent alone. Sivalingam et al. randomized 80 patients into two groups: Group I receiving combination therapy with tamsulosin and tolterodine versus tamsulosin alone. Assessment was performed using USSQ and no statistically significant difference was observed between the two groups. Zhou et al. conducted meta-analysis of efficacy of alpha blocker, anticholinergics, and combination therapy in stent-related symptoms of 1408 patients and a statistically significant difference was observed in urinary symptoms and pain of USSQ, IPSS, QOL, and VAPS in favor of alpha blocker and anticholinergics alone versus control group.
A study by Park et al. included 112 patients randomized by 2 × 2 factorial design into four groups: Group A receiving placebo, Group B receiving tamsulosin 0.2mg, Group C receiving solifenacin 5mg, and Group D receiving combination therapy. Evaluation of results was performed at 2 weeks using USSQ. Results showed no significant beneficial effects with either of the four groups. To the best of our knowledge, none of the studies have compared efficacy of tamsulosin versus tolterodine monotherapy in relieving stent-related symptoms using USSQ. In our study, we have randomized 100 patients into two groups, receiving either tamsulosin 0.4mg or tolterodine 4mg to evaluate the efficacy of selective alpha blocker versus anticholinergic mono therapy in relieving stent-related symptoms, using USSQ and VAPS as assessment tools. Results were in favor of tamsulosin as compared to tolterodine in controlling stent-related symptoms.
| Conclusion|| |
Our study indicates that oral medication with uroselective alpha-blocker monotherapy, in patients with indwelling stents, reduces stent-related symptoms and negative impact on quality of life as compared to anticholinergic agents.
Ethical policy and institutional review board statement
Ethical approval for this study was obtained by the Institutional Ethics Committee of MGM Medical College and Hospital, Aurangabad after approval of study protocol (Protocol no. MGM-ECRHS/2016/56. 15.02.2016).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]