This study is the first to look at inflammatory cytokines, histological changes in the bladder mucosa, and their impact on lower urinary tract complaints by comparing the efficacy of mirabegron 50 mg/day and tamsulosin 0.4 mg/day in patients with ureteral stents installation.

This is a double blind, prospective, randomized clinical trial of patients treated with unilateral ureteral stents. Patients were divided randomly into three groups (placebo/ tamsulosin 0.4mg/ mirabegron 50mg). Blood, urine, and bladder mucosal biopsies were collected before placement and when the ureteral stent was removed. Lower urinary tract symptoms (LUTS) were assessed using the USSQ-urinary symptoms following ureteral stent placement. Data were analyzed using the Kruskal-Wallis test with p-value ≤ 0.05, then tested with pairwise comparisons.

Of the 78 research subjects, only 50 completed the trial (figure 1). There was a significant relationship between the degree of bladder mucosal inflammation and LUTS (p<0.05), as well as an increase in blood serum and urine IL-6 (p<0.05). Mirabegron and tamsulosin had the same effectiveness (p=0.337) and significantly inhibited changes in the degree of bladder mucosal inflammation better than placebo (p=0.001 and p=0.021). Mirabegron is better than tamsulosin and placebo (p = 0.000) and tamsulosin is better than placebo (p = 0.05) in reducing LUTS. Mirabegron was better than tamsulosin and placebo (p=0.036 and p=0.007) in reducing serum IL-6 levels, but mirabegron was only effective than placebo in urine (p=0.007). There were no side effects from the medication during this study.

Inflammation of the bladder mucosa has a direct impact on bladder function in the form of lower urinary tract disorders.
Interleukin-6 can worsen the inflammatory response in interstitial cystitis and IL-6 antagonists can reduce the inflammatory response in bladder mucosal.
In the group receiving Mirabegron therapy, there were significant changes in the condition of LUTS when compared to tamsulosin and placebo. The same was also found in the group that received tamsulosin therapy when compared to placebo. Mirabegron and tamsulosin reduce post-ureteral stent complaints, reduce OAB complaints, lower USSQ scores, and improve quality of life.
Mirabegron was better than tamsulosin and placebo in reducing serum IL-6 levels but in the urine mirabegron only effective than placebo. These results are under the mechanism of action of mirabegron which can inhibit the increase of IL-6 through several pathways and has anti-inflammatory power through antioxidant effects by directly inhibiting NADPHox-mediated ROS production and inducing the expression of the enzyme catalase which is the main scavenger of H2O. (Figure 2)

Mirabegron has been proven to be more effective in treating lower urinary tract complaints than tamsulosin and can be considered the main therapy in patients with ureteral stent placement. However, tamsulosin can be an alternative for treating lower urinary tract complaints. Although mirabegron and tamsulosin can reduce the effects caused by ureteral stents (stent-related symptom), however, the use of ureteral stents needs to be more selective in patients undergoing surgery.