Supplementary Material for: Efficacy and Safety of Muscarinic Antagonists Combined with Adrenergic alpha-Antagonists in the Medical Expulsion Therapy for Distal Ureteral Stone: A Meta-Analysis

Introduction: Lower ureteral stones, due to their proximity to the bladder, frequently cause irritation symptoms and voiding disturbances. The efficacy of combining adrenergic alpha-antagonists with muscarinic antagonists in improving stone expulsion and alleviating lower urinary tract symptoms (LUTS) remains uncertain. This meta-analysis aims to evaluate the clinical benefit of such combination therapy for distal ureteral calculi. Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and major Chinese databases through October 2024. Only randomized controlled trials comparing combination therapy with monotherapy were included. The quality of evidence was assessed using the GRADE framework, and meta-analyses were performed using RevMan 5.3 software. Results: Eight RCTs comprising 800 patients were included. Combination therapy significantly improved stone expulsion rates compared to either alpha-blockers alone (RR = 1.13; p = 0.04) or muscarinic antagonists alone (RR = 1.53; p <0.00001). It also reduced pain episodes (MD = –0.75; p <0.0001) and severity (VAS), and improved urgency symptoms (USS) at 3 and 7 days. No significant difference in stone expulsion time was observed. Constipation and dry mouth were more common in the combination group. Conclusion: Combination therapy with alpha-blockers and muscarinic antagonists improves stone expulsion and symptomatic relief in patients with lower ureteral stones <10 mm, without significantly affecting stone passage time, but at the cost of more anticholinergic side effects.