The efficacy and safety of adrenergic alpha-antagonists combined with PDE5 inhibitors in the medical expulsive therapy for unilateral distal ureteral stones: a systematic review and meta-analysis.

BACKGROUND: Distal ureteral stones are a common urological condition, causing significant morbidity. While medical expulsive therapy (MET) using α-adrenergic receptor antagonists (α-ARAs) or phosphodiesterase-5 (PDE5) inhibitors has been widely studied, the efficacy and safety of their combination remain debated. This study aimed to evaluate the efficacy and safety of this combination therapy compared with α-ARAs alone.

METHODS: A systematic search was conducted on PubMed, Embase, the Cochrane Library, Web of Science, and Chinese databases to identify clinical studies published up to November 02, 2025, involving patients with distal ureteral stones treated with PDE5 inhibitors in combination with α-ARAs.All analyses were performed using the Cochrane Collaboration Review Manager software (RevMan 5.4).

RESULTS: A total of eight randomized controlled trials (RCTs) involving 1,202 patients were included, with 1,029 patients ultimately enrolled in the meta-analysis. For distal ureteral stones, the stone expulsion rate (SER) was significantly higher in the combination therapy group than in the α-ARA monotherapy group [risk ratio (RR) =1.25, P<0.001]. The mean stone expulsion time was also significantly shorter in the combination group [standardized mean difference (SMD) =-0.73, P<0.001]. In terms of pain episodes, combination therapy showed a trend toward reducing the number of pain attacks and the need for analgesics. However, the pooled analysis for pain episodes was limited by substantial heterogeneity. Additionally, there were no significant differences between the two groups in terms of adverse events such as headache, dizziness, or hypotension. However, an association with a higher trend of back pain was observed [odds ratio (OR) =1.64, P=0.02], which lost statistical significance in the sensitivity analysis (P=0.06).

CONCLUSIONS: This meta-analysis indicates that compared with α-ARAs monotherapy, combination therapy significantly improves the SER, shortens stone expulsion time, and reduces the need for analgesics. The pooled analysis for pain episodes was limited by substantial heterogeneity and must be interpreted with caution. Regarding safety, there were no significant differences between the two groups for most adverse events; however, an association with a higher risk of back pain was observed, a finding that must be interpreted with caution.