Safety and efficacy of an α1-blocker plus mirabegron compared with an α1-blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: a systematic review and network meta-analysis

Aim: Antimuscarinics and the beta 3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and alpha(1)-adrenoreceptor antagonists (alpha(1)-blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an alpha(1)-blocker plus mirabegron with an alpha(1)-blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. Methods: Included records had to be from a parallel-group, randomized clinical trial that was >= 8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an alpha(1)-blocker plus OAB agent with an alpha(1)-blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Q(max)). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. Results: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the alpha(1)-blocker plus mirabegron and alpha(1)-blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the alpha(1)-blocker plus mirabegron group compared with the alpha(1)-blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Q(max). For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the alpha(1)-blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. Conclusion: This systematic review and meta-analysis showed that an alpha(1)-blocker plus mirabegron and an alpha(1)-blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.