Anticholinergic drugs are often avoided in elderly patients with overactive bladder (OAB) due to concerns regarding cognitive impairment and other adverse effects. While β3 agonists are recommended as first-line therapy for the elderly in several guidelines, including those in Japan, clinical evidence specifically focusing on the "very elderly" is still limited. Vibegron is a highly selective β3 agonists with minimal drug-drug interactions. Following our previous report on mirabegron (HOKUTO study), this study (HOKUTO 2) aimed to evaluate the efficacy and safety of vibegron in OAB patients aged 80 years and older, with a particular focus on its impact on cognitive function and frailty.

This was a prospective, single-arm, multicenter observational study. Patients aged ≥ 80 years diagnosed with OAB were enrolled and received 50 mg of vibegron once daily for 12 weeks. The primary endpoints were changes from baseline to 12 weeks in the OAB Symptom Score (OABSS) and International Prostate Symptom Score (IPSS). To assess safety and overall well-being, we evaluated the Vulnerable Elders Survey (VES-13) for frailty, the Mini-Mental State Examination (MMSE) for cognitive function, blood test results, 12-lead electrocardiography (QTcF), and post-void residual urine (PVR) volume.

Twenty patients (median age: 83 years; range: 80–93 years) completed the study. Vibegron significantly improved the total OABSS (p < 0.05), with significant improvements in sub-scores for urgency and urge urinary incontinence. Total IPSS, IPSS-QOL index, and IPSS storage sub-scores also showed significant improvements. Regarding safety, there were no significant changes in VES-13, MMSE, or QTcF scores throughout the 12-week period. Although a significant increase in PVR was observed, no cases of acute urinary retention were reported. The four patients who showed a PVR > 100 mL had pre-existing risk factors for voiding dysfunction.

From this study, vibegron for the elderly is effective for storage symptoms same as mirabegron. In safety evaluation, vibegron showed significant increase in PVR. However, cases with relatively high residual urine volumes were included in this study. Vibegron is considered to have very high receptor selectivity. Then, it was considered that both the effects and the side effects on the bladder might be more likely to occur.

Vibegron 50 mg was effective and well-tolerated in very elderly OAB patients aged 80 years and older. Crucially, the treatment did not worsen cognitive function or frailty. While clinicians should monitor residual urine volume in patients with baseline voiding dysfunction, vibegron represents a safe and effective therapeutic option for the oldest-old population.

1)	Nakagomi H. et al. Mirabegron for overactive bladder in frail patients 80 years or over (HOKUTO study). BMC Urol. 2022 Mar 21;22(1):40. doi: 10.1186/s12894-022-00989-7.