Overactive bladder (OAB) is a common condition, with symptoms including urinary urgency and frequency with or without urge urinary incontinence (UUI). Among adults aged ≥76 years, 51% of women and 49% of men report experiencing OAB symptoms at least sometimes.¹ When weighing treatment options for older adult patients with OAB, it is especially important to consider their comorbidities and current medications, as well as any other potential risks of treatment.

American Urological Association guidelines recommend behavioral therapy, with or without pharmacological management, including anticholinergics or β₃-adrenergic receptor agonists, as first-line treatment for OAB.² While anticholinergics may be effective for some patients, they can result in bothersome and persistence-limiting side effects such as constipation and dry mouth.² More concerning for older adults with OAB, a recent study found an increased incidence of falls/fractures³ and a meta-analysis of 6 studies⁴ suggested an increase in dementia risk in patients treated with anticholinergics. The American Geriatrics Society Beers Criteria recommend reducing or avoiding unnecessary anticholinergics in older adults because of risks of confusion, dry mouth, constipation, and other anticholinergic-related effects.⁵

β₃-adrenergic receptor agonists treat OAB through a distinct mechanism of action from anticholinergics. Vibegron is a β₃-adrenergic receptor agonist approved in 2020 for the treatment of OAB, based in part on evidence from EMPOWUR, an international, phase 3, randomized, controlled trial that randomly assigned patients to once-daily vibegron 75 mg, placebo, or active control (tolterodine 4 mg extended release) for 12 weeks.⁶ Importantly, 42.9% of patients in EMPOWUR were ≥65 years of age. In EMPOWUR, treatment with vibegron was associated with reduced daily micturitions, urgency episodes, and UUI episodes relative to placebo at week 12. Adverse events (AEs) with incidence ≥2% in the vibegron arm and greater than with placebo were headache (4.0% vs 2.4%), nasopharyngitis (2.8% vs 1.7%), diarrhea (2.2% vs 1.1%), and nausea (2.2% vs 1.1%).

Vibegron was also assessed in a 40-week extension trial, in which patients who received vibegron or tolterodine in EMPOWUR continued on the same treatment for an additional 40 weeks, whereas patients who received placebo were randomized 1:1 to vibegron or tolterodine.⁷ Similar to the 12-week trial, 46.5% of patients in the extension study were ≥65 years of age. Results from the EMPOWUR extension trial were similar to the primary study. Improvements in micturitions, urgency episodes, and UUI episodes were maintained over 52 weeks of vibegron treatment, with no meaningful differences between vibegron and tolterodine in the incidence or severity of AEs.

A subanalysis of the EMPOWUR trial was conducted to assess the efficacy and safety of vibegron in 628 patients aged ≥65 years, including a subset of 179 patients aged ≥75 years.⁸ Patients aged ≥65 and ≥75 years experienced reductions in mean daily micturitions, urgency episodes, and UUI episodes, similar to the overall EMPOWUR population (see Figure; see Varano et al for the complete data⁸). At week 12, among patients aged ≥65 years receiving vibegron, 50.0% had a ≥75% reduction in UUI episodes and 38.7% had a ≥50% reduction in urgency episodes, compared with 29.8% and 28.8% of patients receiving placebo, respectively. The incidence of AEs among patients aged ≥65 and ≥75 years receiving vibegron was generally similar to those receiving tolterodine and the overall study population. Dry mouth, a common anticholinergic AE, occurred more frequently with tolterodine than with vibegron.

In EMPOWUR patients ≥65 years of age, the efficacy and safety of vibegron were similar to the results from the overall study population.⁸ Vibegron treatment reduced daily micturitions, UUI episodes, and urgency episodes in older adults after 12 weeks. Likewise, older adults who received vibegron experienced AEs at similar rates to the overall study population. These results suggest that the efficacy and safety of vibegron in older adults with OAB are consistent with its label.

Older adults are at increased risk of experiencing cardiovascular events; thus, it is important to assess whether any new medication carries a risk of causing or exacerbating hypertension. Notably, adults ≥65 years of age in EMPOWUR experienced AEs of hypertension at similar rates to the overall population, and treatment with vibegron did not increase the incidence of hypertension relative to tolterodine or placebo.⁸ Furthermore, a sensitive ambulatory blood pressure monitoring study found that vibegron treatment was not associated with elevated blood pressure, even in patients who were ≥66 years of age or those with preexisting hypertension, compared with placebo.⁹ Taken together, these results suggest that vibegron may be particularly useful to treat OAB symptoms in older adults with hypertension.

Older adults with OAB are also more likely than those without OAB to take multiple medications to treat comorbid conditions, so it is important to assess the potential for drug-drug interactions when considering a new medication, particularly when using multiple anticholinergics to limit the increased risk of cognitive decline, delirium, and falls or fractures.¹⁰ Importantly, vibegron does not inhibit CYP2D6, limiting the possibility of interactions with numerous medications that are CYP2D6 substrates and that may be prescribed to treat conditions that commonly cooccur with OAB, such as cardiovascular disease and depression. This may make vibegron a useful treatment for patients with polypharmacy.

Dysphagia may be common among older adults. Crushing vibegron is supported by its prescribing information; a clinical study has shown that vibegron can be crushed and administered with applesauce without meaningful changes to its pharmacokinetics.¹¹ Vibegron may be a valuable alternative for older adults with swallowing difficulties, particularly in the long-term care setting.

Overall, the available clinical data support vibegron use in older adults with OAB. The EMPOWUR trial enrolled a substantial population of adults ≥65 years of age, and a subgroup analysis indicated that efficacy and safety in adults aged ≥65 years was similar to the overall trial population.⁸ Using anticholinergic medications to treat OAB may be inappropriate for many older adults due to risks including incident dementia and falls. Vibegron should be accessible for most older adults through Medicare Part D, making it a practical option for anticholinergic deescalation for many patients. The clinical characteristics of vibegron—including its nonanticholinergic mechanism of action, absence of hypertension risk, and absence of CYP2D6 inhibition, along with the option to safely administer as a crushed tablet—make it a valuable treatment option for older adults with OAB.

Acknowledgments

Joseph Kruempel, PhD, CMPP, of The Curry Rockefeller Group, LLC (Tarrytown, New York), provided medical writing and editorial support.

Funding

The EMPOWUR trial and vibegron ambulatory blood pressure monitoring trial were funded by Urovant Sciences. Medical writing and editorial support in the preparation of this manuscript were provided by Urovant Sciences (Irvine, California).

Conflicts of Interest

The author is a consultant for Astellas, AzuraBio, UroCure, and Urovant Sciences; is an investigator and meeting participant/lecturer for Astellas and Urovant Sciences; and holds other interests in AzuraBio and UroCure.