In an intention-to-treat analysis, subjective improvement at 12 months was significantly higher in women randomized to midurethral sling surgery than in women randomized to physiotherapy (91% vs 64%, respectively).
Ten percent of patients had adverse events (AEs); all were related to surgery. The most common AEs were hematoma, vaginal epithelial perforation, and bladder perforation.
Notably, women had the option to cross over to the other treatment modality if they desired. In the physiotherapy group, 49% of women elected to cross over to surgery, while 11% of those who underwent midurethral sling surgery elected to cross over to physiotherapy during the 12-month follow-up period. When analyzing results by treatment received, the investigators found that the proportion of women who reported improvement was significantly lower among women who underwent physiotherapy only (32%), versus sling only (94%), or sling after physiotherapy (91%).
This randomized trial was well-designed and included a variety of treatment centers (university and general hospitals) with interventions performed by experienced surgeons (all of whom had performed at least 20 sling surgeries) and physiotherapists educated specifically in pelvic floor physiotherapy. The study population was limited to patients with moderate to severe SUI as defined by the Sandvik severity index.9 Therefore, these results may not be applicable to patients with milder symptoms, for whom physiotherapy has been recommended as first-line therapy with consideration of surgery if physiotherapy fails to sufficiently improve symptoms.7
Women with moderate to severe SUI without significant prolapse or a history of prior incontinence surgery have significantly better outcomes at 12 months after undergoing midurethral sling surgery versus physiotherapy. Physiotherapy carries little to no risk of adverse effects. Women with moderate to severe SUI should be counseled regarding the risks and benefits of both physiotherapy and midurethral sling surgery as initial treatment options.
Because stress and urgency urinary symptoms often present together, it is important to consider urodynamic evaluation to confirm SUI prior to surgery in women with:
• mixed stress and urge symptoms
• a history of a previous surgery for incontinence, or
• poor correlation of physical examination findings to reported symptoms.
Chapple CR, Kaplan SA, Mitcheson D, et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a beta(3)-adrenoceptor agonist, in overactive bladder. Eur Urol. 2013;63(2):296−305.
In the bladder, beta3-receptors located within the detrusor smooth muscle facilitate urine storage by relaxing the detrusor, enabling the bladder to fill.10 The activation of beta3-receptors is thought to increase the bladder’s ability to store urine, with the goal of decreasing urgency, frequency, nocturia, and urgency incontinence. An alternative to anticholinergic medications, mirabegron is a beta3-agonist approved by the US Food and Drug Administration (FDA) in 2012 for clinical use in the treatment of OAB.
Chapple and colleagues aimed to assess the 12-month efficacy and safety of mirabegron in a randomized, double-blind active controlled trial. The primary outcome was incidence and severity of treatment-emergent adverse effects (TEAEs); the secondary outcome was the change in OAB symptoms from baseline to up to 12 months. Patients experiencing OAB symptoms for more than 3 months were eligible and were subsequently enrolled if they averaged 8 or more voids per day and 3 or more episodes of urgency with or without incontinence on a 3-day bladder diary. A total of 2,444 patients were randomly assigned in a 1:1:1 fashion to mirabegron 50 mg daily, mirabegron 100 mg daily, or tolterodine extended release (ER) 4 mg daily.
There was a similar incidence (60% to 63%) of TEAEs across all three groups. The most common TEAEs were hypertension (defined as average systolic blood pressure [BP] >140 mm Hg or average diastolic BP >90 mm Hg at two consecutive visits), UTI, headache, nasopharyngitis, and constipation. The adjusted mean changes in BP from baseline to final visit were less than 1 mm Hg for both systolic and diastolic BP for patients taking both doses of mirabegron, as well as for patients taking tolterodine. The incidence of dry mouth was higher in the tolterodine group than the mirabegron groups. Mirabegron 50 mg daily and 100 mg daily improved incontinence symptoms within 1 month of starting therapy; the degree of improvement was similar to that seen in the patients taking tolterodine ER 4 mg daily.
Related article: New overactive bladder treatment approved by the FDA (August 2012)
This study was well-designed to assess the safety and tolerability of mirabegron versus tolterodine. The doses utilized in the study were at or above the FDA-approved dosage of 25 mg to 50 mg daily for OAB treatment. Although investigators found mirabegron to be a safe alternative to anticholinergic medication, the study was not designed or powered to examine the efficacy of mirabegron versus tolterodine. No formal comparison of efficacy was made between mirabegron or tolterodine, or between the 50-mg and 100-mg doses of mirabegron. Moreover, 81% of participants had been treated with mirabegron in earlier Phase 3 studies, so most were not treatment naïve, limiting the applicability of results.
