Predictors of non-persistence in women with overactive bladder syndrome.

Persistence is important for the success in the treatment of women with overactive bladder syndrome (OAB). We aimed to identify the predictors of non-persistence in women with OAB after first-line medical treatment. All consecutive women with OAB (n = 608), who underwent urodynamic studies and received first-line medical treatment (5 mg of solifenacin or 25 mg of mirabegron per day) in a referral medical center, were reviewed. Mirabegron (hazard ratio [HR] = 0.711) was associated with a higher persistence rate, compared to solifenacin. Mirabegron treatment (HR = 0.269) was less likely to switch medication; however, a high Urogenital Distress Inventory score (HR = 1.082) was more likely to switch medication. Furthermore, old age (HR = 1.050, especially for ≥ 75 years) and high voided volume (dL, HR = 1.420, especially for voided volume ≥ 250 ml) were associated with added medication at follow-up. Additionally, women with low parity (HR = 0.653, especially for parity ≤ 3) and a low Incontinence Impact Questionnaire (IIQ-7) score (HR = 0.828, especially for IIQ-7 score ≤ 7) were associated with improvement without medication. In conclusion, mirabegron can be considered as the first frontline treatment to increase the persistence rate and decrease the rate of switched medications, compared to solifenacin. In addition, combination therapy or higher-dose monotherapy could be used as the first front-line treatment for women ≥ 75 years of age or with ≥ 250 ml of voided volume.

Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Evaluation of antifungal activity, mechanisms of action and toxicological profile of the synthetic amide 2-chloro-N-phenylacetamide.

Aspergillus niger causes infections such as otitis and pulmonary aspergillosis in immunocompromised individuals. Treatment involves voriconazole or amphotericin B, and due to the increase in fungal resistance, the search for new compounds with antifungal activity has intensified. In the development of new drugs, cytotoxicity and genotoxicity assays are important, as they allow predicting possible damage that a molecule can cause, and in silico studies predict the pharmacokinetic properties. The aim of this study was to verify the antifungal activity and the mechanism of action of the synthetic amide 2-chloro-N-phenylacetamide against Aspergillus niger strains and toxicity. 2-Chloro-N-phenylacetamide showed antifungal activity against different strains of Aspergillus niger with minimum inhibitory concentrations between 32 and 256 µg/mL and minimum fungicides between 64 and 1024 µg/mL. The minimum inhibitory concentration of 2-chloro-N-phenylacetamide also inhibited conidia germination. When associated with amphotericin B or voriconazole, 2-chloro-N-phenylacetamide had antagonistic effects. Interaction with ergosterol in the plasma membrane is the probable mechanism of action.2-Chloro-N-phenylacetamide has favorable physicochemical parameters, good oral bioavailability and absorption in the gastrointestinal tract, crosses the blood-brain barrier and inhibits CYP1A2. At concentrations of 50 to 500 µg/mL, it has little hemolytic effect and a protective effect for type A and O red blood cells, and in the cells of the oral mucosa it promotes little genotoxic change. It is concluded that 2-chloro-N-phenylacetamide has promising antifungal potential, favorable pharmacokinetic profile for oral administration and low cytotoxic and genotoxic potential, being a promising candidate for in vivo toxicity studies.

Analyzing Access and Costs of Oral Medications for Overactive Bladder: Uncovering Disparities.

OBJECTIVE: To report out-of-pocket costs associated with overactive bladder (OAB) medications among Medicare beneficiaries and the uninsured. METHODS: We performed a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data (Q1-2022). FDA-approved medications for OAB were identified. We calculated out-of-pocket costs for Medicare beneficiaries in each Part D prescription benefit phase, average retail price, total yearly costs and discounted prices through cash-pay discount coupons (GoodRx) or online pharmacies like Mark Cuban Cost Plus Drug Company (MCCPDC). We also report plan utilization management requirements. RESULTS: We analyzed 5721 plan formularies for 18 medications. Mirabegron was the only beta-3 agonist (B3). Only Vesicare oral solution (14.3% of plans) and Mirabegron (0.1%) required prior authorization. Many plans required step therapy for selective generic anticholinergics (ACH) (12.4%-43.3%), while the B3 rarely required step therapy (0.6%). Monthly costs varied by coverage phase and averaged $59 for ACHs in the initial coverage phase ($14 in catastrophic; $72 in coverage gap). The monthly cost for the B3 averaged $47 in the initial coverage phase ($26 in catastrophic; $129 in coverage gap). The total yearly cost for generic ACHs ranged from $494 (oxybutynin IR) to $1452 (darifenacin) and the yearly cost for brand-name ACHs ranged from $1175 (Toviaz ER) to $2198 (Oxytrol). The total yearly cost for the B3 was $1283. CONCLUSION: We evaluated coverage, out-of-pocket costs, total yearly costs, and utilization management for OAB medications to make pricing more transparent. While selective medications may be "covered," coverage does not translate into affordable drug prices.

Effects of mirabegron on brown adipose tissue and metabolism in humans: A systematic review and meta-analysis.

BACKGROUND: Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. ß3-adrenergic receptor (ß3-AR) agonists have also gained attention as potential agents for BAT activation and metabolic regulation. Mirabegron, a selective ß3-AR-agonist used clinically for overactive bladder syndrome, has been explored for its utility in metabolic disorders. However, the controversy surrounding the ability of mirabegron to activate BAT to accelerate metabolism requires further investigation. The aim of this systematic review is to characterize comprehensively the impact of mirabegron on human BAT and its metabolism. METHODS: We searched PubMed Central, Web of Science, Embase, and Cochrane Library databases for relevant papers published from the date of database inception to March 2023 for systematic reviews and meta-analyses. We extracted data on primary outcome indicators such as BAT volume, BAT activity, body temperature, and resting energy expenditure (REE), as well as secondary outcome indicators such as heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), non-esterified fatty acids (NEFA), blood glucose, and blood insulin from relevant studies. For studies that did not provide suitable data for meta-analysis, we used narrative data synthesis. For studies that provided suitable data for meta-analysis, we conducted meta-analysis using RevMan 5.4 software. RESULTS: We reviewed 10 papers and included 6 in our meta-analysis. Our findings revealed no significant changes in BAT volume (p = 0.72) or blood glucose (p = 0.52) with mirabegron when compared to the placebo or pre-dose population. However, patients showed significant increases in BAT activity (p < 0.01), blood NEFA (p < 0.01), body temperature (p < 0.01), REE (p < 0.01), HR (p < 0.01), DBP (p < 0.01), SBP (p = 0.25), and blood insulin (p < 0.01). CONCLUSION: Through our meta-analysis of 6 papers, we found that mirabegron has the potential to increase human BAT activity, REE, NEFA content, body temperature, HR, blood pressure, and blood insulin content. These effects may lead to reductions in blood glucose levels in obese/overweight and diabetic patients. Additionally, the activation of BAT by mirabegron could represent a novel approach for treating obesity, diabetes, and cardiovascular disease. TRIAL REGISTRATION NUMBER AND DATE: CRD42023413446, 04/11/2023.

The Role of Ranolazine in Heart Failure-Current Concepts.

Heart failure is a complex clinical syndrome with a detrimental impact on mortality and morbidity. Energy substrate utilization and myocardial ion channel regulation have gained research interest especially after the introduction of sodium-glucose co-transporter 2 inhibitors in the treatment of heart failure. Ranolazine or N-(2,6-dimethylphenyl)-2-(4-[2-hydroxy-3-(2-methoxyphenoxy) propyl] piperazin-1-yl) acetamide hydrochloride is an active piperazine derivative which inhibits late sodium current thus minimizing calcium overload in the ischemic cardiomyocytes. Ranolazine also prevents fatty acid oxidation and favors glycose utilization ameliorating the "energy starvation" of the failing heart. Heart failure with preserved ejection fraction is characterized by diastolic impairment; according to the literature ranolazine could be beneficial in the management of increased left ventricular end-diastolic pressure, right ventricular systolic dysfunction and wall shear stress which is reflected by the high natriuretic peptides. Fewer data is evident regarding the effects of ranolazine in heart failure with reduced ejection fraction and mainly support the control of the sodium-calcium exchanger and function of sarcoendoplasmic reticulum calcium adenosine triphosphatase. Ranolazine's therapeutic mechanisms in myocardial ion channels and energy utilization are documented in patients with chronic coronary syndromes. Nevertheless, ranolazine might have a broader effect in the therapy of heart failure and further mechanistic research is required.

Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease.

BACKGROUND: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. OBJECTIVES: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. METHODS: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. RESULTS: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. CONCLUSIONS: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Persistence of overactive bladder pharmacological treatment in women as reflected from large-scale real-world data of prescription claims: A retrospective cohort study.

INTRODUCTION AND OBJECTIVES: Medical treatments for overactive bladder (OAB) have proven efficacy in controlled trials. However, 1-year treatment persistence is reported to be as low as 25% for anticholinergics and 40% for ß3 agonists. Real-world data on treatment continuation and treatment sequence is limited. Therefore, we aimed to study treatment persistence trends in women initiated on OAB medications. MATERIALS AND METHODS: We used advanced data-mining techniques to query the largest regional provider's medication purchase database, dispensing for patients, for all women initiating OAB pharmacotherapy between 2010 and 2020. Treatment persistence was measured as days in which the patient was in possession of medication and nonpersistence was defined as prescription nonrefilling for 90 days. We employed a Sankey diagram to explore trends in OAB medication acquisition and treatment sequence. We compared treatment persistence using Kaplan-Meier survival curves and pairwise log-rank analysis. RESULTS: Here, 46 079 women made 791 681 unique claims of OAB medications. Only 39% of the patients tried more than one OAB formulation, including dose change. The overall persistence rate for all drugs was 55% in 30 days, 46% in 90 days, and 37% per year. The persistence rate for Mirabegron at 30 days was 54%, 42% at 90 days, and 17% at 1 year. Overall, persistence rates were unchanged when stratifying by the time Mirabegron insurance acceptance into coverage (p > 0.05). CONCLUSIONS: Real-world OAB pharmacotherapy persistence rates are lower than previously reported. The introduction of Mirabegron did not seem to improve these rates or affect the treatment sequence.

Mirabegron and Anticholinergics in the Treatment of Overactive Bladder Syndrome: A Meta-analysis.

OBJECTIVE: To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). DATA SOURCE: Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. DATA COLLECTION: RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. DATA SYNTHESIS: We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. CONCLUSION: Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.

OBJETIVO: Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). FONTE DE DADOS: Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. COLETA DE DADOS: RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. SíNTESE DOS DADOS: Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89­0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48­0,68); 9.375 pacientes; RR: 0,44 (0,35­0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98­1,00)]. CONCLUSãO: Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.

[Assessment of prescribing practices in overactive bladder pharmacotherapy across different specialties of India: a prescription trend analysis].

PURPOSE: To assess the prescribing practices for overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis across different specialties of India. METHOD: s: IQVIA (Quintiles and IMS Health) secondary sales audit (SSA), as well as a prescription audit for antimuscarinics and beta-3 adrenoceptor agonists (mirabegron) from 2014 to 2021, were analyzed. The data includes SSA data of various antimuscarinics like solifenacin, oxybutynin, tolterodine, darifenacin, trospium and mirabegron change in the prescription trend of antimuscarinics and mirabegron across different specialties; prescribers overlap analysis for solifenacin and mirabegron among Indian urologists were also analyzed. RESULTS: Urologists prescription rates of OAB drugs were 65% in 2016 and 54% in 2021. The rate of OAB medication prescription by non-urologist was highest from the surgeon (11%), followed by gynecologists (9%) and consultant physicians (8%) in 2021. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 58% in 2021 whereas for mirabegron, it was 0% in 2016 and 42% in 2021. Solifenacin was most frequently prescribed anticholinergics, followed by oxybutynin, tolterodine, darifenacin, and trospium. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2021. Exclusive prescribers of solifenacin were 748 in 2018 and 739 in 2021 at the urologist, whereas for mirabegron, it was 961 in 2018 and 934 in 2021. The compound annual growth rate for prescription of the last 6 years (from 2016-2021) for solifenacin and mirabegron was -3% and 8% respectively. CONCLUSIONS: Urology remained a top prescribing specialty for OAB drugs, although prescription share increased at surgeon and consultant physician. OAB medicines prescriptions by urologists are shifting from leading antimuscarinic solifenacin to beta-agonist mirabegron. Data from this study will ultimately lead to the OAB medication preference by the specialist that could lead to more advanced OAB management.

Urodynamic parameter improvements after mirabegron vs. antimuscarinics agents in non-neurogenic overactive bladder: a systematic review and meta-analysis of treatment effect.

OBJECTIVE: This review aimed to establish the comparison between mirabegron and antimuscarinic agents through the improvement of the urodynamic study (UDS) parameter among overactive bladder (OAB) populations. MATERIALS AND METHODS: The PRISMA checklist and procedure were utilized to standardize our review of studies from scientific databases published between January 2013 and May 2022 in accordance with the applied eligibility criteria. This study mainly focused on UDS parameter improvement; hence, baseline and follow-up completion were mandatory to be included. The quality of each included study was assessed with the Cochrane risk-of-bias tool in RevMan 5.4.1. RESULTS: We included a total of 5 clinical trials encompassing 430 clinically confirmed OAB individuals. Our meta-analysis demonstrated that the improvement of maximum urinary flow rate (Qmax) was more apparent in the mirabegron arm [mean difference (MD), 1.78 (1.31, 2.26); p<0.05] compared to antimuscarinics arm [MD, 0.02 (-2.53, 2.57); p>0.05) as analyzed in random-effect model (REM) analysis within 95% CI. Similar outcomes were also observed on the other UDS parameters related to the bladder's storage function, e.g., post-void residual (PVR) and detrusor overactivity (DO) cases, with most of the MDs favoring mirabegron. CONCLUSIONS: Mirabegron is superior in improving most of the UDS parameter outcomes compared to the antimuscarinics agents though the current guideline should always refer to symptoms improvement. Emphasizing the role of UDS parameter measurements to objectively confirm a therapeutic effect should be considered in the upcoming studies.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis.

PURPOSE: Ranolazine is used to treat stable angina pectoris, the most common symptom of ischemic heart disease. Appropriate management of chronic stable angina pectoris is essential from both a clinical and an economic view point. METHODS: This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included cost-utility analyses, which compared ranolazine with other standard treatments for treating stable angina pectoris. The search was conducted in PubMed, EMBASE, and Scopus databases. A random-effects model based on the DerSimonian and Laird method was used to pool the incremental net benefit reported in purchasing power parity adjusted US dollars. The modified economic evaluation checklist was used to assess the risk of bias. FINDINGS: The pooled results from 7 selected studies with a time horizon of 1 year show that add-on ranolazine was significantly cost-effective compared with standard treatment, with a pooled incremental net benefit of US$1335 (95% CI, 500 to 2169) but with substantial heterogeneity (I2 = 79.46%). On subgroup analysis, ranolazine was cost-effective from the payers' perspective (US$1975; 95% CI, 1042 to 2908; I2 = 69.23) but not from a societal perspective (US$297; 95% CI, -241 to 715; I2 = 0%)]. There was limited evidence from lower economies. IMPLICATIONS: Pooled evidence suggests that add-on ranolazine therapy is cost-effective for chronic stable angina pectoris up to a 1-year time horizon. There is a lacuna of evidence from low- and middle-income countries and on long-term cost-effectiveness. The current evidence synthesis may provide a macroeconomic point of view for policy makers regarding the direction of ranolazine's cost-effectiveness for evidence-informed policy-making. PROSPERO identifier: CRD42022332454.

The efficacy and safety of medication for treating overactive bladder in patients with Parkinson's disease: a meta-analysis and systematic review of randomized double-blind placebo-controlled trials.

INTRODUCTION AND HYPOTHESIS: The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD). METHODS: Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis. RESULTS: We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy. CONCLUSIONS: Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.

Economic Impact Associated with Patients with Overactive Bladder on Drug Treatment with Mirabegron or Antimuscarinics in Spain.

OBJECTIVE: To assess the economic impact associated with overactive bladder (OAB) patients, treated with mirabegron or antimuscarinics (AM) in Spain, over a 12-month period. METHODS: A probabilistic model (second-order Monte Carlo simulation) was used in a hypothetical cohort of 1000 patients with OAB and a time horizon of 12 months. The use of resources was obtained from the retrospective observational study MIRACAT that included 3330 patients with OAB. The analysis was carried out from the perspective of the National Health System (NHS) including that of society with the indirect cost of abseenteism in a sensitivity analysis. Unit costs were obtained from Spanish public healthcare prices (€ 2021) and from previously published Spanish studies. RESULTS: The annual average savings for the NHS for each patient with OAB treated with mirabegron would be € 1135 (95%confidence interval (CI) € 390; 2421) compared with a patient treated with AM. Annual average savings were maintained in all the sensitivity analyses carried out, ranging from a minimum of € 299 to a maximum of € 3381 per patient. The substitution of 25% of the AM treatments (for 81534 patients) to mirabegron would generate, within 1 year, savings for the NHS of € 92 million (95% CI € 31; 197 million). CONCLUSIONS: According to the present model, the treatment of OAB with mirabegron would generate savings compared with treatment with AM in all scenarios and sensitivity analysis performed, and for the NHS and for society perspectives.

Comparison of Mirabegron and Vibegron in Women With Treatment-Naive Overactive Bladder: A Randomized Controlled Study.

OBJECTIVE: To compare the efficacy and safety of mirabegron versus vibegron in postmenopausal women with treatment-naïve overactive bladder (OAB). METHODS: We conducted a prospective randomized controlled study of women with treatment-naïve OAB. The patients received mirabegron or vibegron at 50 mg daily for 12 weeks by a stratified randomized method. The OAB symptom score (OABSS) and quality of life (QOL) index were evaluated before and 4 and 12 weeks after the treatment. The patients' 3-day voiding diary and postvoided residual urine volumes were evaluated before and 12 weeks after the treatment. RESULTS: Of 213 patients initially enrolled in this study, 199 patients were randomized to the mirabegron group (n = 97) or vibegron group (n = 102). Twelve weeks after the treatment, OABSS, QOL index, the numbers of micturition, urgency episodes, incontinence episodes, and voided volume per 24 hours were significantly improved compared with the baseline in both groups, and there was no significant difference in the rate of change in both groups. The postvoid residual urine volume was not significantly different in the 2 groups at 12 weeks. Discontinuation because of adverse effects was observed in 6.2% of patients in the mirabegron group and 6.8% in the vibegron group, with no significant difference between 2 groups. CONCLUSION: Both mirabegron at 50 mg and vibegron at 50 mg improved OAB symptoms and the parameters of voiding diary equally in postmenopausal women with treatment naïve OAB.

Does metabolic syndrome influence the efficacy of mirabegron treatment in female patients with overactive bladder?

INTRODUCTION AND HYPOTHESIS: We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB). METHODS: Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance. RESULTS: Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39). CONCLUSIONS: Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

Safety and efficacy of ranolazine in hypertrophic cardiomyopathy: Real-world experience in a National Referral Center.

OBJECTIVES: We assessed the efficacy and safety of ranolazine in real-world patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Ranolazine is an anti-anginal drug that inhibits the late phase of the inward sodium current. In a small prospective trial, ranolazine reduced the arrhythmic burden and improved biomarker profile in HCM patients. However, systematic reports reflecting real-world use in this setting are lacking. METHODS: Changes in clinical and instrumental features, symptoms and arrhythmic burden were evaluated in 119 patients with HCM before and during treatment with ranolazine at a national referral centre for HCM. RESULTS: Patients were treated with ranolazine for 2 [1-4] years; 83 (70%) achieved a dosage ≥1000 mg per day. Treatment interruption was necessary in 24 patients (20%) due to side effects (n = 10, 8%) or disopyramide initiation (n = 8, 7%). Seventy patients (59%) were treated with ranolazine for relief of angina. Among them, 51 (73%) had total symptomatic relief and 47 patients (67%) showed ≥2 Canadian Cardiovascular society (CCS) angina grade improvement. Sixteen patients (13%) were treated for recurrent ventricular arrhythmias, including 4 with a clear ischemic trigger, who experienced no further arrhythmic episodes while on ranolazine. Finally, 33 patients (28%) were treated for heart failure associated with severe diastolic dysfunction: no symptomatic benefit could be observed in this group. CONCLUSION: Ranolazine was safe and well tolerated in patients with HCM. The use of ranolazine may be considered in patients with HCM and microvascular angina.

Urobiome changes differ based on OAB treatment in adult females.

INTRODUCTION AND HYPOTHESIS: Representatives of two classes of oral medication are often used to treat urgency urinary incontinence (UUI): solifenacin, an M3-receptor-selective antimuscarinic, and mirabegron, a beta-3 agonist. Two previous asynchronous drug-specific studies suggested different interactions between these medications and the urobiome despite identical methodologies, including recruitment, sample procurement, medication dose escalation strategy, determination of 12-week responders versus nonresponders, and data collection. This analysis compares data from these two studies using a uniform analytic approach. METHODS: Urine was collected aseptically via transurethral catheter from consenting participants for subsequent processing by the Expanded Quantitative Urine Culture (EQUC) protocol in two cohorts (n=50 and n=47) that were demographically similar. Species accumulation curves were generated to compare the total number of unique species detected. Indices that measure richness, evenness, and/or abundance were used to compare alpha (within sample) diversity. The Bray-Curtis Dissimilarity Index was used to determine between sample (beta) diversity. RESULTS: The majority of the 40 species detected in the pre-treatment urobiomes were detected in both cohorts. Both pre-treatment urobiomes were substantially similar in species richness, evenness, and diversity. Differences in pre-treatment urobiomes were associated with treatment response for solifenacin-treated participants only. In contrast, the pre-treatment urobiomes of mirabegron-treated participants were not associated with treatment response. Changes in the post-treatment urobiomes were detected in both cohorts with an increase in richness for both solifenacin (5-mg dose only) and mirabegron. CONCLUSIONS: Pre-treatment urobiome characteristics were associated with treatment response in participants treated with solifenacin, but not mirabegron. Differences exist in urobiome response after treatment with two medications that have known differences in mechanism of action.