Background: Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a β3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points - mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naïve patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability.
Methods: Patients were randomized to placebo, mirabegron 50 or 100 mg, or tolterodine extended release (ER) 4 mg orally, once-daily, for 12 weeks. For the post hoc analysis, the primary patient population was divided into the following subgroups: (1) patients who had not received any prior antimuscarinic OAB medication (treatment-naïve) and (2) patients who had received prior antimuscarinic OAB medication. The latter subgroup was further subdivided into patients who discontinued due to: (3) insufficient efficacy or (4) poor tolerability. Analysis of the co-primary efficacy endpoints by subgroup was performed using analysis of covariance with treatment group, subgroup, sex, geographical region, and subgroup-by-treatment interaction as fixed factors; and baseline value as a covariate.
Results: Mirabegron, 50 mg and 100 mg once-daily, demonstrated similar improvements in the frequency of incontinence episodes and micturitions in OAB patients who were antimuscarinic-naïve and who had discontinued prior antimuscarinic therapy. While mirabegron demonstrated improvements in incontinence and micturition frequency in patients who had discontinued prior antimuscarinic therapy due to insufficient efficacy, the response to tolterodine was similar to that of placebo.
Conclusion: In this post hoc subgroup analysis, mirabegron provided treatment benefits in OAB patients who were antimuscarinic treatment-naïve and in patients who had received prior antimuscarinic treatment.
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http://dx.doi.org/10.1186/1471-2490-13-45 | DOI Listing |
J Korean Med Sci
January 2025
Division of Cardiology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
Background: The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium. Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
February 2025
Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona, United States.
Autonomic dysfunction is associated with cardiovascular and neurological diseases, including hypertension, heart failure, anxiety, and stress-related disorders. Prior studies demonstrated that late gestation exposure to dexamethasone (DEX) resulted in female-biased increases in stress-responsive mean arterial pressure (MAP) and heart rate (HR), suggesting a role for glucocorticoid-mediated programming of autonomic dysfunction. The present study investigated the influence of sympathetic (SYM) or parasympathetic (PS) blockade on cardiovascular function in male and female rat offspring of mothers injected with DEX in utero [ (GD) -].
View Article and Find Full Text PDFNeurobiol Learn Mem
January 2025
Department of Psychology, The University of Texas at Austin, Austin TX 78712, United States; Department of Neurology, The University of Texas at Austin, Austin TX 78712, United States; Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin TX 78712, United States. Electronic address:
The ability to choose between options that differ in their risks and rewards depends on brain regions within the mesocorticolimbic circuit and regulation of their activity by neurotransmitter systems. Dopamine neurotransmission in particular plays a critical role in modulating such risk-taking behavior; however, the contribution of other major modulatory neurotransmitters, such as acetylcholine, is not as well-defined, especially for decision making in which the risk associated with more rewarding outcomes involves adverse consequences. Consequently, the goal of the current experiments was to examine how cholinergic signaling influences decision making involving risk of explicit punishment.
View Article and Find Full Text PDFInt J Chron Obstruct Pulmon Dis
December 2024
AstraZeneca, Cambridge, UK.
Background: We evaluated the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β-agonist (ICS/LAMA/LABA) triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual LAMA/LABA and ICS/LABA therapies in patients with chronic obstructive pulmonary disease (COPD) and phenotypic features of asthma (bronchodilator reversibility and elevated blood eosinophils), but no asthma diagnosis, for whom treatment guidelines are limited.
Patients And Methods: KRONOS (NCT02497001) and ETHOS (NCT02465567) enrolled patients with moderate-to-very-severe COPD, no current asthma diagnosis, and either ≥0 (KRONOS) or ≥1 (ETHOS) moderate/severe exacerbations in the prior year. This pooled post hoc analysis evaluated trough forced expiratory volume in 1 second (FEV) and FEV area under the curve from hours 0 to 4 (AUC) change from baseline over 12-24 weeks, moderate/severe exacerbation rates, and St George's Respiratory Questionnaire (SGRQ) total score over 24 weeks with ICS/LAMA/LABA (BGF 320/14.
Ophthalmic Physiol Opt
January 2025
School of Physics, Clinical & Optometric Sciences, Centre for Eye Research Ireland, Sustainability & Health Research Centre, Technological University Dublin, Dublin, Ireland.
Purpose: This study compared the efficacy of cyclopentolate hydrochloride at 10-, 20- and 30-min post-instillation in White 6- to 7-year-olds, with and without prior instillation of proxymetacaine hydrochloride. The primary aim was to determine if accurate autorefraction values can be obtained sooner than the current standard of 30-min post-cycloplegia. The secondary aim was to investigate whether proxymetacaine hydrochloride enhances the efficiency of cyclopentolate.
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