Cardiovascular safety of mirabegron in patients treated for spinal cord injury- or multiple sclerosis-induced neurogenic detrusor overactivity

Krhut J1, Wohlfahrt P2, Pudich J3, Borovicka V4, Bilkova K5, Sykora R1, Mokris J4, Cifkova R2, Zachoval R4

Research Type

Clinical

Abstract Category

Neurourology

Abstract 107
ePoster 2
Scientific Open Discussion ePoster Session 8
Friday 20th November 2020
13:20 - 13:25 (ePoster Station 3)
Exhibition Hall
Detrusor Overactivity Pharmacology Spinal Cord Injury Multiple Sclerosis Prospective Study
1. Department of Urology, University Hospital, Ostrava, Czech Republic, 2. Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer Hospital, Prague, Czech Republic, 3. Department of Cardiology, University Hospital, Ostrava, Czech Republic, 4. Department of Urology, 3rd Faculty of Medicine of Charles University and Thomayer Hospital, Prague, Czech Republic, 5. Spinal Cord Rehabilitation Unit, Rehabilitation Center, Kladruby, Czech Republic
Presenter
J

Jan Krhut

Links

Abstract

Hypothesis / aims of study
Beta-3- adrenergic agonist mirabegron has been introduced into the treatment of idiopathic overactive bladder (iOAB) in 2012. It´s safety and efficacy has been confirmed in large number of randomized clinical studies.[1] There is an increasing body of evidence supporting the use of mirabegron in the treatment of neurogenic detrusor overactivity (NDO). Although mirabegron has overall favorable safety profile, there is a potential for this drug to affect a cardiovascular (CV) system. Hypertension is the most frequently reported adverse event (AE) occuring in about 9-10% of patients treated with mirabegron for iOAB. Tachycardia, palpitations and arrhytmias were also reported.[2] The CV effect could prove especially significant in NDO patients due to disturbance in the vegetative innervation. This is especially prevalent in those with SCI above T6 level, i.e. above the splanchnic sympathetic outflow. The aim of this communication is to report the analysis of CV safety of mirabegron in patients with SCI or MS.
Study design, materials and methods
Briefly, 78 patients were enrolled into the study, 71 subjects were randomized. Sixty six patients were eligible to be included into the final statistical analysis. Forty nine of them suffered from NDO due to suprasacral SCI, while 17 suffered from NDO due to MS. Eleven patients were previously treated for hypertension and one for arrythmia. After signing the informed consent, patients received placebo for two weeks single-blind run-in period. Eligible subjects were randomized, 1:1 ratio, for 4 weeks of active treatment with mirabegron 50 mg (Group A) or placebo (Group B) in double-blind manner. We recorded CV safety variables as measured by resting ECG, 24 hours ECG monitoring, 24 hours blood pressure monitoring and echocardiography. All reported variables were assessed at randomisation (baseline) and at the end of study. 
Changes in time and differences between groups were assessed using non-parametric Kruskal-Wallis test, p ≤ 0.05 was considered statistically significant.
Results
Baseline demographic and clinical characteristics were similar among mirabegron and placebo group. 
There were no statistically significant changes from baseline to end of treatment found in safety variables, in neither group, except of prolongation of QT interval in placebo group (p=0.0328) as recorded by resting ECG. No significant difference between the groups A and B, in any of the variables, was observed. Individual CV safety variables are shown in Table 1 and 2. A single study drug-related AE was recorded (3.13%). One female patient with cervical SCI experienced palpitation starting 4 days after being randomised to the active arm. This AE was considered moderate and patient terminated the study prematurely. The AE resolved immediately after withdrawal of the study drug.
Interpretation of results
The therapy of NDO with mirabegron was well tolerated. In this vulnerable population, our data did not show higher incidence or severity of CV AEs, compared to those reported in iOAB patients.
Concluding message
Our data strongly support the hypothesis that mirabegron can be safely used in the treatment of patients with SCI- and MS-induced NDO.
Figure 1 Table 1: Results – safety variables as measured by resting ECG and 24hours ECG and blood pressure monitoring
Figure 2 Table 2: Results – safety variables as recorded by echocardiography
References
  1. Chapple CR, Cardozo L, Nitti VW, et al. Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol Urodyn. 2014; 33: 17-30.
  2. Rosa GM, Ferrero S, Nitti VW, et al. Cardiovascular safety of ß3-adrenoceptor agonists for the treatment of patients with overactive bladder syndrome. Eur Urol. 2016; 69: 311-23.
Disclosures
Funding This study was supported by Research grant by Astellas Pharma ISR CZ-110-RG-14. Astellas Pharma provided placebo for this study. Sponsor was not involved in the design and conduct of the study; collection of the data; management of the data; analysis; interpretation of the data; and preparation, review and approval of the abstract. Clinical Trial Yes Registration Number EudraCT 2014–002592-29. RCT Yes Subjects Human Ethics Committee Institutional Review Board of University Hospital Ostrava Helsinki Yes Informed Consent Yes