Cardiovascular effects of antimuscarinic agents and beta3-adrenergic receptor agonist for the treatment of overactive bladder

ABSTRACT

Introduction: Overactive bladder (OAB) syndrome is common in the general population, particularly in elderly patients. Antimuscarinic drugs (AMs) are considered the mainstay pharmaceutical treatment of OAB whereas β3-adrenoceptor agonists, such as mirabegron, represent a good alternative. Owing to the important role of muscarinic and β3 receptors in cardiovascular (CV) tissue and to the fact that OAB patients often have CV comorbidities, the safety-profile of these drugs constitute an important challenge.

Area covered: The aim of this review is to evaluate the CV effects of AMs and mirabegron in OAB. A systematic literature search from inception until December 2017 was performed on PubMed and Medline.

Expert opinion: AMs are generally considered to have good CV safety profile but, however, they may cause undesirable adverse events, such as dry mouth, constipation. CV AEs are rare but noteworthy, the most common CV consequences related to the use of these drugs are constituted by an increase in HR and QT interval. Mirabegron has similar efficacy and tolerability to AMs but causes less adverse events, with either modest hypertension and modest increase in HR (<5 bpm) being the most commonly reported.

KEYWORDS:

• Antimuscarinics
• cardiovascular adverse effects
• heart rate
• heart rate variability
• hypertension
• Mirabegron
• QT prolongation

Article highlights

• Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgent urinary incontinence (UUI), and is usually associated with increased daytime frequency and nocturia. OAB often involves elderly people, who often present various cardiovascular (CV) comorbidities.

• Antimuscarinics (AMs) represent the most commonly used drugs in the context of OAB. Eight different drugs are currently marketed for pharmacological management of OAB: darifenacin hydrobromide, fesoterodine fumarate, imidafenacin, oxybutynin chloride, propiverine hydrochloride, solifenacin succinate, tolterodine tartrate and trospium chloride.

• The most common CV adverse effects associated with the use of AMs are represented by increase in heart rate (HR) and QT interval prolongation. Only three cases of serious QT prolongation and polymorphic ventricular tachycardia (TdP) were reported with the use of solifenacin.

• Mirabegron, a selective β-3 adrenoceptor agonist represents a good alternative for the treatment of OAB. Mirabegron presented similar efficacy and tolerability to AMs in phase II and III trials, but with reduced side effects characterized by modest hypertension and an increase in HR < 5 bpm.

• The potential impact of AMs and mirabegron on cardiac function should be taken in consideration by physician especially in older patients who are likely to present CV risk factor and other comorbidities.

• Despite the safe pharmacological profile of AM drugs and mirabegron, a clinical and ECG monitoring might be useful especially in selected patients such as those aged> 80 years or with CV comorbidities.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

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Funding

This paper has not been funded.