Wagg Adrian, Nitti Victor W, Kelleher Con, Castro-Diaz David, Siddiqui Emad, Berner Todd
a University of Alberta , Edmonton , Canada ;
b New York University , USA ;
Curr Med Res Opin. 2016;32(4):621-38. doi: 10.1185/03007995.2016.1149806. Epub 2016 Feb 17.
Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.
Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.
Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.
Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.
对于患有多种共病且正在服用多种药物的老年人而言,膀胱过度活动症(OAB)的治疗颇具挑战。抗毒蕈碱药物(如索利那新、非索罗定)和β3肾上腺素能受体激动剂(米拉贝隆)疗效相似;然而,抗毒蕈碱药物可能会引发副作用,导致患者依从性差,并加重抗胆碱能负担,尤其是对于正在服用其他具有抗胆碱能特性药物的患者。米拉贝隆的作用机制与抗毒蕈碱药物不同,具有不同的耐受性特征,且不会加重抗胆碱能负担。本综述的目的是比较和对比抗毒蕈碱药物与米拉贝隆在老年患者中的耐受性特征,为临床实践提供参考。
通过检索PubMed,确定了关于抗毒蕈碱药物治疗老年患者OAB的前瞻性试验或回顾性亚组分析。描述了在三项为期12周的试验和一项为期1年的试验的汇总分析中,米拉贝隆在≥65岁和≥75岁患者中的耐受性数据及亚组分析结果。
与米拉贝隆相比,抗毒蕈碱药物引发的包括口干和便秘在内的抗胆碱能不良事件(AE)更为常见。在≥65岁的患者中,在12周内,服用4毫克托特罗定缓释片(ER)出现口干的发生率比服用25毫克或50毫克米拉贝隆高6倍,在1年内,服用托特罗定ER出现口干的发生率比服用50毫克米拉贝隆高3倍。米拉贝隆的中枢神经系统不良反应发生率较低。一项关于米拉贝隆心血管安全性的系统评价未发现其在≥65岁患者的治疗剂量下对血压或脉搏率有任何临床显著影响。
在老年患者中,米拉贝隆的耐受性特征比抗毒蕈碱药物更有利,可能具有更好的效益风险比,因此可被视为老年患者抗毒蕈碱药物的替代选择。