Department of Urology and The Landon Center on Aging, University of Kansas School of Medicine, Kansas City, KS, USA.
College of Pharmacy, Purdue University, Lafayette, IN, USA.
BMC Geriatr. 2020 Mar 18;20(1):109. doi: 10.1186/s12877-020-1474-7.
Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebo-controlled study (PILLAR; NCT02216214) described the efficacy and safety of mirabegron, a β-adrenoreceptor agonist, for treatment of wet OAB in patients aged ≥65 years. This pre-planned analysis aimed to measure differences in cognitive function between mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA).
Outpatients aged ≥65 years with wet OAB were randomized 1:1 to mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved.
Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the mirabegron group (-0.2 [0.1]) or the placebo group (-0.1 [0.1]).
Treatment with mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo.
NCT02216214 (prospectively registered August 13, 2014).
抗毒蕈碱药物常用于治疗膀胱过度活动症（OAB），但接触具有抗胆碱能特性的药物，如抗毒蕈碱药物，与认知功能不良影响有关。一项 4 期安慰剂对照研究（PILLAR；NCT02216214）描述了米拉贝隆（一种β肾上腺素受体激动剂）治疗≥65 岁湿型 OAB 患者的疗效和安全性。这项预先计划的分析旨在使用轻度认知障碍的快速筛查工具——蒙特利尔认知评估（MoCA），衡量米拉贝隆与安慰剂之间认知功能的差异。
≥65 岁有湿型 OAB 的门诊患者按 1:1 随机分为米拉贝隆或安慰剂组，按年龄（<75/≥75 岁）分层。没有关于认知状态的排除标准。随机分配到米拉贝隆的患者最初每天接受 25mg，根据患者/研究者的判断，在第 4/8 周后可选择增加至 50mg/天。在基线和治疗结束时（第 12 周）进行 MoCA 检测。研究方案经独立伦理委员会/机构审查委员会批准。
在≥1 次接受研究药物的 887 名随机患者中，72.3%为女性，79.5%为白人，28.1%年龄≥75 岁。所有患者均至少有一种合并症，94.3%至少接受一种伴随药物治疗。三分之一的患者有精神疾病史，最常见的是抑郁症（17.2%）、失眠（15.7%）和焦虑症（11.4%）。米拉贝隆组和安慰剂组的基线平均（标准误差，SE）MoCA 总分分别为 26.9（0.1）和 26.8（0.1）。在基线/治疗结束时可获得 MoCA 数据的患者中，米拉贝隆组和安慰剂组分别有 27.1%（115/425）和 25.8%（106/411）的患者存在认知功能障碍（MoCA 总分<26）。米拉贝隆组（-0.2[0.1]）和安慰剂组（-0.1[0.1]）的调整后 MoCA 总分从基线到治疗结束时均无统计学意义的变化。
在≥65 岁的患者中，使用米拉贝隆治疗 12 周并未导致认知功能不良，这一点可以通过 MoCA 进行测量。此外，在年龄较大的 OAB 试验人群中，认知功能随时间的变化模式似乎与接受安慰剂的患者不同。
NCT02216214（2014 年 8 月 13 日前瞻性注册）。
