Department of Surgery, Western University, London, ON, Canada.
ICES, London, ON, Canada.
BJU Int. 2020 Jul;126(1):183-190. doi: 10.1111/bju.15040. Epub 2020 Mar 19.
To determine if there is an increased risk of dementia among patients with overactive bladder (OAB) starting an anticholinergic medication compared to those starting a beta-3 agonist.
We conducted a population-based, retrospective, matched cohort study using linked administrative data from Ontario, Canada from 2010 to 2018. We matched 47 324 new users of anticholinergic medications (oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, trospium) to 23 662 new users of a beta-3 agonist medication (mirabegron); all of the included medications are only indicated for the treatment of OAB. We measured 75 baseline variables (including comorbid conditions, recent medications, and prior healthcare utilization) and used these to create a propensity score; groups were similar across all measured variables after matching. The primary exposure was the class of OAB medication (anticholinergic or beta-3 agonist). The primary outcome was dementia using a validated administrative data definition.
The most common anticholinergics used were tolterodine (40%), oxybutynin (29%) and solifenacin (26%). The median (interquartile range [IQR]) prescription duration of anticholinergics was 30 (30-170) days. The median (IQR) prescription duration of a beta-3 agonist (mirabegron) was 64 (30-317) days. There was an increased risk of dementia among anticholinergic users compared to beta-3 agonist users (hazard ratio 1.23, 95% confidence interval 1.12-1.35). There was a significant effect modification based on both gender and age; men and those aged ≤75 years on anticholinergics had the highest risk of dementia relative to similar beta-3 agonist users.
The use of anticholinergic medications among patients with OAB was associated with an increased risk of new-onset dementia compared to beta-3 agonist users. These results address the potential protopathic bias present in other studies on this topic and support the association between anticholinergic medication use and dementia.
确定与使用β3 激动剂相比，开始使用抗胆碱能药物的膀胱过度活动症（OAB）患者发生痴呆的风险是否增加。
我们使用来自加拿大安大略省的 2010 年至 2018 年的链接行政数据进行了一项基于人群的回顾性匹配队列研究。我们将 47324 名新使用抗胆碱能药物（奥昔布宁、托特罗定、索利那新、达非那新、非索罗定、曲司氯铵）的患者与 23662 名新使用β3 激动剂药物（米拉贝隆）的患者进行匹配；所有纳入的药物仅用于治疗 OAB。我们测量了 75 个基线变量（包括合并症、近期药物治疗和既往医疗保健利用情况），并使用这些变量创建了倾向评分；匹配后两组在所有测量变量上相似。主要暴露因素是 OAB 药物类别（抗胆碱能药物或β3 激动剂）。主要结局是使用经过验证的行政数据定义的痴呆。
最常用的抗胆碱能药物为托特罗定（40%）、奥昔布宁（29%）和索利那新（26%）。抗胆碱能药物的中位（四分位距[IQR]）处方持续时间为 30（30-170）天。β3 激动剂（米拉贝隆）的中位（IQR）处方持续时间为 64（30-317）天。与β3 激动剂使用者相比，抗胆碱能药物使用者发生痴呆的风险增加（风险比 1.23，95%置信区间 1.12-1.35）。基于性别和年龄存在显著的效应修饰；与相似的β3 激动剂使用者相比，使用抗胆碱能药物的男性和年龄≤75 岁的患者痴呆风险最高。
与β3 激动剂使用者相比，OAB 患者使用抗胆碱能药物与新发痴呆的风险增加相关。这些结果解决了该主题其他研究中存在的潜在前馈偏倚问题，并支持抗胆碱能药物使用与痴呆之间的关联。
