Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, Texas, USA.
Division of Geriatric and Palliative Medicine, McGovern Medical School at UTHealth, Houston, Texas, USA.
Int J Geriatr Psychiatry. 2021 May;36(5):684-696. doi: 10.1002/gps.5467. Epub 2020 Nov 18.
The differential muscarinic receptor selectivity could cause selective antimuscarinics to offer advantages over nonselective agents with respect to adverse effects. The objective was to examine the comparative risk of falls/fractures and all-cause hospitalizations among older adults with dementia and overactive bladder (OAB) using nonselective and selective antimuscarinics METHODS/DESIGN: A retrospective cohort study design was conducted among older patients with dementia and OAB using incident antimuscarinics. The primary exposure was classified as nonselective (oxybutynin, tolterodine, trospium, and fesoterodine) and selective (solifenacin and darifenacin). Cox proportional-hazards regression using inverse probability of treatment weighting (IPTW) evaluated the risk of falls/fractures and all-cause hospitalizations within 6 months of nonselective and selective antimuscarinic use.
The study cohort consisted of 13,896 (76.9%) nonselective and 4,179 (23.1%) selective antimuscarinic incident users. The unadjusted falls/fractures rate was 27.14% (3,772) for nonselective and 24.55% (1,026) for selective users (p-value< 0.01). The unadjusted all-cause hospitalizations rate was 24.14% (3,354) for nonselective and 21.58% (902) for selective users (p-value <0.01). The IPTW models did not find a significant difference in the risk of falls/fractures (Hazard Ratio [HR] 1.03; 95% Confidence Interval [CI] 0.99-1.07) and risk of all-cause hospitalizations (HR 1.04; 95% CI 0.99-1.08) between nonselective and selective antimuscarinics. Several sensitivity analyses corroborated the main findings.
The study did not find a differential risk of falls/fractures and all-cause hospitalizations in older adults with dementia and OAB using nonselective and selective antimuscarinics. More research is needed to understand the role of pharmacodynamics and pharmacokinetics in the safety profile of antimuscarinics in dementia.
不同的毒蕈碱受体选择性可能导致选择性抗毒蕈碱药物相对于不良反应具有非选择性药物的优势。本研究旨在比较使用非选择性和选择性抗毒蕈碱药物治疗老年痴呆和膀胱过度活动症（OAB）患者发生跌倒/骨折和全因住院的风险。
方法/设计：本研究为回顾性队列研究，纳入了使用抗毒蕈碱药物治疗的老年痴呆和 OAB 患者。主要暴露因素分为非选择性（奥昔布宁、托特罗定、曲司氯铵和非索罗定）和选择性（索利那新和达非那新）。使用逆概率治疗加权（IPTW）的 Cox 比例风险回归评估了非选择性和选择性抗毒蕈碱药物使用后 6 个月内发生跌倒/骨折和全因住院的风险。
本研究队列包括 13896 例（76.9%）非选择性和 4179 例（23.1%）选择性抗毒蕈碱药物新使用者。未经调整的跌倒/骨折发生率为非选择性药物组 27.14%（3772 例），选择性药物组为 24.55%（1026 例）（p 值<0.01）。未经调整的全因住院率为非选择性药物组 24.14%（3354 例），选择性药物组为 21.58%（902 例）（p 值<0.01）。IPTW 模型未发现非选择性和选择性抗毒蕈碱药物在跌倒/骨折风险（风险比 [HR] 1.03；95%置信区间 [CI] 0.99-1.07）和全因住院风险（HR 1.04；95% CI 0.99-1.08）方面存在显著差异。几项敏感性分析证实了主要发现。
本研究未发现老年痴呆和 OAB 患者使用非选择性和选择性抗毒蕈碱药物治疗在跌倒/骨折和全因住院方面存在风险差异。需要进一步研究以了解在痴呆症中抗毒蕈碱药物的药效学和药代动力学在安全性方面的作用。
