Risk of Mortality Associated with Non-selective Antimuscarinic medications in Older Adults with Dementia: a Retrospective Study

Background Selective antimuscarinics may offer a favorable safety profile over non-selective antimuscarinics for the management of overactive bladder (OAB) in patients with dementia. Objective To test the hypothesis that non-selective antimuscarinics are associated with increased risk of mortality compared to selective antimuscarinics in older adults with dementia and OAB. Design Propensity score-matched retrospective new-user cohort design among Medicare beneficiaries in community settings. Patients Older adults with dementia and OAB with incident antimuscarinic use. Main Measures The primary exposure was antimuscarinic medications classified as non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) agents. All-cause mortality within 180 days of incident antimuscarinic use formed the outcome measure. New users of non-selective and selective antimuscarinics were matched on propensity scores using the Greedy 5 -> 1 matching technique. Cox proportional-hazards model stratified on matched pairs was used to evaluate the risk of mortality associated with the use of non-selective versus selective antimuscarinics in the sample. Key Results The study identified 16,955 (77.6%) non-selective antimuscarinic users and 4893 (22.4%) selective antimuscarinic users. Propensity score matching yielded 4862 patients in each group. The unadjusted mortality rate at 180 days was 2.6% (126) for non-selective and 1.6% (78) for selective antimuscarinic users in the matched cohort (p value < 0.01). The Cox model stratified on matched pairs found 50% higher risk of 180-day mortality with non-selective antimuscarinics as compared to selective ones (hazard ratio (HR) 1.50; 95% confidence interval (CI) 1.04-2.16). The study findings remained consistent across multiple sensitivity analyses. Conclusions Use of non-selective antimuscarinics was associated with a 50% increase in mortality risk among older adults with dementia and OAB. Given the safety concerns regarding non-selective antimuscarinic agents, there is a significant need to optimize their use in the management of OAB for older patients with dementia.