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.