Antimuscarinic medication used for the treatment of overactive bladder in women and the risk of cognitive decline, cardiovascular disease and mortality—a systematic review

BACKGROUND: Overactive bladder is common among older women and often managed with antimuscarinic agents. These medications contribute to cumulative anticholinergic burden, which has been associated with adverse outcomes including cognitive decline, cardiovascular morbidity and mortality. This study aimed to evaluate the association between bladder antimuscarinics and these outcomes in adult women. METHODS: A systematic review and meta-analysis were conducted following PROSPERO registration. Six databases were searched up to 15 January 2025. Eligible studies included adult women (≥18 years, >50% female sample) exposed to antimuscarinics, compared to placebo or non-use and reported outcomes of cognitive decline, cardiovascular disease or mortality. Randomised controlled trials (RCTs), observational cohort studies and case-control studies were included. Data were synthesised using a random effects model. RESULTS: Thirty-seven studies met inclusion criteria, all in older populations. Meta-analysis of eight RCTs (n = 675 participants) found no significant cognitive effects at mean follow-up of 19.5 days [standardised mean difference -0.23; 95% confidence interval (CI) -0.61 to 0.15, I2 75%]. Ten cohort studies indicated increased risk of cognitive decline or dementia at mean follow-up of 7.5 years, with a pooled odds ratio (OR) of 1.33 (95% CI 1.10-1.61) and a hazard ratio (HR) of 1.24 (95% CI 1.19-1.30). Two studies reported increased cardiovascular risk (OR 1.13; 95% CI 1.01-1.25) and three studies reported increased mortality (OR 1.26; 95% CI 1.17-1.36). All studies demonstrated concerns regarding risk of bias. CONCLUSION: Bladder antimuscarinics may increase long-term risks of dementia, cardiovascular events and mortality in older women. While RCTs do not suggest direct cognitive harm, caution is advised. These findings are constrained by the low quality of the underlying evidence.