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

Abstract

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 newuser 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%) nonselective 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.

The Effectiveness in Activating M-Type K+ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action

“…These actions probably result in its perturbations on the functional activities of electrically excitable cells (e.g., GH 3 or mHippoE-14 cells), in the case that in vivo findings occur. Whether the impairment of cognitive function after long-term administration of SOL [20][21][22][23][24][25][26][27][28][29][30][31] could be intimately connected with its stimulation of I K(M) in central neurons remains to be further investigated.…”

“…Evidence has recently accumulated that the treatment with SOL could be linked to an increased risk of the impairment in cognitive functions [20][21][22][23][24][25][26][27][28][29][30][31]. Earlier reports have also reported the ability of this drug to influence the muscarinic activity in cerebral cortex and hippocampus [67,68].…”

“…Findings from the present observations en us to reflect that the IK(M) inherent in different cell types could be an additional and non-canonical target through which SOL can act to govern the functional activities of Earlier clinical investigations have revealed the efficacy and safety of the antimuscarinic, solifenacin (SOL), for treating patients with overactive bladder or neurogenic detrusor overactivity [1][2][3][4][5]7,8,[10][11][12][13][14][15][16][17][18][19]. However, recent evidence has been reported showing that the treatment with SOL could be closely linked to an increased risk of the impairment in cognitive functions [20][21][22][23][24][25][26][27][28][29][30][31]. Therefore, it is pertinent to reappraise the mechanism of SOL actions on electrical behaviors in varying excitable cells, given that its growing clinical use occurs [6,32].…”

Comparative risk of adverse outcomes associated with nonselective and selective antimuscarinic medications in older adults with dementia and overactive bladder

“…Some studies have also associated antimuscarinics use with increased occurrence of falls/fractures 45,46 and hospitalizations, 46,47 , and only one study focused on the differential risk based on the selectivity of antimuscarinics. Our previous study evaluated the comparative risk of all‐cause mortality from nonselective versus selective antimuscarinic use in the same population as in the current study and identified 50% increased risk of up to 180‐day mortality (HR 1.50; 95% CI 1.04–2.16) 48 . Others have specifically focused on the association between individual antimuscarinics and outcomes like falls/fractures or hospitalizations 49,50 .…”

“…[24][25][26] Some studies have also associated antimuscarinics use with increased occurrence of falls/fractures 45,46 and hospitalizations, 46,47, and only one study focused on the differential risk based on the selectivity of antimuscarinics. Our previous study evaluated the comparative risk of all-cause mortality from nonselective versus selective antimuscarinic use in the same population as in the current 48 Others have specifically focused on the association between individual antimuscarinics and outcomes like falls/fractures or hospitalizations. 49,50 Gomes et al, compared oxybutynin versus tolterodine, and reported no difference in the risk of falls, no difference in the risk of fractures, but 12% significant increase in the risk of all-cause hospitalizations (adjusted HR 1.12, 95% CI 1.07-1.17).…”