Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta-analysis

Background/rationale: Long-term treatment with anticholinergic agents may increase the risk of cognitive impairment or dementia. This systematic literature review and meta-analysis aimed to assess the impact of ≥3 months of exposure to anticholinergics as a class on the risk of dementia, mild cognitive impairment, and change in cognitive function. The impact of anticholinergic agents specifically used to treat overactive bladder was also evaluated. Materials and Methods: A systematic literature review was conducted to identify English language articles evaluating the impact of anticholinergic use for ≥3 months on dementia or cognitive function in adult patients. Databases searched included PubMed, Embase, and the Cochrane Library. Meta-analyses were conducted using random-effects models; 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were reported. Results: A total of 2122 records were identified. Out of those, 21 studies underwent qualitative synthesis and 6 reported endpoints relevant for inclusion in a meta-analysis assessing the risk of incident dementia. The overall rate ratio for incident dementia was 1.46 (95% CI: 1.17–1.81; 95% PI: 0.70–3.04; n = 6). The risk of incident dementia increased with increasing exposure (n = 3). In addition, two studies from the meta-analysis reported an increased risk of dementia with ≥3 months of use of bladder antimuscarinics (adjusted odds ratios ranged from 1.21 to 1.65, depending on exposure category). Conclusion: Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics

Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)

Aims: TECOS, a cardiovascular safety trial (ClinicalTrials.gov identifier: NCT00790205) involving 14 671 patients with type 2 diabetes and cardiovascular disease, demonstrated that sitagliptin was non-inferior to placebo for the primary composite cardiovascular outcome when added to best usual care. This study tested hypotheses that medical resource use and costs differed between these 2 treatment strategies. Materials and methods: Information concerning medical resource use was collected on case report forms throughout the trial and was valued using US costs for: Medicare payments for hospitalizations, medical procedures and outpatient visits, and wholesale acquisition costs (WAC) for diabetes-related medications. Hierarchical generalized linear models were used to compare resource use and US costs, accounting for variable intercountry practice patterns. Sensitivity analyses included resource valuation using English costs for a UK perspective. Results: There were no significant differences in hospitalizations, inpatient days, medical procedures, or outpatient visits during follow-up (mean and median 3.0 years in both groups). Hospitalization rates appeared to diverge after 2 years, with lower rates among sitagliptin-treated vs placebo patients after 2.5 years (relative rate, 0.90 [95% CI, 0.83-0.97]; P =.01). Mean medical costs, exclusive of study medication, were 11 937 USD in the sitagliptin arm and 12 409 USD in the placebo arm (P =.06). Mean sitagliptin costs based on undiscounted WAC were 9978 USD per patient. Differential UK total costs including study drug costs were smaller (911 GBP), primarily because of lower mean costs for sitagliptin (1072 GBP). Conclusions: Lower hospitalization rates across time with sitagliptin slightly offset sitagliptin treatment costs over 3 years in type 2 diabetes patients at high risk for cardiovascular events