Association between recently raised anticholinergic burden and risk of acute cardiovascular events: nationwide case-case-time-control study

Objective To evaluate the association between recently raised anticholinergic burden and risk of acute cardiovascular events in older adults.

Design Case-case-time-control study (ie, incorporating a case crossover design and a control crossover design consisting of future cases).

Setting Taiwan’s National Health Insurance Research Database.

Participants 317 446 adults aged ≥65 who were admitted to hospital because of an incident acute cardiovascular event between 2011 and 2018. Acute cardiovascular events included myocardial infarction, strokes, arrhythmias, conduction disorders, and cardiovascular death.

Main outcome measures The anticholinergic burden was measured for each participant by adding up the anticholinergic scores for individual drugs using the Anticholinergic Cognitive Burden Scale. Scores were classified into three levels (0 points, 1-2 points, and ≥3 points). For each participant, anticholinergic burden levels during hazard periods (day −1 to −30 before the cardiovascular event) were compared with randomly selected 30 day reference periods (ie, periods between days −61 and −180). Conditional logistic regression determined odds ratios with 95% confidence intervals to evaluate the association between acute cardiovascular events and recently raised anticholinergic burden.

Results The crossover analyses included 248 579 current cases. Participants’ average age on the index date was 78.4 years (standard deviation 0.01), and 53.4% were men. The most frequently prescribed drugs with anticholinergic activity were antihistamines (68.9%), gastrointestinal antispasmodics (40.9%), and diuretics (33.8%). Among patients with varying levels of anticholinergic burden in different periods, more patients carried higher levels of anticholinergic burden during hazard periods than during reference periods. For example, 17 603 current cases had 1-2 points of anticholinergic burden in the hazard period with 0 points in the reference period, while 8507 current cases had 0 points in the hazard period and 1-2 points in the reference period. In the comparison of 1-2 points versus 0 points of anticholinergic burden, the odds ratio was 1.86 (95% confidence interval 1.83 to 1.90) in the case crossover analysis and 1.35 (1.33 to 1.38) in the control crossover analysis, which yielded a case-case-time-control odds ratio of 1.38 (1.34 to 1.42). Similar results were found in the comparison of ≥3 versus 0 points (2.03, 1.98 to 2.09) and ≥3 versus 1-2 points (1.48, 1.44 to 1.52). The findings remained consistent throughout a series of sensitivity analyses (eg, cut-off points for anticholinergic burden categories were redefined and different scales were used to measure anticholinergic burden).

Conclusions An association was found between recently raised anticholinergic burden and increased risk of acute cardiovascular events. Furthermore, a greater increase in anticholinergic burden was associated with a higher risk of acute cardiovascular events.

The authors remotely accessed the data from the data centre of the Ministry of Health and Welfare in Taiwan. Researchers interested in accessing this dataset could submit a formal application to the Taiwan Ministry of Health and Welfare to request access (No 488, Sect. 6, Zhongxiao E Rd, Nangang District, Taipei 115, Taiwan; website: <https://dep.mohw.gov.tw/DOS/cp-2516-59203-113.html>). No additional data available.

Related Keywords

National Cheng Kung University , Tainan Municipality , Taiwan , Germany , Zhongxiao , Kao Hsiung , Nangang , Hualian Xian , Taipei , T Ai Pei , German , Daniel Hsiang , Edward Chia Cheng Lai , Shih Chieh Shao , Wei Ching Huang , Avery Shuei , Swu Jane Lin , Taiwan Ministry Of Health , World Health Organization , Setting Taiwan National Health Insurance Research Database , National Science , National Health Research Institutes Of Taiwan , National Cause Of Death , National Health Insurance , National Health Insurance Research Database , Technology Council Of Taiwan , Ministry Of Health , Taiwan National Health Insurance Research Database , National Cause Of Death Registry , Drug Administration , College Of Medicine , School Of Pharmacy , Taiwan National Health Insurance , Facebook , Twitter , Shuei He Yang , Chieh Shao , Jane Lin , Chia Cheng Lai , Anticholinergic Cognitive Burden , National Cause , Death Registry , Anticholinergic Cognitive Burden Scale , Anticholinergic Drug Scale , German Anticholinergic Burden Scale , Modified Anticholinergic Cognitive Burden Scale , Korean Anticholinergic Activity Scale , Institutional Review Board , Taiwan Ministry , Nangang District , Technology Council , National Health Research Institutes , Taiwan Food , Open Access , Creative Commons Attribution ,