(C06) The risk of incident dementia and Alzheimer’s disease after the use of centrally-acting versus non-centrally acting angiotensin-converting enzyme inhibitors: a target trial emulation study
Student The University of Hong Kong Hong Kong, Hong Kong
Background: The angiotensin-converting enzyme inhibitors (ACEi), an antihypertensive drug class, may affect the risk of dementia and Alzheimer’s Disease (AD). It is uncertain whether there is a difference between ACEi that enter the brain (centrally acting) and those that do not (non-centrally acting).
Objectives: This study compares the incidence of dementia and AD between centrally-acting and non-centrally-acting ACEi use.
Methods: Using public healthcare system electronic health records from 2005 to 2020 in Hong Kong, we emulated the randomised trial's design and Intention-to-treat (ITT) analysis. The participants aged 40 years or older who were eligible for ACEIs prescription without previous dementia were included. Individuals were followed up from the initiation of centrally acting ACEi or non-centrally acting ACEi till death, study end date, or the first diagnosis of all-cause dementia and AD. Propensity scores were calculated based on age, sex, comorbidities and drug use history with logistic regression. Cox proportional hazard models with inverse propensity treatment weighting were implemented to estimate adjusted hazard ratios (HR). This study is supported by the Hong Kong Research Grants Council General Research Fund, No. 17113720.
Results: The study included 246,732 new users of ACEIs, with 224,803 (91.1%) centrally-acting and 21,929 (8.9%) non-centrally-acting users. The median age was 62 and 63 years at drug initiation, respectively, with a median follow-up of around 7.5 years. The ITT hazard ratio (95% confidence intervals) of all-cause dementia and AD for centrally-acting ACEi verse non-centrally acting users for the first two years are 0.97 (0.92-1.02) and 0.80 (0.70-0.91), and 0.98 (0.93-1.04) and 0.81 (0.71-0.94) for the entire follow-up.
Conclusions: A 19% AD risk reduction was observed for the participants with centrally-acting ACEi compared to non-centrally acting ACEi, but no difference was observed in the risk of all-cause dementia. Further studies should be conducted in other countries to validate the finding.
