Abstract
Background:
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) are first-line antihypertensive drugs for many patients, and influencing angiotensin systems may play a role in dementia risk. This study aimed to investigate whether exposure to different antihypertensive drug classes compared with ACEI affects the risk of dementia and pathological dementia subtypes in a large multinational database study.
Methods:
This was a multinational population-based cohort study using electronic health databases in Hong Kong, the UK, Sweden and Australia. A common protocol was used to harmonise the study design. An active comparator, a new user design, was applied to compare the risk of all-cause dementia between different antihypertensive drug classes, with secondary outcomes of Alzheimer’s disease (AD) and vascular dementia (VaD). Adjusted Cox proportional hazards models with inverse probability of treatment weighting were used to generate results in each study site and were pooled in meta-analysis.
Results:
One million nine hundred twenty-five thousand, five hundred sixty-three individuals were included across the four databases with a median follow-up ranging from 5.6 to 8.4 years. Compared to ACEI, initiation with ARB was associated with a reduced risk of incident all-cause dementia [hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.89–0.94] and VaD (HR 0.87, 95% CI 0.78–0.96) but not AD.
Conclusions:
This is the largest multinational cohort study conducted to date investigating different classes of antihypertensive drugs and the risk of incident dementia. When initiating antihypertensives, physicians and patients should consider the reduced risk of all-cause dementia and VaD with ARB compared with ACEI in their risk–benefit assessment.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) are first-line antihypertensive drugs for many patients, and influencing angiotensin systems may play a role in dementia risk. This study aimed to investigate whether exposure to different antihypertensive drug classes compared with ACEI affects the risk of dementia and pathological dementia subtypes in a large multinational database study.
Methods:
This was a multinational population-based cohort study using electronic health databases in Hong Kong, the UK, Sweden and Australia. A common protocol was used to harmonise the study design. An active comparator, a new user design, was applied to compare the risk of all-cause dementia between different antihypertensive drug classes, with secondary outcomes of Alzheimer’s disease (AD) and vascular dementia (VaD). Adjusted Cox proportional hazards models with inverse probability of treatment weighting were used to generate results in each study site and were pooled in meta-analysis.
Results:
One million nine hundred twenty-five thousand, five hundred sixty-three individuals were included across the four databases with a median follow-up ranging from 5.6 to 8.4 years. Compared to ACEI, initiation with ARB was associated with a reduced risk of incident all-cause dementia [hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.89–0.94] and VaD (HR 0.87, 95% CI 0.78–0.96) but not AD.
Conclusions:
This is the largest multinational cohort study conducted to date investigating different classes of antihypertensive drugs and the risk of incident dementia. When initiating antihypertensives, physicians and patients should consider the reduced risk of all-cause dementia and VaD with ARB compared with ACEI in their risk–benefit assessment.
| Original language | English |
|---|---|
| Article number | afaf121 |
| Number of pages | 13 |
| Journal | Age and Ageing |
| Volume | 54 |
| Issue number | 5 |
| Early online date | 25 May 2025 |
| DOIs | |
| Publication status | Published - May 2025 |
Bibliographical note
Copyright © The Author(s) 2025. Published by Oxford University Press on behalf of the British Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]Funding
This study was supported by the Hong Kong Research Grants Council General Research Fund, No. 17113720. The study sponsor was not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
| Funders | Funder number |
|---|---|
| Hong Kong Research Grants Council General Research Fund | 17113720 |
Keywords
- Aged
- Aged, 80 and over
- Angiotensin Receptor Antagonists/therapeutic use
- Angiotensin-Converting Enzyme Inhibitors/therapeutic use
- Antihypertensive Agents/therapeutic use
- Australia/epidemiology
- Databases, Factual
- Dementia/epidemiology
- Female
- Hong Kong/epidemiology
- Humans
- Hypertension/drug therapy
- Incidence
- Male
- Middle Aged
- Risk Assessment
- Risk Factors
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