Long-term risk of dementia with angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors in hypertensive patients: A 15-year follow-up using the 45 and Up Study

Abstract

It is still unclear whether hypertensive patients using angiotensin II receptor blockers (ARBs) have a different risk of developing dementia compared with those taking angiotensin-converting enzyme inhibitors (ACEIs). We conducted a prospective cohort study using the 45 and Up Study Cohort in patients aged ≥ 45 years with hypertension who initiated ARB or ACEI therapy between 2004 and June 30, 2022. ARB/ACEI exposure was defined as having a supply that covered at least 80% of their follow-up period. Propensity score matching was used to balance baseline characteristics. We used the Cox proportional hazards model to estimate the risk of incident dementia. We included 51,574 patients with hypertension (mean age 66.3 (9.0) years; 48.2% women), with a mean follow-up of 11.3 (5.2) years. After controlling for major modifiable lifestyle factors such as diet and physical activity, ARB use was linked to a significantly reduced risk of dementia compared with ACEI use (hazard ratio [HR] = 0.72; 95% confidence interval [CI]: 0.65-0.80, p < 0.001). In exploratory agent-level analyses, compared with lisinopril, olmesartan (HR = 0.32; 95% CI: 0.16-0.62), candesartan (HR = 0.41; 95% CI: 0.24-0.69), telmisartan (HR = 0.42; 95% CI: 0.25-0.71), irbesartan (HR = 0.45; 95% CI: 0.27-0.75), and perindopril (HR = 0.52; 95% CI: 0.31-0.87) were associated with a significantly lower risk of dementia, while captopril showed a significantly increased risk (HR = 4.9; 95% CI: 1.04-23.4). The findings were consistent across subgroup analyses (sex, head-to-head ARBs vs ACEIs) and sensitivity analyses (excluding hypertension defined only by antihypertensive medication use, adjusting for competing risk of death or inverse probability of treatment weighting analysis). Among hypertensive patients, ARB use was linked to a reduced risk of dementia compared with ACEI treatment, regardless of diet and physical activity, and the effect varied across specific agents. These findings highlight the potential role of ARBs in dementia prevention; however, further randomised controlled trials are needed to confirm them.