Associations between falls and other serious adverse events and antihypertensive medication in individuals with dementia: An observational cohort study

Background The balance of benefits and risks associated with lowering blood pressure levels in individuals with dementia remains controversial with a lack of evidence for possible harms associated with antihypertensive treatment. We examined the association between antihypertensive medication and serious adverse events in individuals with dementia compared to those without dementia. Methods and findings This was a retrospective analysis using nationally representative UK general practice population between 1998 and 2018, from electronic health records (Clinical Practice Research Datalink, CPRD, GOLD). Eligible individuals were aged ≥40 years, with a systolic blood pressure 130–179 mmHg, and not previously prescribed antihypertensive treatment. The diagnosis of dementia was based on clinical codes in the electronic health record. Individuals were allocated to the exposure group if they were prescribed at least one antihypertensive medication during a 12-month exposure period. Those who were not prescribed any antihypertensive medication during the exposure period were allocated to the control group. The primary outcome was the first hospitalisation or death from a fall within 10 years of the follow-up period. Secondary outcomes were first hospitalisation or death from hypotension, syncope, and fracture. In a population of 1,219,732 individuals, 23,510 had dementia. Antihypertensive medications were newly prescribed in 4,062/23,510 (17.3%) individuals with dementia and 142,385/1,196,222 (11.9%) individuals without dementia in the 12-month exposure period. In the primary analyses, which adjusted for the propensity score and a previous history of the outcome of interest, antihypertensive treatments were associated with a small increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.08, 1.22), hypotension (aHR 1.51, 95%CI 1.29, 1.78), syncope (aHR 1.34, 95%CI 1.11, 1.61), but not fracture (aHR 1.05, 95%CI 0.96, 1.15), in individuals with dementia. These findings were consistent across different analytic approaches, including multivariable adjustment, propensity score matching, and inverse probability treatment weighting. In individuals without dementia, the association between antihypertensive treatment and serious adverse events was similar, with a small increased risk of hospitalisation or death from falls (aHR 1.07, 95%CI 1.05, 1.10). However, the absolute fall risk associated with antihypertensive treatment was significantly higher in individuals with dementia (47 per 10,000 individuals per year, 95%CI 26, 70) compared to those without (14 per 10,000 individuals per year, 95%CI 10, 18). The absolute risks of hypotension and syncope with antihypertensive treatment were also higher in the individuals with dementia compared to those without. The main limitation is the possibility of unmeasured confounding, and heterogeneity in dementia diagnoses based on coded entries in the electronic health record. Conclusions Antihypertensive treatment was associated with increased risk of serious adverse events in individuals with and without dementia, however, the absolute risk of harm was more than double in individuals with dementia. These data suggest that clinicians, patients, and their carers should consider these risks before starting new antihypertensive medications, particularly in the context of dementia.