Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial

Background: Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. Objective: To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. Design: Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. Subjects: Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) <= 160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492). Measurements: Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks. Results: From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. Conclusion: Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.