Discontinuation of antihypertensives may not improve cognitive function in elderly [DANTE study]

1. In the elderly with mild cognitive deficits, discontinuing their antihypertensive treatment did not improve their cognitive, psychological or daily functioning at 16-week follow-up.

2. Quality of life did not significantly differ between those who had their antihypertensive medications stopped and those who did not.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The effect of medications on the body differs as one ages. Hypertension predisposes patients to the risk of cognitive decline, due to cerebrovascular disease. However, observational studies indicate that as age increases, this relationship may reverse, as lower blood pressures increase the risk of cognitive decline. This may be due to altered cerebrovascular autoregulation in the elderly. However, this relationship has not been studied in a controlled environment. The objective of this randomized controlled trial was to assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive decline would improve cognitive, psychological and general daily functioning.

Discontinuation of antihypertensive medications in elderly people with mild cognitive decline did not improve cognitive, psychological or daily functioning as compared to those whose medications were not stopped. Adverse outcomes, such as myocardial infarctions, death, transient ischemic attacks, strokes, did not differ significantly between the two groups. Strengths of this study include using multiple, validated scoring systems to determine cognitive functioning. However, a major limitation included the lack of blinding to the intervention, as no placebo was used. Also, although this was a negative trial, it would be important to have increased follow-up to assess if ceasing antihypertensives resulted in increased mortality, cardiovascular or cerebrovascular events.

Click to read the study, published today in JAMA Internal Medicine

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In-Depth [randomized controlled trial]: This community-based, single-blinded, non-placebo, randomized controlled trial took place in the Netherlands (NLD) from June 2011 to August 2013. It included patients from 128 general practices across NLD who were 75 and older with mild cognitive deficits (MMSE score of 21-27), without serious cardiovascular disease and on antihypertensives. Patients were randomized to either have their antihypertensive discontinued or continued. The overall change in cognition compound score was analyzed using validated scoring scales. Intention-to-treat analysis was performed from January to April 2014.

A total of 385 patients were randomized to the exposure groups, 199 to discontinuation of antihypertensives and 186 to continuation of antihypertensives. As expected, there was a significant increase in blood pressure in the discontinuation group as compared to those who remained on their antihypertensive: SBP difference 7.36 mmHg (95%CI 3.02-11.69, p = 0.001) and DBP difference 2.63 mmHg (95%CI 0.34-4.93, p = 0.03). However, there was no significant difference in overall cognition score between the two intervention groups, differences being 0.02 (95%CI -0.19 to 0.23, p = 0.84). There was also no significant difference in the secondary outcomes of psychological or daily functioning. Serious adverse events were also equally distributed across both intervention groups.

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