New results from the Hypertension in the Very Elderly Trial (HYVET) suggest that reducing blood pressure might reduce the risk of dementia in those aged 80 and over, according to research published early Online today (Tuesday 8 July 2008) and in the August issue of Lancet Neurology.
The HYVET-COG (the dementia sub-study of HYVET) results build on evidence from previous research. When combined with results from other placebo-controlled trials, they show that antihypertensive treatment leads to a significant (13%) reduction in dementia. Dr Ruth Peters from the Division of Medicine, Imperial College London said: "The results from HYVET-COG suggest a possible additional benefit associated with antihypertensive treatment in addition to the cardiovascular benefits as already demonstrated in this very elderly group."*
Patients with hypertension (systolic blood pressure [SBP] 160-200 mm Hg; diastolic pressure [DBP] <110 mm Hg) who were aged 80 years or older were enrolled in this double-blind, placebo-controlled trial. Patients were randomly assigned to receive 1.5mg sustained release indapamide, with the option of an additional 2-4 mg perindopril (both AHT drugs) or placebo. The target SPB was 150mm Hg, and the target DBP 80 mm Hg. Participants had no clinical diagnosis of dementia at the start of the trial, and cognitive function was assessed at the start and then annually with a standard test called the mini-mental state examination (MMSE). Possible cases of dementia, shown by a drop of MMSE to below 24 points or by more than three points in a year, were assessed using standard diagnostic criteria and were subject to expert review. The trial was stopped earlier than planned in 2007, at the second yearly analysis, because treatment showed death and stroke rates had fallen in patients given AHT, and thus it was unethical to continue a trial in which potentially life-saving treatment was not being provided to all patients.
Of the 3336 HYVET participants that had at least one-follow up assessment (mean follow-up 2.2 years), 1687 were allocated to AHT and 1649 to placebo. AHT decreased SBP by an extra 15.0 mm Hg and DBP by an extra 5.9 mm Hg compared with placebo. Rates of dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patients-years in the AHT group, but the difference was not statistically significant. However, when the dementia data was combined into a meta-analysis with other placebo-controlled trials of AHT, the combined results showed AHT significantly reduced dementia incidence by 13%.
The authors discuss that the non-significant finding of decreased dementia in HYVET-COG could have been due to short follow-up, the early termination of the trial, or the modest effect of treatment. They conclude: "The HYVET results provide some support for the treatment of very elderly people with hypertension to reduce incident dementia. The meta-analysis of HYVET and three similar trials showed that the reduction in the risk of dementia associated with lowering blood pressure might be clinically significant."
In an accompanying Comment, Dr Ingmar Skoog, Institute of Neurosciences, Sahlgrenska Academy at Göteburg University, Sweden, says: "What are the clinical implications of these findings? The HYVET investigators show that short term antihypertensive treatment is beneficial for stroke and total mortality among the very elderly; therefore detection and treatment of hypertension in elderly people, irrespective of whether it prevents dementia, is important because it might prevent cardiovascular disease."
Notes to editors: *this is a quote direct from the author and cannot be found in the text of the paper
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