Early ReportPrevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial
Introduction
In 1997 the Rotterdam Study showed that indicators of atherosclerosis, such as hypertension, were associated not only with vascular dementia, but also with Alzheimer's disease.1 Although hypertension is the strongest risk factor for vascular dementia2 the placebo-controlled Systolic Hypertension in the Elderly Program (SHEP) study3 did not confirm the hypothesis that antihypertensive treatment, with chlortalidone, would reduce the incidence of dementia.
As part of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial,4, 5 the vascular dementia project aimed to investigate whether antihypertensive treatment starting with the calcium-channel blocker nitrendipine could prevent vascular dementia in older patients with isolated systolic hypertension. The Syst-Eur trial stopped on Feb 14, 1997, according to predefined stopping rules,5 because the second of four planned interim analyses had shown a significant benefit for stroke, the primary endpoint.4
Section snippets
General design
The protocol of the Syst-Eur trial, described elsewhere,4, 5 was approved by the ethics committee of all participating centres. Eligible patients had to have no dementia, be at least 60 years old, and have a systolic blood pressure when seated of 160–219 mm hg with diastolic blood pressure below 95 mm hg.
After stratification by centre, sex, and previous cardiovascular complications, the patients were randomly assigned double-blind treatment with active medication or placebo by means of a
Results
At 106 centres in 19 European countries 3162 patients were enrolled. However, owing to the early termination of the trial (figure 1), 692 patients did not accumulate 1 year of follow-up and their cognitive function was therefore not taken into account in this assessment (figure 2). In addition, 52 patients were excluded (figure 2). Thus, the number of patients for the present analysis totalled 2418. At randomisation, the patients allocated placebo (n=1180) and those allocated active treatment
Discussion
In elderly patients with isolated systolic hypertension, active treatment starting with the dihydropyridine calcium-channel blocker nitrendipine halved the rate of dementia from 7·7 to 3·8 cases per 1000 patient-years. Selective recruitment of relatively healthy patients who would accept long-term follow-up in a double-blind trial is likely to explain the high MMSE scores (median 29 points) at entry and the low incidence of dementia in the placebo group (7·7 per 1000 patient-years), compared
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