ArticlesRandomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension*
Introduction
The prevalence of isolated systolic hypertension increases with age. Among people aged 70 and older the prevalence is 8%, and it rises to to more than 25% among those aged 80 years or older.1 In 1989, the European Working Party on High Blood Pressure in the Elderly started a placebocontrolled double-blind trial–Systolic Hypertension in Europe (Syst-Eur).2 Active treatment was started with the calcium-channel blocker nitrendipine,3 with the possible addition of enalapril, hydrochlorothiazide, or both. In 1991, the Systolic Hypertension in the Elderly (SHEP) trial showed that diuretic-based treatment prevented stroke, myocardial infarction, and congestive heart failure.4 Because of the remaining uncertainties about the treatment of isolated systolic hypertension in the elderly,5, 6, 7, 8, 9 the Syst-Eur trial continued after the SHEP results were published.4 Furthermore, controversy about calcium-channel blockers as first-line antihypertensive agents10, 11, 12, 13 highlighted the lack of evidence that these drugs reduce cardiovascular risk.
We report the morbidity and mortality results of the Syst-Eur trial. We stopped the trial on Feb 14, 1997, after the second interim analysis because we had reached the primary endpoint of a significant benefit for stroke.2
Section snippets
Methods
The protocol of this trial2 was approved by the ethics committees of the University of Leuven and the participating centres. We used the principles outlined in the Helsinki declaration.14
Patients were recruited from 198 centres in 23 countries across western and eastern Europe. Each centre kept a register of screened patients. Eligible patients were at least 60 years old. On masked placebo during the run-in phase, their sitting systolic blood pressure ranged from 160 mm Hg to 219 mm Hg, their
Results
Of 8926 screened patients 6403 (71·7%) were eligible for enrolment in the run-in period (figure 2). 1708 patients were not included because of blood pressure values outside the recruitment range (n=910 [53·4%]), withdrawal of consent (n=439 [25·7%]), the presence or occurrence of cardiovascular or non-cardiovascular illnesses, prohibiting randomisation (n=202 [11·8%]), symptoms or treatment with masked placebo (n=55 [3·2%]), on for undocumented reasons (n=333 [19·5%]). 1262 (26·9%) of
Discussion
The antihypertensive drugs used in our trial were the dihydropyridine calcium-channel blocker nitrendipine, the converting-enzyme inhibitor enalapril, and the thiazide diuretic hydrochlorothiazide. Among elderly patients with isolated systolic hypertension, these drugs reduced the risk of stroke and the occurrence of various other cardiovascular complications. We saw the benefit of active treatment soon after randomisation, when most patients were still on monotherapy with nitrendipine.
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Investigators listed at end of paper