The Syst-Eur Trial (1997)

This trial as well as summaries of other important HTN trials can be found on this website here

The story  for this trial actually started with a pilot trial that was published in 1991 (Amery 1991). In this pilot trial publication, it was noted that the European Working Party on High Pressure in the Elderly (EWPHE)  trial which looked at patients with a minimum age of 60 years and a blood pressure of 160-239/90-199 showed that antihypertensive treatment led to a decrease in cardiovascular mortality. It was also noted that 1988, several trials for antihypertensive drug treatment had been published, but most studies included only young and middle-aged patients. Some trials at this time had recruited older patients, but there was still no strong evidence that antihypertensive treatment in the elderly improved total mortality. It noted that until 1988, all published trials mainly recruited patients mainly on the basis of diastolic blood pressure elevation, but that in industrialized countries and diastolic blood pressure peaks at an age of 50 and then stabilizes or decreases. The investigators for this trial decided to test the hypothesis that drug treatment of isolated systolic hypertension would lead to a reduction in cardiovascular mortality and morbidity.  

As noted, during the onset of this trial, there were still some uncertainties about the benefit for treatment of isolated systolic hypertension in the elderly. There was also some controversy about  calcium channel blockers as first-line agents and evidence was lacking that these agents reduced cardiovascular risk. The trial went on to enroll patients at least 60 years old with isolated systolic HTN. The trial enrolled 4695 patients in 198 medical centers across 23 countries in Western and Eastern Europe. The patients were randomly assigned to active treatment or placebo. Active treatment included a dihydropyridine calcium channel blocker called nitrendipine with the possible addition of enalapril and hydrochlorothiazide.  The trial was stopped early because the trial had reached a primary endpoint of a significant benefit for stroke. At a median of two years of follow-up, it was found that active treatment led to a reduction in the total rate of stroke from 13.7% to 7.9%. Non-fatal stroke, all fatal and nonfatal cardiac in points including sudden death, were decreased significantly in the active treatment group. The information that this study gives us is that among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with a dihydropyridine calcium channel blocker reduces the rate of cardiovascular complications.

Syst-Eur Trial: Staessen, J. A., Fagard, R., Thijs, L., Celis, H., Arabidze, G. G., Birkenhäger, W. H., ... & Forette, F. (1997). Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Lancet, 350(9080), 757-764.

Syst-Eur Trial PMID: 9297994

Useful summaries of the Syst-Eur Trial: cardiologytrials.org

Other References

Amery, A., Birkenhäger, W., Bulpitt, C. J., Clement, D., De Leeuw, P., Dollery, C. T., ... & O’Brien, E. T. (1991). Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization. Aging Clinical and Experimental Research, 3(3), 287-302.