Treatment of hypertension with indapamide with or without perindopril is beneficial in the elderly: Results from the HYVET study
March 31, 2008 By Alexandra M. Palmer 
ACC 08-Chicago, IL: Results of the HYpertension in the Very Elderly Trial (HYVET) demonstrate a benefit in the antihypertensive treatment of persons at least 80 years old with or without perindopril. The findings were presented by Dr. Nigel S. Beckett at the American College of Cardiology 2008 Scientific Sessions in Chicago and were simultaneously published in the New England Journal of Medicine today.
The goal of this trial was to evaluate the benefits and risks of providing medical care to very elderly individuals presenting with hypertension. The authors hypothesized that treating these patients would reduce the risk of stroke, but that it may also elevate the risk of death.
The HYVET trial was a randomized, double-blind, placebo-controlled, multicenter study which enrolled 4,761 patients at 195 centers in 13 countries in Western and Eastern Europe, China, Australasia and North Africa.
The study consisted of patients who were at least 80 years old and had hypertension documented by a persistent systolic blood pressure of at least 160 mm Hg. Of the 4,761 patients entered in the placebo run-in phase, 3,845 were randomized to 1.5 mg of indapamide (SR or sustained release) [n=1,933] or matching placebo (n=1,912). In addition, 2 mg or 4 mg of perindopril or matching placebo was administered as necessary to reach the target blood pressure of <150/80 mm Hg. The primary endpoint was fatal or non-fatal stroke.
The duration of follow-up was a median of 1.8 years (mean, 2.1 years, minimum of 0 and a maximum of 6.5 years). At 2 years, 25.8%, 23.9% and 49.5% of patients in the active-treatment arm were being administered indapamide alone, indapamide + 2 mg perindopril and indapamide + 4 mg perindopril, respectively, and 14.2%, 13.4% and 71.8% of patients in the placebo group were receiving the equivalent placebos.
At 2 year follow-up, 48% of patients in the active treatment group reached the target blood pressure of < 150/80 mm Hg compared to only 19.9% of patients in the placebo arm. Compared to placebo, indapamide treatment was associated with a 30% reduction (95% CI, -1 to 51, p=0.06) in the pre-specified primary endpoint of fatal and nonfatal stroke. Secondary endpoints included death from stroke (39% reduction; 95% CI, 1-62, p=0.05), death from cardiovascular causes (23% reduction; 95% CI, -1 to 40, p=0.06), and death from any cause (21% reduction; 95% CI, 4-35, p=0.02). In addition, there was a 64% (95% CI, 42-78, p<0.001) and 34% (95% CI, 18-47, p<0.001) reduction in the rate of fatal or nonfatal heart failure and the rate of any cardiovascular event (myocardial infarction, heart failure and death from cardiovascular causes or stroke), respectively. There were fewer side effects in the active treatment group (p=0.001).
This demonstrates that the use of indapamide with or without perindopril is beneficial among elderly patients with hypertension. In addition, the data indicate a direct relationship between blood-pressure reduction and mortality in elderly patients, a conclusion that makes this trial unique. Contrary to the predicted outcomes, treating very elderly patients with high blood pressure actually lowered the risk of death from any cause. This data however cannot be applied to frail individuals as the study consisted of healthier-than-normal cohorts. Evidence to support diagnosis of a stroke was required by the end-point committee, but it was not always readily available. This was especially the case in patients who died at home without any medical care, since they were not monitored during the last hours of life and since autopsies were not performed.
The aforementioned results provide very useful information pertaining to an important population group in which hypertension is common. The outcome suggests the number of cardiovascular deaths associated with hypertension might be reduced with this treatment regimen.
HYVET was supported by the British Heart Foundation and the Institut de Recherches Internationales Servier.
- Nigel S. Beckett, Ruth Peters, Astrid Fletcher, Christopher Bulpitt, HYVET Committees and Investigators. The Hypertension in the Very Elderly Trial (HYVET): Main Results. As presented at ACC 2008.