Hypertension in the Very Elderly Trial - HYVET


The goal of this trial was to evaluate the risk–benefit ratio of indapamide in the treatment of hypertensive geriatric patients (ages >80 years) compared with placebo.


Indapamide is beneficial in reducing the incidence of adverse clinical outcomes in patients over the age of 80 years, and with systolic blood pressure between 160 and 199 mm Hg, with a good safety profile.

Study Design

Patients Screened: 4,761
Patients Enrolled: 3,845
Mean Follow Up: 1.8 years
Mean Patient Age: 84 years
Female: 61

Patient Populations:

• Age >80 years
• Baseline systolic blood pressure between 160 and 199 mm Hg
• Diastolic blood pressure <110 mm Hg


• Standing systolic blood pressure <140 mm Hg
• Stroke in the last 6 months
• Dementia
• Need for daily nursing care

Primary Endpoints:

All strokes (fatal and nonfatal)

Secondary Endpoints:

• All-cause mortality
• Cardiovascular mortality
• Cardiac mortality
• Death from stroke
• Heart failure

Drug/Procedures Used:

After initial screening, patients with hypertension were randomized to either indapamide SR 1.5 mg or to placebo. Perindopril 2-4 mg could be added on during follow-up to achieve target blood pressure of 150/80 mm Hg.

Concomitant Medications:


Principal Findings:

A total of 3,845 patients were randomized: 1,933 to the indapamide arm and 1,912 to the placebo arm. The mean age at baseline was 83.6 years and the mean entry blood pressure was 173/91 ± 9/8 mm Hg. About 32.5% of patients had isolated systolic hypertension, whereas 89.9% had known hypertension. The incidence of prior stroke was 6.8%.

The study was terminated early, when the second planned interim analysis showed a significant reduction in the incidence of strokes, as well as total mortality in the indapamide arm. At the end of the trial, 1,882 patients were still undergoing double-blind follow-up.

Over a median follow-up of 1.8 months, there was a significant reduction in both the systolic (15 mm Hg) and diastolic (6 mm Hg) blood pressure in the treatment arm compared with the placebo arm. Compared with the placebo arm, there was a 30% reduction in the incidence of the primary outcome of stroke (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-1.01; p = 0.055), a 21% reduction in total mortality (HR 0.79, 95% CI 0.65-0.95; p = 0.05), a 39% reduction in fatal strokes (HR 0.61, 95% CI 0.38-0.99; p = 0.046), and a 64% reduction in heart failure (HR 0.36, 95% CI 0.22-0.58; p < 0.001) in the treatment arm. Similar results were obtained on the per-protocol analysis.

There was no significant difference between the two arms in the levels of potassium, uric acid, glucose, or creatinine. Serious side effects were more common in the placebo arm (23.4%) compared with the treatment arm (18.5%) (p = 0.001). The number needed to treat at 2 years was 94 for stroke and 40 for mortality.


The results show that there is significant benefit obtained with the treatment of hypertension in patients older than 80 years with hypertension. Treatment with indapamide reduces the incidence of strokes, mortality, and congestive heart failure in these patients. These benefits were noted early, with few significant side effects.

This is a landmark study, which challenges current paradigms that question the risk–benefit of treating hypertension in patients older than 80 years of age. Earlier epidemiologic studies had suggested that there was a potential for harm in patients over the age of 80 years who received antihypertensive treatment and had systolic blood pressure <140 mm Hg. Also, randomized clinical trials on the treatment of hypertension in the elderly have either been too small or have excluded patients older than 80 years of age.

Newer guidelines will need to consider this population specifically, with defined blood pressure goals. Although indapamide is different compared with hydrochlorothiazide, they both have similar mechanisms of action, and so treatment with hydrochlorothiazide should be an effective initial treatment regimen in these patients.


Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-1898.

The Hypertension in the Very Elderly Trial (HYVET): Main Results. Presented by Dr. Nigel Beckett at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Statins, Acute Heart Failure, Hypertension

Keywords: Perindopril, Stroke, Follow-Up Studies, Diuretics, Creatinine, Uric Acid, Potassium, Heart Failure, Indapamide, Hydrochlorothiazide, Confidence Intervals, Hypertension

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