The Hypertension in the Very Elderly Trial (HYVET) provided evidence of the benefits of treating very elderly (> 80 years) people with hypertension. Despite the short follow-up (mean 2.1 years), total mortality was found to have been reduced by 21% (p=0.019) and cardiovascular events by 34% (p<0.001). The HYVET Steering Committee agreed that a one year open label extension to run seamlessly from the end of the main trial might provide additional information to that obtained during the main trial, including whether early benefits would be seen in such an elderly group. The main findings from the trial extension have been reported in the BMJ.

Subjects on double blind treatment at the end of the primary study were eligible to enter the extension and 91% (n- 1712 of 1882) agreed to participate. Those on active blood pressure lowering treatment (indapamide SR 1.5 mg [plus perindopril 2 to 4 mg if required]) continued on it, whilst those on placebo were given active treatment. The extension phase aimed for the same target blood pressure of <150/80 mmHg. The primary outcome was all stroke; other outcomes included total mortality, cardiovascular mortality, and cardiovascular events.

During the extension period, 1682 patient years were accrued and the following findings reported:

• By six months, the difference in blood pressure between the two groups was 1.2/0.7mmHg.

• Comparing people previously treated with active drug and those previously on placebo, no significant differences were seen for stroke (n=13; hazard ratio 1.92, 95% CI, 0.59 to 6.22) or cardiovascular events (n=25; 0.78, 0.36 to 1.72).

• Differences were seen for total mortality (47 deaths; hazard ratio 0.48, 0.26 to 0.87; p=0.02) and cardiovascular mortality (11 deaths; 0.19, 0.04 to 0.87; p=0.03).

The researchers conclude from these findings that “very elderly patients with hypertension may gain immediate benefit from treatment. Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment.”

An accompanying Comment article describes HYVET as “one of the most important trials in the history of antihypertensive treatment” and given the steep increase in the number of people living beyond their 80s, the findings have important implications for public health. However it suggests cautious interpretation of the results due to study limitations such as:

1. The number of overall and cause specific events was small, with large confidence intervals around the hazard ratios and there was limited statistical power to discriminate safely between-group differences.

2. The data lacked internal consistency, possibly due to the play of chance.

3. The group originally taking placebo needed active treatment for about six months to achieve blood pressure values similar to group originally on active treatment, thus increasing possibility of blood pressure related events, and making the difference from the early treatment group dependent not on earlier implementation of treatment but on persistence of inadequate blood pressure control in the group originally on placebo.

The authors of the Comment stress that these limitations do not stem from shortcomings in design or conduct of the study, but from the fact that trials in very elderly patients present special difficulties. Nevertheless, they conclude that these data reinforce the conclusion drawn from the earlier results that treatment of hypertensive octogenarians is beneficial and should be pursued.