Significant Reductions In Mortality Shown Using Blood Pressure-lowering Treatment In Very Elderly

The 3,845 patient Hypertension in the Very Elderly Trial (HYVET), which is coordinated by scientists from Imperial College London, is the largest ever clinical trial to look at the effects of lowering blood pressure solely in those aged 80 and over. Patients were given either a placebo or the diuretic indapamide slow release (SR) 1.5mg, with the addition of the ACE inhibitor perindopril in tablet form once a day.

The research shows that the benefits of treatment include a 21% (p=0.02) reduction in total mortality rate, a 39% (p=0.05) reduction in stroke mortality rate, a 64% (p<0.001) reduction in fatal and non-fatal heart failures and a 34% (p<0.001) reduction in cardiovascular events. The benefits were apparent within the first year of follow-up.

The reduction in overall mortality was a novel and unexpected result. Earlier trials had demonstrated that reducing blood pressure in the under-80s reduces stroke and cardiovascular events. However, previous smaller and inconclusive studies also suggested that whilst lowering blood pressure in those aged 80 or over reduced the number of strokes, it did not reduce, and even possibly increased, total mortality.

In July 2007 the trial was stopped early on the recommendation of an independent data monitoring committee after they observed significant reductions in overall mortality and stroke in those receiving treatment. The final results of the trial showed a significant reduction in stroke mortality rate, but the reduction in all strokes of 30% did not quite reach statistical significance (p=0.06) In those aged 80 and over, up to half of strokes are fatal and the reduction in fatal strokes is an important finding.

Emeritus Professor Christopher Bulpitt, the lead investigator on the study from the Care of the Elderly Group at Imperial College London, said: "Before our study, doctors were unsure about whether very elderly people with high blood pressure could see the same benefits from treatment to lower their blood pressure as those we see in younger people. Our results clearly show that many patients aged 80 and over could benefit greatly from treatment. Populations are living longer and we have growing numbers of people living well into their 80s and beyond, so this is good news. We are very pleased that cardiovascular events were reduced safely with a reduction in total mortality."

The researchers hope that their findings will clear up uncertainty amongst clinicians about the benefits of treating those aged 80 and over for high blood pressure.

Dr Nigel Beckett, the trial co-ordinator from the Care of the Elderly Group at Imperial College London, added: "Many very elderly people with high blood pressure are not being treated for it at the moment, because doctors are unsure about whether or not treatment will help them. We hope that following our study, doctors will be encouraged to treat such patients in accordance with our protocol."

As the trial was stopped early, an extension involving patients receiving active-treatment is now underway to assess the longer term benefits of treatment.

Patients with high blood pressure (defined here as a systolic blood pressure between 160-199 mmHg), from thirteen countries across the world, were randomised for the double-blind, placebo-controlled trial, which began in 2001. The mean age of participants was 83 years and 7 months.

Patients were given either placebo or indapamide slow release (SR) with the addition of perindopril, in tablet form once a day as required, to achieve a target blood pressure of 150/80mmHg. The average follow-up of patients was just over 2 years by which time 20% of the placebo subjects and 48% of those taking medication had achieved the target blood pressure of 150/80 mmHg. In those patients who were followed up for longer, a larger number of patients receiving active treatment achieved the target blood pressure

This research was presented March 31 at the American College of Cardiology in Chicago and published simultaneously in the New England Journal of Medicine.

HYVET was co-ordinated by scientists from Imperial College London, working with colleagues around the world. The main trial was funded by both the British Heart Foundation and by Servier.