Reduced Mortality in Treatment Group Halts BP Trial in Elderly

Lisa Nainggolan

August 07, 2007

August 7, 2007 (London, UK) - The largest ever study to look at the effects of lowering BP in those aged 80 and over--the Hypertension in the Very Elderly Trial (HYVET)--has been halted prematurely due to significant reductions in both stroke and overall mortality in the treatment arm [1].

One of the investigators, Dr Ruth Peters (Imperial College, London), told heartwire that the reductions in stroke and mortality observed "were statistically significant and not trivial." She declined, however, to give specific figures. "We are being really cautious about this." She said the plan is to simultaneously publish the results in a peer-reviewed journal and present them at a major medical meeting, "probably sometime next spring."

The decision to halt the study was taken by the steering committee following a recommendation to that effect from the data safety monitoring board last month. All patients in the study are being brought back to have their treatment reviewed and will have the option of switching to the active-therapy arm. The trial had been slated to end in 2009.

Great news for the over-80s

HYVET was being conducted in a number of countries in Eastern and Western Europe as well as in Tunisia and China and included 3845 patients aged 80 or older. HYVET was undertaken because previous smaller studies had produced inconclusive results with regard to whether blood-pressure lowering was beneficial or not in the very elderly. In some studies, although antihypertensive therapy reduced the risk of stroke, it did not reduce--and in some cases increased--mortality.

The entry criteria for HYVET were a sitting systolic blood pressure of 160 to 199 mm Hg and a diastolic BP of 90 to 109 mm Hg. Peters said that later on in the trial, patients with isolated systolic hypertension were also allowed to participate. Patients were randomized to either placebo or a low-dose diuretic (indapamide 1.5 mg sustained release) and an additional ACE inhibitor (perindopril 2 mg or 4 mg a day) if required.

The primary end point is stroke events (fatal and nonfatal), and secondary outcome measures include total mortality, cardiovascular mortality, cardiac mortality, stroke mortality, and skeletal fracture.

"It was not clear prior to our study whether the over-80s would benefit from blood-pressure-lowering medication in the same way as younger people," says lead investigator Dr Chris Bulpitt (Imperial College, London) in a press release.

"Our results are great news for people in this age group because they suggest that where they have high blood pressure, such treatment can cut their chances of dying as well as [suffering a] stroke," he added.

Dr Franz Messerli (Columbia University, New York), who was not involved with the study, commented to heartwire : "The authors of HYVET are to be congratulated for their exciting results and we look forward to studying them in great detail. The fact that HYVET was stopped prematurely . . . is fascinating and hopefully will convert the very last knuckleheads who still argue that blood-pressure elevation in the elderly is a compensatory phenomenon serving to force blood through sclerotic arteries to the target organ.

"A significant reduction in mortality is exceedingly uncommon in a hypertension study and was not observed in previous elderly studies such as Syst Eur or SHEP," he continued. "Apart from ASCOT, we have to go all the way back to the Veteran Administration Studies to find a significant reduction in mortality in a hypertension study. The reduction in stroke is somewhat less surprising. Indapamide has been documented to be an excellent cerebroprotective agent, as data from the PREVENT and PATS studies make clear. In the PATS study, indapamide reduced the risk of stroke by 49% even in the normotensive population."

Dr Robert J Adams (Medical College of Georgia, Augusta), a stroke neurologist also not involved in the study, told heartwire that this trial "provides new and important evidence on an old and vexing problem.

"There remains confusion and concern about blood-pressure treatment in certain groups thought to be at risk from treatment-induced hypotension," he said. "In the very elderly and in other elderly patients after stroke, the targets for blood pressure remain debated. These new data support a growing body of evidence that lower blood pressure prevents stroke even in those we often felt were too frail to treat aggressively. I await the details of the study with interest to see the full results of this trial."

Adams is a member of the editorial board for Medscape Neurology and Neurosurgery.

  1. Imperial College, London. Trial stops after stroke and mortality significantly reduced by blood-pressure-lowering treatment for those aged 80 and over [press release]. August 7, 2007. Available here .

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