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Antihypertensive Treatment for the Very Old Found Safe and Effective

ARTICLE IN BRIEF

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Treatment with an older diuretic — with or without an ACE (angiotensiin-converting-enzyme) inhibitor — significantly reduced all-cause mortality, fatal stroke, and heart failure in people, aged 80 and over. Treatment also had favorable effects on non-fatal stroke and cardiovascular mortality.

CHICAGO—Some neurologists believe that antihypertensive treatment in “very old” people (age 80 and older) raises the risk of stroke. A large, randomized trial reported at the annual meeting of the American College of Cardiology here in April suggests that that concern is misguided, and in fact, argues for drug treatment of elderly people with hypertension.

The HYVET (Hypertension the Very Elderly) trial showed that drug treatment with an older diuretic — with or without an ACE (angiotensiin-converting-enzyme) inhibitor — significantly reduced all-cause mortality, fatal stroke, and heart failure. Treatment also had favorable effects on non-fatal stroke and cardiovascular mortality. Moreover, actively treated patients reported fewer serious adverse events than those in the placebo group.

“The HYVET trial study shows that it is never too late to start antihypertensive therapy. This trial expands the upper age limit for treatment and also a decrease in stroke mortality or total mortality. The benefits are seen early and the treatment regimen is safe,” said lead author Nigel S. Beckett, MBChB, of Imperial College in London, UK, who described these results at a late-breaking trials session. The results were also published on March 31 online in advance of the print publication of The New England Journal of Medicine.

STUDY METHODS, RESULTS

HYVET randomized 3,845 patients — recruited from Europe, China, Australia, and Tunisia — 80 years of age or older who had a sustained blood pressure of 160 mmHg or greater to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. Perindopril (2 or 4 mg), an ACE inhibitor, could be added to achieve the target blood pressure of 150/80 mmHg. Subjects were excluded if they had dementia or if they required nursing home care, so the results should be viewed in the context of a reasonably health elderly study population.

The patients were instructed to stop all antihypertensive treatment and take placebo for a run-in period of two months, during which time they had two blood pressure measurements one month apart. Then they were randomized, if their systolic blood pressure was between 160 and 199 mmHg.

Treatment groups were matched for demographic and clinical measures. Ninety percent were known to be hypertensive but only 65 percent had received antihypertensive treatment.

Benefits of treatment were seen during the first year, Dr. Beckett said. The mean follow-up was 1.8 years. By two years, mean seated blood pressure was reduced by 15/6.1 mmHg in the active treatment group compared with the placebo group. With active treatment, there was a 30 percent reduction in stroke, which did not reach statistical significance (p=0.06). Mortality due to any cause was significantly reduced by 21 percent with treatment (p=0.02); death due to cardiovascular disease was reduced by 23 percent (p=0.06). Heart failure was reduced by 64 percent in the treated group (p<0.001). Dr. Beckett said that 57 percent of all strokes occurring during the trial were fatal, and treatment reduced fatal strokes by 39 percent when compared with placebo (p=0.021).

No significant changes in relevant laboratory measures — serum potassium, serum creatinine, uric acid, glucose — were seen more in treated patients that those taking placebo. Serious adverse events were more frequent in the placebo group: 448 versus 358 in the active treatment group (p=0.001). At two years, the number needed to treat (NNT) to prevent one stroke was 95; NNT to prevent one death was 40.

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DR. PHILIP A. WOLF: “Now we know that not treating the very elderly is wrong. The HYVET study raises the bar for age limit.”

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Benefits of treatment — lowering blood pressure — were observed after one year.

Dr. Beckett said that these results are relevant for the growing numbers of elderly patients in industrialized countries. He pointed out that the threshold of a systolic blood pressure of 150 mmHg is conservative, and it may be that lowering blood pressure even more would have greater benefit.

The formal discussor of this report, C. Venkata Ram, MD, said that newer guidelines for the treatment of hypertension should consider a special category for old and very old patients and define blood pressure goals. Dr. Ram is director of the Texas Blood Pressure Institute in Dallas, TX.

A NEUROLOGIST'S PERSPECTIVE

“I was taught in medical school that it is dangerous to lower blood pressure in the elderly because it could trigger a stroke,” said Philip A. Wolf, MD, professor of neurology at Boston University School of Medicine. “I was at the Princeton Conference attended by stroke experts; an audience member raised his hand and said that it was dangerous to lower blood pressure in the elderly because of concern about inducing stroke, so experts still believe this misconception.” The HYVET trial lays this concern to rest, he added.

“We have known for a long time that the level of blood pressure determines stroke risk and that reducing elevated blood pressure prevents, not precipitates, stroke,” Dr. Wolf noted. “Over the years, a series of trials have been conducted: first in severe hypertension; then in moderate and mild hypertension; in younger patients and then in older patients with isolated systolic hypertension. All of these trials have shown a reduction in events with blood pressure lowering.”

“HYVET is an important trial,” Dr. Wolf emphasized, and he hopes that this news will trickle down and affect community practice. The target blood pressure of 150 mmHg in HYVET is a modest target, and he said that there was no harm or penalty for reducing blood pressure. In fact, when heart failure and stroke are reduced, mortality is reduced as well.

“Now we know that not treating the very elderly is wrong,” he said. “The HYVET study raises the bar for age limit.”

REFERENCE

• Beckett NS, Peter R, Bulpitt CJ, et al., for the HYVET Study Group. Treatment of hypertension in patients 80 years of age or old. N Engl J Med 2008:E-pub 2008 March 31.