OT: amlodipine deficiency: Normal' Blood Pressure May Still Be Too High - Pfizer study

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http://www.nytimes.com/2004/11/10/health/10heart.html

'Normal' Blood Pressure May Still Be Too High

By GINA KOLATA

Anew study of heart disease patients finds that " normal " blood pressure

may not be low enough. By reducing their pressure well below the levels

suggested by national guidelines, patients had fewer heart attacks,

strokes, cardiac arrests, hospitalizations for chest pain, procedures to

open blocked coronary arteries, and deaths.

In addition, lower blood pressure appeared to slow or stop the growth of

the fatty deposits called plaque in the coronary arteries, compared with

patients taking a placebo, whose plaque growth continued over the

two-year study.

The international study, led by Dr. Nissen of the Cleveland

Clinic, is being published today in The Journal of the American Medical

Association. It found that for every 16 heart disease patients with

normal blood pressure given drugs to lower it, 1 adverse event could be

prevented.

Although the study was modest in size, with 1,991 patients, all with

normal blood pressure, experts said its surprising result reopened this

longstanding question: How low should blood pressure go?

The question takes on special urgency because millions of Americans have

heart disease severe enough to cause the adverse symptoms.

The patients in the study were at high risk for adverse events, Dr.

Nissen said, but their blood pressure was considered so well controlled

that researchers had not previously asked what would occur if it went

lower. Their starting pressure, he said, " was 10 millimeters lower than

anyone has studied. "

Blood pressure is measured in millimeters of mercury. National

guidelines for most people say systolic pressure, when the heart

contracts, should be lower than 140 millimeters. Diastolic pressure,

when the heart relaxes between beats, should be lower than 90. When the

new study began, its participants averaged 129 over 78.

" If you walked in a doctor's office and your blood pressure was 129 over

78, your doctor would say you have normal blood pressure, " Dr. Nissen said.

The research was sponsored by Pfizer, which makes a drug in the study,

amlodipine, or Norvasc. But the investigators say they, not the company,

controlled the data and wrote the paper. While Pfizer saw the manuscript

before it was submitted for publication, they wrote, " the final decision

on content was exclusively retained by the authors. "

The investigators and other experts said more research was needed before

changing the national guidelines. Still, they said, the new study should

advance the discussion.

" It's a brick in the wall that is being built in terms of ever lower

targets for blood pressure, " said Dr. Cutler, a blood pressure

researcher at the National Heart, Lung and Blood Institute.

The findings do not apply to healthy people, for whom the side effects

of blood pressure drugs may outweigh any benefits of taking them.

Amlodipine, for example, can cause swollen ankles, and enalapril a dry

cough.

" You really can't generalize to people without pre-existing disease, "

said Dr. K. Whelton, senior vice president for health sciences at

Tulane University.

The study began with a question, said one investigator, Dr. Libby

of the Harvard Medical School: " Is average blood pressure optimal for

our species? "

Most studies have focused on reducing high blood pressure to average

levels. Such reductions seem to reduce the risk of heart attacks and

strokes.

In the new study, patients with average blood pressures were randomly

assigned to take one of two types of drugs to lower their pressure

further - Pfizer's drug amlodipine, from a class known as calcium

channel blockers, or enalapril, a generic drug in the class ACE

inhibitors - or to take a placebo.

The two drugs had similar effects on blood pressure, reducing systolic

pressure an average of 5 points and diastolic by an average of 3. The

number of cardiac events like heart attacks, strokes or hospitalizations

for chest pains was reduced 31 percent for patients taking amlodipine

and 15 percent for those taking enalapril. Amlodipine also stops plaque

growth in coronary arteries.

Among the placebo group, 23 percent, or 151 patients, had such an event

during the two-year study. But for those taking amlodipine, the figure

was 16.6 percent, or 110. For those on enalapril, it was 20.2 percent,

or 136.

Some experts not connected with the study said that they were not sure

that amlodipine was better, that study was too small to be definitive.

" To me, that suggests that the major benefit is blood pressure lowering,

no matter how you get there, " said Dr. Carl J. Pepine, chief of the

cardiovascular medicine division at the University of Florida.

Dr. P. Giles, a professor of medicine at Louisiana State

University School of Medicine who is the president of the American

Society of Hypertension, said the figures were encouraging for heart

disease patients. The study " shows you can stop progress of

atherosclerosis and have some regression and you can accomplish that

with a reduction of a blood pressure level that some people have

considered normal, " he said.

The findings also are consistent with studies of populations that

indicate that the risk of heart attacks increases continuously as

diastolic pressure climbs above 115, Dr. Giles and other researchers said.

Virtually all experts not employed by the government have been paid

consultants for drug companies.

" We have taken it as the natural human condition that blood pressures

are as high as they are, " said Dr. Henry R. Black, an associate vice

president for research at the Rush University Medical Center and an

author of the blood pressure guidelines. " We have arbitrarily defined

'normal blood pressure.' " But that, Dr. Black said, does not mean that

normal is optimal.

Dr. Libby, for one, was astonished by the findings. " It was an

eye-opener, " he said.

It means, he added, that " we have to rethink blood pressure levels for

those with heart disease. "

*

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