ASPIRIN HYPE OR HOPE? (2024)

men.

The worry is that Americans will see aspirin as a "quick fix" for

heart disease, overlooking the study's fine print, ignoring the role of

factors such as smoking and obesity and underestimating the risks of

aspirin itself.

Of particular concern is aspirin's long-known tendency to cause

bleeding, which apparently led to a small but significant rise in the

rate of serious strokes in the new study's aspirin takers.

While calling the new findings on heart attack "striking" and "very,

very significant," Dr. Claude Lenfant, director of the National Heart,

Lung and Blood Institute, also urged caution.

"I don't want everybody to go out to the drugstore and buy five

pounds of aspirin and start taking it every day," Lenfant said.

His caution is echoed by the researchers involved with the

aspirin-heart disease study.

"No one should go out and just start taking aspirin," said Dr.

Charles H. Hennekens, the principal investigator of the study and

associate professor of medicine at Harvard Medical School and the

Brigham and Women's Hospital in Boston.

Hennekens himself was one of the 22,071 doctors who volunteered to

participate in the aspirin study by taking a little white pill every

other day -- either a Bufferin tablet of buffered aspirin or an

identical-looking but ineffective substitute called a placebo.

Participants were not told which tablet they were receiving, and

Hennekens learned only last week that he was in the placebo group.

To underscore the importance of consulting with a physician,

Hennekens said he would talk to his own doctor before deciding whether

to begin taking an aspirin every other day as a preventive measure

against heart attack.

"Any doctor who treats himself has a fool for a patient," Hennekens

said. The decision to take or not to take aspirin, he emphasized, should

take into account a patient's "complete risk profile."

For example, as a slightly overweight 45-year-old male, Hennekens has

a one in five statistical chance of suffering a heart attack by age 60.

It's not that simple, however. His family history includes diabetes on

his mother's side, and his father died of a heart attack at age 56 --

factors that could increase his risk.

But Hennekens has also normal blood pressure, a very low blood

cholesterol level of 153 and, unlike his father, he does not smoke. He's

also a nationally ranked squash player in the over-40 age group.

So, given his own study's recent findings, should he start taking

aspirin to lower his risk of heart attack? "I'm going to see my doctor,"

he said.

The massive, five-year Physicians' Health Study was scheduled to end

in 1990, but the aspirin trial was halted early because preliminary

results showed a "statistically extreme beneficial effect" on heart

attack. The findings were reported in last week's New England Journal of

Medicine. A second part of the study, measuring the possible effect of a

form of vitamin A called beta-carotene on cancer risk, continues.

Heart attack is the leading cause of death in the United States,

claiming more than half a million lives a year.

Among the physicians in the study, there were 171 nonfatal heart

attacks in the placebo group, compared with only 99 in the aspirin

group. There were 18 fatal heart attacks in the placebo group, but only

five in the group taking aspirin.

Experts cautioned that this does not mean aspirin has any effect on

the underlying process of heart disease, the narrowing of the coronary

arteries that supply the heart. What the results do suggest is that

aspirin helps prevent heart attacks by inhibiting the formation of blood

clots that can block the blood flow in a narrowed blood vessel. It does

so apparently by keeping blood particles called platelets, which are

crucial in the clotting process, from clumping together.

The group studied, though large, was not a typical cross-section of

the nation's population. It comprised healthy male physicians ranging in

age from 40 to 84. Only 11 percent were smokers, and none was being

treated for heart disease, cancer, liver disease, kidney disease or

ulcers.

"What scares me," said Lenfant of the National Heart, Lung and Blood

Institute "is that people may not appreciate that this was a very

particular population we studied. These were physicians. They were a

very healthy, health-conscious group."

The entire group, during the nearly five years of the study, had only

88 deaths from all forms of cardiovascular disease. In a cross-section

of American males, the same-sized group would be expected to include 733

such deaths.

Despite the dramatic difference in the rate of heart attack between

the study's two groups, the death rate remained the same. Researchers

said it is logical to assume that a drop in the mortality rate would

eventually result from the decline in heart attacks in the aspirin group

-- but perhaps not for another decade or more.

"We couldn't get any assurance on that probably until the year 2000,"

he said. Given the dramatic early results on heart attack prevention, he

said, it would have been unethical to prolong the study indefinitely in

pursuit of mortality data.

"If these were 22,000 rats in a maze {instead of physicians}, we'd

keep the study going on for 10 more years," Hennekens said.

A second study, of regular aspirin use in 5,000 British physicians,

was also reported last week and suggested a contrary finding: no effect

on the heart attack rate. But the study's own authors discounted the

significance of their finding because of the relatively small size of

the study and said the American study "carries more weight."

Unfortunately, the same anti-clotting effect, which seems to offer

some protection against heart attacks, poses a hazard by preventing

clotting when it is needed -- for example to stop bleeding in an ulcer

or during surgery or when a blood vessel in the brain begins to leak.

"Anything that decreases the tendency to clot is going to increase the

tendency to bleed," Hennekens said.

Normally, a tiny leak, or hemorrhage, in a blood vessel in the brain

would be closed off by the normal clotting factor in the blood. But

aspirin could cause such a leak to keep bleeding enough to cause a

hemorrhagic stroke.

Hemorrhagic strokes are much more likely to be

fatal than other kinds of strokes, known as ischemic strokes. Like heart

attacks, ischemic strokes are caused by a clot or blockage in the blood

vessels. That can prevent oxygen-rich blood from reaching the brain.

Though the total number of strokes in the study's two groups was

similar, the number of serious or fatal hemorrhagic strokes was higher

in the aspirin group than in the placebo group, by 10 to two.

"Aspirin is not the benign drug many people think it is," Lenfant

said. "You and I take a tablet when we get a headache or a hangover." As

effective as it can be for pain relief, he added, aspirin can cause or

aggravate conditions such as stomach bleeding and ulcers. In children

with fevers, it has been linked to a rare illness called Reye syndrome.

"It's not like taking a cup of tea," Lenfant said.

Lenfant said he would consider prescribing aspirin as a preventive

measure only in patients who were at above-normal risk because of other

factors.

"But first I would work on lowering your blood pressure and your

cholesterol," he said. "I might then also prescribe aspirin, but only as

part of a comprehensive regimen."

Harvard's Hennekens noted that a smoker could reduce his risk of

heart attack by 80 percent by stopping smoking -- a much bigger risk

reduction even than the 47 percent decrease from aspirin use in healthy

males in the study.

"Aspirin should never be perceived as a substitute for reducing other

risk factors," said Dr. Thomas Bryant, president of the Aspirin

Foundation, an association of companies that make and sell aspirin and

aspirin products.

The dose of aspirin in the Physicians Health Study is quite small:

one tablet every other day. But some doctors worry that consumers will

jump to the conclusion that a higher dose would be even more effective

in reducing the chance of heart attack.

"The natural inclination in this world is to believe that if a little

bit is good, a whole lot must be better," said Dr. Howard E. Morgan,

senior vice president for research at the Geisinger Clinic in Danville,

Pa., and president of the American Heart Association. "That could cause

problems."

Americans take an estimated 80 million aspirin tablets a day, and

aspirin is also an ingredient in many other nonprescription pain

relievers. Drug companies that make and sell aspirin have already

produced advertisem*nts touting the new findings as yet another reason

to consider buying their product.

Aspirin is nothing new. The pain-relieving properties of a naturally

occurring form of aspirin in willow bark were noted by the physician

Hippocrates in ancient Greece. The drug has been sold in tablet form

since 1899.

Previous studies have shown that aspirin can help protect heart

attack survivors against a second heart attack, but the Physicians'

Health Study is by far the largest ever of aspirin and heart attack and

the first in healthy people.

"It fits in quite well with our thinking about how people get heart

attacks," said Dr. Lawrence S. Cohen, professor of medicine at Yale

University School of Medicine. "It's another piece in the puzzle."

Cohen is a member of the data monitoring board that met twice a year

to review the Physicians' Health Study's ongoing results and decided

unanimously last Dec. 18 that the aspirin findings were so striking that

the study should be halted and its findings reported early.

For his own patients, Cohen said he will recommend an every-other-day

aspirin dose for healthy middle-aged or elderly men, as well as for

women and younger men who are at high risk of heart attack because of

any combination of smoking, high cholesterol, diabetes or family history

of heart disease.

Cohen said the stroke results were "a cause for concern," but he

emphasized that the numbers of strokes were "very small in comparison to

the numbers of heart attacks prevented in the study."

There were six deaths from stroke in the aspirin group, compared with

two in the placebo group.

The apparent elevated risk of stroke in the aspirin group is of

particular concern to patients with high blood pressure that is not

controlled by drugs, Cohen said.

Do the findings in the all-male study apply to women as well? It's a

pretty good hunch," Cohen said. But he pointed out that the likelihood

of benefit is less in women because the odds of suffering a heart attack

are much lower for middle-aged women.