took deadly toll: study
By CAROLYN ABRAHAM
Jan 25, 2005
, the blockbuster arthritis and pain medication
pulled off the market last September, could have killed more than 40,000
people in the United States, according to an FDA scientist who has said his
employer silenced his earlier warnings about the drug's safety.
David Graham, associate director of
science for the U.S. Food and Drug Administration's Office of Drug Safety and
lead author of a study published on-line by The Lancet yesterday, found that
raised a person's risk of coronary heart disease by
34 per cent, compared with other anti-inflammatory drugs, including
, its onetime rival in the class of drugs known
as cox-2 inhibitors.
also been linked to heart attacks at high doses).
Dr. Graham and colleagues estimate that
during the five years
was sold in the
"It's a huge number," said Dr.
Graham, now widely known as a whistle-blower scientist.
"In the future, when trials show that
a new treatment confers a greater risk of a serious adverse effect than a
standard treatment, we must be much more careful about allowing its
Dr. Graham said in an interview yesterday
that it was fair to extrapolate the
"The population of
Such an extrapolation would suggest
could be associated with as many as 4,000 to 7,000
a senior scientist with the Institute for Clinical Evaluative Sciences in
"Do I believe those numbers? Not
really," he said. "They could be higher or they could be lower.
It's dangerous to extrapolate a number from the data."
Certain factors might skew the
said. For example, he
noted most of the heart problems uncovered were linked to patients taking
at doses higher than 25 milligrams a day.
As well, he said, people taking
in the study may have been at higher risk of
coronary disease: "People who use traditional NSAIDS [non-steroidal
anti-inflammatory drugs such as ibuprofen] are typically healthier."
He said if
had such a dramatic effect on heart attack rates, researchers here would have
detected a spike. Instead, he said, none was apparent.
added: "I think David Graham's work should be commended. It shows in a
reasonably convincing manner that there's a problem there."
No one from Health
That move followed evidence that
doubled the risk of heart attacks and strokes in a
clinical trial studying whether the drug could prevent colon cancer. Other
studies have suggested that the drug, which blocks an enzyme linked to pain
and swelling, contributes to blood clotting and hypertension. But the cancer
study was not the first to point to the heart risks of taking
Dr. Graham decided to lead a
study after a large trial intended to highlight the
gastrointestinal safety of the drug instead suggested it carried five times
the risk of heart problems compared with naproxen, an older anti-inflammatory
and pain-killing medication.
At the time, Merck officials suggested
naproxen actually protected the heart, which made it appear as though
was having a damaging effect. Dr. Graham decided to
He and colleagues analyzed data from 1.4
million people between the ages of 18 and 84 in
Not only did they find that naproxen did
not protect against serious heart disease, they uncovered the risk that
But Dr. Graham said that his supervisors
at the FDA discouraged him from presenting his findings to a drug-safety
meeting last summer. As well, he said, "They tried to block it from
"I was threatened with severe
consequences if I went forward. I took that to mean I would be fired,"
said Dr. Graham, who testified at a U.S. Senate committee hearing last fall
that he felt the FDA fumbled its duties on the
FDA officials deny Dr. Graham's
allegations and say they feel Dr. Graham's study required further review
before it could be submitted.