Calm Urged for Avandia Patients

even if the drug really does increase the risk of heart
attack, some medical experts caution.

Experts -- including the doctor who sounded the Avandia alarm -- tell WebMD
there's no need for patients to panic.

The concern comes from the early release of a report in The New England
Journal of Medicine
(NEJM) suggesting that Avandia increases a
diabetes patient's already high risk of heart attack by 43%.

Researcher Steven Nissen, MD, is chairman of Cleveland Clinic's
cardiovascular medicine department. Nissen, past president of the American
College of Cardiology, was one of the first doctors to raise the alarm about
the heart risks posed by Vioxx.

Nissen says his findings are valid, but he warns that the data are not
definitive and must be confirmed by further studies.

"What patients need to know is there is some evidence of cardiovascular
harm from Avandia -- but there is not any reason to panic," Nissen tells
WebMD.

Since news of the Nissen study broke on Monday, frightened diabetes patients
have flooded their doctors' phone lines, says Luigi F. Meneghini, MD, MBA,
director of the diabetes treatment center at the University of Miami.

"The way this has been presented has been completely out of proportion.
It has created a lot of hysteria," Meneghini tells WebMD. "Patients
have stopped taking their medications. They don't want to be on this medication
any more."

Andrew Drexler, MD, director of UCLA's Gonda Diabetes Center, is seeing the
same reaction.

"We're definitely getting flooded with calls. Everybody wants to know
what to do," Drexler tells WebMD.

So here's what these experts say you should do:


  • If you are currently taking Avandia, do not stop taking the drug.

  • If you are taking Avandia and have already had a heart attack or heart
    trouble, call your doctor to schedule an appointment as soon as possible.


If you don't already have a heart problem, the risk from Avandia -- if there
truly turns out to be one -- is not so great that you have to see a doctor
right away. But do make an appointment to discuss the issue.




Calls for Calm in Wake of Avandia Alarm



At least since 2005, the FDA has been aware of the possible heart attack
risk of Avandia. But there's conflicting evidence, including a study of more
than 30,000 diabetes patients in a large health maintenance organization (HMO)
that found no extra heart attacks among Avandia patients.

For this reason, the FDA has decided not to pull Avandia from the market.
Instead, the FDA is working as fast as it can to pull together an expert
advisory panel to weigh all the available data.

The FDA warns patients not to stop taking Avandia on their own. Drexler
agrees.

"When people read these stories about heart attack risk, they often stop
taking their diabetes drugs," he says. "The resulting deterioration of
their care can be very detrimental. Everyone says, 'Consult your doctor before
stopping any prescribed medication,' but we really must stress this point more
strongly."

An editorial released on Wednesday by the editors of the British medical
journal The Lancet takes the unusual step of criticizing the NEJM
for the "urgency" in the tone of the Nissen paper and an accompanying
editorial.

"To avoid unnecessary panic among patients, a calmer and more considered
approach to the safety of [Avandia] is needed," the Lancet editors
write. "Alarmist headlines and confident declarations help nobody."

Drexler notes that an ongoing study, the RECORD clinical trial, is studying
whether Avandia truly causes heart problems. But the study will not be finished
until the end of 2008 or 2009, depending on how many patients develop heart
disease.

Another study, the ACCORD trial, which is studying outcomes in 10,000
patients with type 2 diabetes, should also reveal the true risks and benefit
of Avandia. That trial, too, is years from completion.

GlaxoSmithKline, the company that makes Avandia, says these trials are being
monitored by independent safety boards. Patients should be reassured by the
fact that these safety boards have seen no reason to stop the studies, says GSK
Chief Medical Officer Ronald Krall, MD.

"The data safety monitoring boards have done an interim analysis very
recently and have reassured us there is nothing in that analysis that should
affect the conduct of the study or be of concern," Krall tells WebMD.
"They have looked at the specific issues raised by Dr. Nissen. Because
cardiovascular events are the RECORD study endpoints, they have looked at them
in great detail."




Calls for Independent Look at Avandia Risk



Drexler says these safety boards should go one step farther and do a
separate and specific analysis to ensure that no signal of heart risk has been
missed for any group of patients.

"We are interested not just in whether the drug helps some patients, but
in whether the drug is riskier for some patients," he says. "If the
Nissen paper is valid, you should be able to see these differences by
now."

Drexler believes that patient faith in Avandia can only be restored if GSK
hands over all the data it has to an outside panel of experts for independent
review.

"GSK should ask some organization, preferably the Endocrine Society, to
put together a group of scientists chosen by the organization, and open up
their files without restriction and let that group study it," he says.
"Unless they do that, I think they are going to have a very hard time
selling this drug."

GSK's Krall says this is unnecessary as the FDA is already assembling an
expert panel. He promises that GSK will make all of its data available to the
FDA panel.

"We will try to share everything we have with the community of
physicians," he says.

Nissen is skeptical.

"I have been discussing this with GSK, and they do not want to have a
complete analysis done of all their data," he says. "If they are going
to clear the air, now is the time. The reason they don't want to do it, I
think, is they have already done it themselves and don't like the
results."

Drexler says GSK's reassurances have so far been more of a public relations
effort than a scientific effort. Krall bristles at that suggestion.

"There are a number of scientific manuscripts in preparation, that have
been in preparation, that will help communicate to the scientific community the
data that the FDA and European regulatory authorities already have seen,"
Krall says. "All of this is not under GSK control. Some of these studies
have been done by external academic experts. It is they who are writing the
actual manuscripts. There is an interest in this scientific data, and we are
trying to respond as quickly as we can with scientific communications."

Avandia gained FDA approval in 1999. That approval was based on the drug's
ability to lower diabetes patients' blood-sugar levels.

"Why do we control blood sugar in diabetes? The reason is to control
complications of diabetes," Nissen says. "Avandia has never been shown
to control any diabetes complication. They have had eight years to show a
health-outcome benefit. Yet they've shown no reduction in microvascular [eye,
kidney, and extremity] complications and no reduction in cardiovascular [heart]
outcomes."

Krall says such studies began very soon after Avandia approval.

"It takes studies of 10 years' duration or more to show clinical
endpoints," he says. "It took 10 years to see clinical results in
studies of [the older diabetes drugs] metformin and sulfonylura. It is not fair
to expect those results yet for Avandia. What is clear is that if you do manage
[blood sugar levels], you do see those endpoints in 10-plus years'
time."




Alternatives to Avandia



Another drug in he same class as Avandia, Actos, has already been shown to
lower -- not raise -- the risk of heart disease in diabetes patients.

"It may be hard to justify continuing to prescribe Avandia if there is
an alternative, Actos, that does not have same risk profile," Meneghini
says. "So in terms of new Avandia prescriptions, I don't think so. It is
not so much a clinical decision as a liability decision. Because if a patient
says, 'I want to come off the drug,' and his doctors says, 'No, continue taking
it,' and the patient has a heart attack -- for whatever reason -- well, you can
imagine what comes after that."

But Meneghini still says Avandia is helping some patients.

"In terms of patients currently on the drug, if they have had a good
response in terms of blood sugar control, and no prior cardiovascular event, I
don't see why they should not continue," he says. "In those with a
history of heart trouble, maybe they should consider a change. Insulin therapy
is one of the cleanest options we have at this point in time."

And, of course, there are nondrug treatments, too.

"Avandia and Actos reduce insulin resistance. You can achieve that with
physical activity and losing weight, especially around the waist,"
Meneghini says. "These are healthy ways to achieve better blood sugar
control without side effects. This should be adopted by anybody. After all, the
mainstay of diabetes treatment is healthy weight, healthy diet, and lose some
weight if you are overweight."



By Daniel DeNoon
Reviewed by Louise Chang
B)2005-2006 WebMD, Inc. All rights reserved

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