title=avandia alt="" align=left
blockbuster type 2 diabetes drug Avandia raises users odds for heart attack and
heart failure and should be removed from the market, according to confidential
The New York Times on Saturday reported on documents from the U.S. Food and
Drug Administration that find that if people now taking Avandia (rosiglitazone)
switched to a similar medication, Actos, about 500 heart attacks and 300 cases
of heart failure would be eliminated each month. And in a report from the
Institute for Safe Medication Practice, Avandia was linked to 304 deaths in the
third quarter of 2009 alone, the highest for any prescribed drug in that time
period, the Times reported.
In one of the FDA documents, dated October 2008, Drs. David Graham and Kate
Gelperin drug safety officials at the agency agreed that rosiglitazone
should be removed from the market.
The reports, obtained early by the Times, are yet another chapter in
Avandias checkered history. The drug was once taken by millions worldwide, but
that changed after a study released in early May of 2007 by the Cleveland Clinic
suggested that Avandia carried cardiovascular risks. That study, which included
more than 28,000 people, found that Avandia increased a users odds of heart
attack by 43 percent compared to those not taking the medicine.
At the time, Dr. Bruce M. Psaty of the University of Washington who also
co-wrote an accompanying editorial in the New England Journal of Medicine
urged the FDA to restrict access to Avandia and cited both the agency and the
drugs maker, GlaxoSmithKline, for poor oversight.
The primary problem here is that studies that were needed early on about the
health benefits of this drug were never done, Psaty told HealthDay. As a
result of the failure of the sponsor to do long-term clinical trials to show
health benefits, as a result of the failure of the FDA to insist on it, we have
data that are weak.
Following on the Cleveland Clinic study, the FDA demanded black box
warnings on labeling for both Avandia and Actos, warning of a potentially
heightened risk for heart failure. However, other studies found no raised level
of heart risk, and at the time the agency said it had not reached a definitive
conclusion on the data.
In November of the same year, the FDA updated Avandias labeling to include a
caution regarding heart attack risk. At the time, Dr. Janet Woodcock, acting
director of the FDAs Center for Drug Evaluation and Research, said that, we
are keeping Avandia on the market because we have concluded there isnt enough
evidence to indicate that the risk of heart attack is higher for Avandia than
other type 2 diabetes treatments.
The story got more complicated in 2008, as a number of studies emerged tying
the use of Avandia to increased bone fracture risk.
Throughout 2009, more studies reiterating the drugs heart risks also came to
light, including one published in the BMJ suggesting that Avandias risk for
heart failure seemed to outstrip those of its related rival, Actos.
By that point, most clinicians [had] stopped using Avandia some will use
Actos instead or go to another class completely, Dr. Carl J. Lavie, medical
director of cardiac rehabilitation at the Ochsner Heart and Vascular Institute
in New Orleans, told HealthDay at the time.
The emergence of the leaked documents on Saturday comes at a time when
officials within the FDA seem to be at loggerheads over whether to ban Avandia
or not, the Times reported. The newspaper said that some officials believe that
safer alternatives exist, while others say the evidence on Avandias safety is
conflicted and the drug should remain available as a treatment option.
Trying to sort things out, in December of 2009 Woodcock asked officials at
the FDA to convene another advisory committee to determine whether Avandia
should remain on the market, with a decision expected this summer.
In the meantime, a bipartisan Senate investigation overseen by Sen. Max
Baucus (D-Mont.) and Sen. Charles E. Grassley(R-Iowa) has pored over 250,00
internal documents from GlaxoSmithKline. The investigation has placed much of
the blame for the Avandia debacle on the company, contending that it neglected
to warn patients for years of the drugs dangers.
G.S.K. executives attempted to intimidate independent physicians, focused on
strategies to minimize or misrepresent findings that Avandia may increase
cardiovascular risk, and sought ways to downplay findings that a competing drug
might reduce cardiovascular risk, according to the Senate investigation report,
which is slated for release Monday but was obtained early by the Times.
Speaking to the newspaper Friday night, agency commissioner Dr. Margaret
Hamburg said that, I await the recommendations of the advisory committee.
Meanwhile, I am reviewing the inquiry made by Senators Baucus and Grassley and I
am reaching out to ensure that I have a complete understanding and awareness of
all of the data and issues involved.
In a statement released Saturday, GlaxoSmithKline said it rejects the
conclusions about the safety of Avandia (rosiglitazone) as reported in that
days Times story.
Contrary to the assertions in the story, and consistent with the
FDA-approved labeling, the scientific evidence simply does not establish that
Avandia increases ischemic cardiovascular risk or causes myocardial ischemic
events, the company said. In 2007, the FDA considered all the available
scientific evidence on Avandia, including Dr. Grahams assertions of elevated
heart attack risk and demands that the product be withdrawn. Based on the
scientific evidence and a recommendation by an independent advisory committee of
experts convened by the FDA, the agency has ruled that Avandia remain available
to patients for the treatment of Type 2 diabetes.
In the wake of the controversy, GlaxoSmithKline had been directed by the FDA
to conduct a trial comparing rates of heart attacks, strokes and heart-linked
deaths among users of Avandia, Actos or a placebo. But according to internal
documents accessed by the Times, Graham and Gelperin characterized the study,
called TIDE, as unethical and exploitive, with patients being given Avandia
despite the fact that it appears to come with greater risks and no added benefit
One of the Graham/Gelperin reports dated October 2008 concludes that,
Although the proposed TIDE trial is motivated by a desire for definitive
answers regarding the cardiovascular safety of the drug rosiglitazone, the
safety of the study itself cannot be assured and is not acceptable.
However, other FDA officials overruled those concerns and TIDE is still
enrolling patients, with preliminary results expected by 2014. Responding to the
criticism, GlaxoSmithKline noted Saturday that, TIDE has been approved by an
independent review board and appropriate safety boards that are responsible for
assessing the safety of conducting the trial.
The ongoing controversy has dampened patients and physicians enthusiasm for
Avandia. According to the Times, while sales of the drug topped $3.2 billion in
2006, those numbers plummeted soon after the first studies suggesting risk
emerged a year later.
Still, hundreds of thousands of people still take Avandia, the Times noted.
GlaxoSmithKlines patent on the drug expires in 2012.