Avandia, the popular anti-Type II diabetes drug, increases heart attack risk by 43% -- and increases risk of death from heart disease by 64%, says a new study.
However, the overall risk was small. Among the 15,560 Avandia patients there were 86 heart attacks and 39 deaths, compared with 72 heart attacks and 22 deaths among the 12,283 patients not taking Avandia.
The new warning comes from an analysis of publicly available, short-term clinical studies comparing Avandia to other diabetes treatments. It shows that.
"In susceptible patients, [Avandia] therapy may be capable of provoking myocardial infarction [heart attack] or death from cardiovascular causes after relatively short-term exposure," suggest study investigators Steven Nissen and Kathy Wolski. Nissen chairs the Cleveland Clinic's department of cardiovascular medicine; he is past president of the American College of Cardiology.
Avandia is sold by itself and, as Avandamet and Avandaryl, in pills that combine Avandia with other diabetes medications. The findings do not appear to immediately affect Actos (made by Takeda Pharmaceuticals), a diabetes drug in the same class as Avandia.
The Food and Drug Administration (FDA) in 1999 approved Avandia on the basis of clinical trials showing that the drug could reduce blood-sugar levels in people with type 2 diabetes. Diabetes has been linked to both microvascular problems (problems of tiny blood vessels) such as blindness, kidney failure, and loss of circulation in the extremities. It has also been linked to heart disease.
But none of the trials on which Avandia was approved showed that the drug actually prevented the greatest threats to people with diabetes: microvascular problems, heart disease, or heart death.
In a strongly worded editorial accompanying the study, University of Washington researcher Bruce M. Psaty says the Nissen study means there's no good reason for most patients to take Avandia.
"There is little evidence for using this drug," Psaty said in an interview. "The purpose of reducing blood sugar is to prevent cardiovascular events. Now the possibility of cardiovascular benefit associated with Avandia appears remote -- indeed, it appears linked to harm. So the rationale for prescribing it at this time is just not clear."
Still Psaty warned patients taking Avandia not to just stop using it. They should continue taking the drug until they can discuss the matter with their doctor.
"This is not an immediate risk. It is the absence of an expected benefit and the possibility of harm over the years...Patients should talk with their doctors and see if they are getting the benefit they expected. Doctors can look at the data and say whether there is a compelling reason for them to prescribe this drug. I don't think there is," he said.
The drug giant, had posted a fall in sales and profits for the first quarter of the year due to a strong pound and tough generic competition in the US.
But the company said its two best-selling drugs - Advair for asthma and Avandia for type 2 diabetes - performed well. Total sales of Advair, or Seretide as it is known in Europe, were up 11% to £835m, and sales of Avandia grew 19% to £414m.
It strongly repudiates the study, but a previous study by the GSK itself had showed about a 30% increase in heart risk to patients taking Avandia.
The company points out though that a study of 33,000 patients in a managed-care database showed no increased heart risk in patients taking Avandia. Both this study and the GSK analysis were given to the FDA in August 2006.
Ongoing, long-term studies also support Avandia safety, says GSK chief medical officer Ronald Krall.
"I want to be very clear that we are confident in the benefit/risk profile for Avandia. We believe that if it is used according to the directions incorporated into U.S. and European labels, it is an important treatment for patients with type 2 diabetes," Krall says in a news release. "We believe that important evidence coming from long-term studies supports the safety of Avandia."
Meanwhile on Monday, Henry Waxman, a Democratic senator from California and chairman of the House Oversight and Government Reform Committee, invited Glaxo CEO Jean-Pierre Garnier, FDA Commissioner Eschenbach and Dr. Steven Nissen, the author of the NEJM article, to testify before the committee on June 6.
"This is the latest reminder that FDA isn't effectively monitoring the safety of drugs used by millions of Americans once they are on the market," says Waxman. "As early as March, the FDA knew Avendia's risks but it inexplicably failed to act. The American people deserve to know why the FDA failed to take action to warn doctors and patients."
According to Representative John Dingell, the chairman of the House Energy and Commerce Committee, which oversees consumer protection, the controversy surrounding Avandia is likely to have an impact on the House's look at FDA reform.
"It is incredible that the agency charged with protecting the public health has such a poor record when it comes to post market drug safety," he says. "Regrettably it is incidents like this that demand legislative changes in the way FDA deals with drug safety. The Committee will address these dangerous shortcomings while writing legislation to reauthorize [prescription drug legislation]."
Dingell and Waxman had already been alerted to the potential health risks posed by Avandia. Earlier this month, they and several other House members asked the FDA to inform them of the agency's plan to protect the public from the drug's potential harm.
The FDA has issued a safety alert for Avandia, but for the moment it is not asking Glaxo to take any specific action. FDA officials were not immediately available for comment.