May 21, 2007 -- Millions of Americans taking the highly promoted diabetes drug Avandia could be putting themselves at risk for deadly heart problems, according to new research.
The findings are the latest volley in a spate of criticism over the U.S. Food and Drug Administration's drug approval and regulation procedures.
The new concerns surfaced Monday in a review of previous research published in the New England Journal of Medicine.
The analysis revealed that those taking the widely used drug experienced a 43 percent higher risk of heart attacks and a 64 percent increased risk of dying from heart disease
Lead author of the analysis and president of the American College of Cardiology, Dr. Steven Nissen, told ABC News medical correspondent John McKenzie, in an interview for "World News" that the findings are "alarming."
"It needs to be confirmed with other analyses, but if the data hold up — and I believe that they will hold up — it does represent a huge public health concern," he said.
The review of data encompassed 42 clinical trials, involving a total of 27,000 diabetic patients.
Some doctors worry that this further demonstrates how risks associated with many drugs may slip through the cracks when it comes to approvals.
"Both the FDA and the drug company presumably had this data in hand," Dr. David Nathan, director of the diabetes center at Massachusetts General Hospital told McKenzie. "So why didn't they ever look at it the same way Dr. Nissen and his colleagues did?"
Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston, agrees. "As [Nissen] notes in his paper, they have access to all these data, so why did they not find this?"
In a conference call Monday afternoon, Dr. Robert Meyer of the FDA's Office of Drug Evaluation II, Center for Drug Evaluation and Research, said that it has had the heart attack data since August of last year.
"We decided that we needed to reanalyze the complex data set ourselves to make a better informed decision about what the meaning of those data might be," he said.
In an accompanying commentary, Dr. Bruce Psaty of the University of Washington and Dr. Curt Furberg of Wake Forest University said regulators must take action.
"The rationale for prescribing [Avandia] at this time is unclear," the editorial reads. "Unless new data provide a different picture of the risk-benefit profile, regulatory action by the Food and Drug Administration is now warranted."
Avandia Widely Used
The drug, manufactured by GlaxoSmithKline is intended to help patients with diabetes control their blood sugar levels.
Since its approval by the FDA in 1999, more than 6 million people worldwide have taken Avandia.
In total, 60 million prescriptions have been written for the drug, and it generates annual sales worth $3 billion annually.
Despite the review, the FDA is not asking GlaxoSmithKline to take any specific action at this time. And there are no plans yet to strengthen warnings on the product's labeling, which already include risks to the heart.
In fact, the most recent labeling change for Avandia in 2006 included a new warning about a potential increase in heart attacks and heart-related chest pain in some individuals using the drug.
Meyer defended the regulatory body's actions on Avandia. "We don't have clear regulatory or clinical advice message as of today," he said, adding that the FDA is "also in possession of unpublished and published data that could lead to quite a different conclusion."
Meyer added that the FDA is very close to completing its own meta-analysis on the drug.
GlaxoSmithKline stood behind the safety of its drug in its own statement issued Monday, maintaining that its benefits outweigh any possible risks.
"GSK strongly disagrees with the conclusions reached in the NEJM article, which are based on incomplete evidence and a methodology that the author admits has significant limitations," the statement reads.
Still, physicians say the article and its accompanying editorial provide compelling evidence that more review is needed for the drug.
"In over 40 years of reading NEJM editorials, this is as strong — in criticism of the FDA and using lab measurements instead of clinical outcomes for approval — as I have ever read," says ABC News medical editor Dr. Timothy Johnson. "The writers clearly believe that the current approval process and post approval surveillance are not adequate."
Dr. Sidney Wolfe, director of the health research group for the consumer organization Public Citizen, said in a statement issued Monday that the drug should be considered too dangerous for use.
"[W]ithin the first six years of approval, there have been 689 cases of heart failure reported to the FDA in patients using the drug," Wolfe said.
"Despite prior knowledge of serious cardiac problems, the FDA has failed to require Glaxo to adequately warn about the dangers of this drug that should be, at best, a last-choice treatment for Type II diabetes. … We strongly urge patients — as we have for almost two and a half years — not to use this drug."
Others says the new evidence signals the need for more stringent approval guidelines in general.
Dr. Susan Louisa Montauk, professor of clinical family medicine at the University of Cincinnati College of Medicine, says that if the FDA is not more vigilant in its approval process, "[W]e will have dozens of Avandias every year very soon ... drugs we are confused about that may save some lives and shorten others."
A Broader Call for Action
The analysis has already prompted Rep. Henry Waxman, chairman of the House Committee on Oversight and Government Reform, to announce a hearing for June 6, 2007, on the FDA's role in evaluating Avandia's safety.
As for now, FDA's Meyer says the strongest action that patients on the drug should take is to talk to their doctors about potential risks, especially if they have a history of heart problems.
ABC News medical correspondents John McKenzie and Brian Hartman contributed to this report.