FDA's Weak Response To May 2007 News That Avandia Increases The Risk Of Heart Attacks And Cardiovascular Deaths

No Avandia Recall or Suspension of Sales While FDA Assesses Situation

Avandia and Heart Attack Risk

On May 21, 2007 we learned that the diabetes drug Avandia (rosiglitazone), from GlaxoSmithKline, may increase the risk of heart attacks and cardiovascular deaths when the New England Journal of Medicine (NEJM) first published on its web site an article about a new meta-analysis of Avandia data by Dr. Steven Nissen and his co-author Kathy Wolski.

Nissen and Wolski conducted their new analysis of pre-existing Avandia data in order to assess the effect of Avandia on "cardiovascular outcomes" for diabetics who used this GlaxoSmithKline drug for long-term therapy. Knowing the effect of any diabetes therapy, such as Avandia, on cardiovascular outcomes is particularly important given that 65% of deaths in diabetic patients are from cardiovascular causes.

The findings from this new analysis by Nissen and Wolski are disturbing insofar that they show patients taking Avandia had a 43% higher risk of heart attacks and a 64% elevated rate of cardiovascular death. The reason that these findings are disturbing is because of the previously known fact that patients with diabetes already experience a high incidence of cardiovascular events due to their disease.

In the NEJM article about their new analysis of Avandia data, Nissen and Wolski state that while the exact biological mechanisms causing increased heart attack and cardiovascular death risks in diabetic patients using Avandia are unknown at present, they speculate that it could be due an adverse effect on lipid levels, precipitation of heart failure, and a reduction in hemoglobin levels.

FDA Response

In a statement issued that same day that the NEJM Avandia article was first published online, May 21, 2007, the agency noted these several points:

• Since Avandia was approved in 1999, the FDA has been monitoring several heart-related adverse events -- such as fluid retention, edema, and congestive heart failure -- based on "signals" seen in previous controlled clinical trials and from postmarketing reports;
• The Avandia package insert, or label, when it was last changed in 2006, added a new warning about a potential increase in heart attacks and heart-related chest pain in some individuals using Avandia;
• The agency is aware of this new meta-analysis of Avandia data by Nissen and Wolski, but there is other published data and unpublished data from long-term clinical trials that provide contradictory evidence about the risks in patients treated with Avandia; and,
• The FDA's analysis of all available Avandia data is ongoing, and the agency has not confirmed the clinical significance of the increased risk reported by Nissen and Wolski in the context of these other studies; accordingly, at this time the agency is not asking GlaxoSmithKline to recall Avandia, suspend sales, nor take any other particular action.

If all of this sounds more like a non-response by the FDA, add to the several points above this rather vague statement which was included in the agency's May 21, 2007 press release, entitled "FDA Issues Safety Alert on Avandia":

“FDA is carefully weighing several complex sources of data, some of which show conflicting results, related to the risk of heart attack and heart-related deaths in patients treated with Avandia," said Steven Galson, director of the FDA's Center for Drug Evaluation and Research. "We will complete our analyses and make the results available as soon as possible. FDA will take the issue of cardiovascular risk associated with Avandia and other drugs in this class to an advisory committee as soon as one can be convened," he added.

Guidance for Avandia Patients

This FDA press release did, however, provide some good medical guidance to diabetics in this time of uncertainty:

Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes.

Let's hope for the sake of these patients that the FDA is able to determine, soon, the issue of whether or not Avandia is an unsafe drug.