A recent poll by MedPage Today found that only 9% of the doctors who responded said they would continue to prescribe the diabetes drug rosiglitazone, sold as Avandia and Avandamet by GlaxoSmithKline, without reservation since an FDA advisory panel acknowledged that the drug increases heart risks for patients with Type II diabetes.
The results published on August 6, 2007, reported that 36% of the responding doctors said they would continue to prescribe the drug for select patients, but 55% said they will no longer prescribe it and 23% said the drug should be taken off the market.
On July 30, 2007, the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the FDA met to discuss the risks associated with Avandia and concluded that the use of the drug was associated with a greater risk of myocardial infarction, angina, or sudden death than placebo, or other diabetes drugs such as metformin or sulfonylureas.
In the end, the panel recommended that Avandia should remain on the market but said stronger warnings should be added to the label and that extensive educational efforts should begin immediately.
However a new study in the September 11, 2007 Journal of American Medicine that found Avandia increased the risk of heart attack by 42% and doubled the risk of heart failure has researchers at Wake Forest University in North Carolina, led by Dr Sonal Singh, an assistant professor of internal medicine, once again calling for the removal of the drug from the market.
"These data suggest a reversal of the benefit-to-harm balance for Avandia present at the time of approval," the study authors wrote. "Regulatory agencies ought to reevaluate whether Avandia should be allowed to remain on the market," they state.
They researchers also warn that health plans and doctors should not wait for regulatory action. "They should avoid using Avandia in patients with diabetes who are at risk of cardiovascular events, especially since safer treatment alternatives are available," the authors conclude.
A second study published in the same issue of JAMA, conducted at the Cleveland Clinic, analyzed data from clinical trials on patients taking Actos (pioglitazone), a drug in the same class as Avandia, and found it to be more beneficial to diabetics.
To reach their conclusion, the lead author, Dr A Michael Lincoff, vice chairman for research in the department of cardiovascular medicine at Cleveland Clinic, and co-author, Dr Steven Nissen, one of the world's leading cardiologists, analyzed data from 19 trials on more than 16,000 patients and found Actos actually reduces heart attacks, strokes and deaths by 18%, although it does increase the risk of heart failure.
In the month after May 21, 2007, when the New England Journal of Medicine first published a previous analysis of Avandia studies by Dr Nissen online, that revealed an increased risk of heart attack and cardiovascular death associated with the drug, reports of side effects tripled, according to a July 12, 2007 review of FDA data on adverse events reports obtained by the Associated Press with a FOIA request.
Only five heart attacks were reported in the 35 days before the study appeared online on May 21, 2007, compared with 90 in the same period afterward, and heart-related hospitalizations increased from 11 to 126, the AP found.
From April 16 to May 21, FDA data showed a total of 121 adverse events reported, including 11 deaths. But in the 35 days after the study, 357 events were reported, including 38 deaths.
Avandia was approved on May 25, 1999, and the FDA's primary medical reviewer recommended approval because clinical trials showed it to be effective at reducing blood sugar. But the reviewer also noticed that the data raised questions about Avandia's long-term effect on the heart. An excerpt from the reviewer's findings states:
"Whether [Avandia] favorably affects the natural history of type 2 diabetes is open to question. Long term improvement in HbAl c [a measure of blood sugar] should decrease the risk of retinopathy [eye problems], nephropathy [kidney problems] and neuropathy [nerve problems]."
"However, the increase in body weight and undesirable effects on serum lipids [cholesterol] is cause for concern. Heart disease due to atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes, and it cannot be assumed that treatment with [Avandia] will decrease the risk."
Because of concerns over the possibility for "deleterious long term effects on the heart," the reviewer recommended that "a postmarketing study to address these concerns needs to be a condition of approval."
