Avandia Fails In Atherosclerotic Plaque Study

GlaxoSmithKline’s diabetes drug Avandia (rosiglitazone) has failed to show it can significantly reduce atherosclerosis in patients with type 2 diabetes.

While study results, presented at the American Heart Association scientific meeting, last week, demonstrated the endpoint did not reach statistical significance, the drug giant is maintaining it is “encouraged” by the findings suggesting that treatment with Avandia “may stall the progression of coronary atherosclerosis”.

“This study supports but does not prove the hypothesis that rosiglitazone has greater anti-atherosclerotic effect than glipizide in patients with type 2 diabetes,” said lead study investigator Dr Richard Nesto.

The study, called APPROACH, compared the reduction of atherosclerotic plaque volume between Avandia and sulfonylurea glipizide, marketed by Pfizer as Glucotrol.

Results from the 18-month 672-patient study found patients who took Avandia achieved a 0.21% reduction in atherosclerotic plaque, while patients taking glipizide achieved a 0.43% increase. In terms of safety, there were no unexpected differences between Avandia and glipizide, GSK said.

However, Avandia was found to be statistically significantly better that glipizide in measures of total volume of blood vessel blockage and fewer low blood sugar incidents.
The study is not good news for GSK, as Avandia has failed to produce positive results in a number of clinical trials and has even been linked to an increased risk of heart attack.

While Avandia patients didn’t worsen in the trial, the findings probably won’t ease doctors’ safety concerns, said Steven Nissen, head of cardiology at the Cleveland Clinic in Ohio.

“The Approach trial was too small to confirm or refute the safety issues previously raised for rosiglitazone,” said Nissen, who conducted the study that uncovered the initial concerns with Avandia. “The failure of the Approach trial provides one more reason to use rosiglitazone with caution.”

The Approach study peered inside the arteries of 672 patients with diabetes using a procedure known as intravascular ultrasound that measures plaque buildup.
In the study, those on Avandia had higher cholesterol levels, lower blood pressure, and less inflammation.

“This adds real data to a controversy over the past year,” said Nesto, the lead author and an associate professor of cardiovascular medicine at Lahey Clinic in Burlington, Mass.. “It’s reassuring that there is no direct effect on the coronary arteries that one would consider adverse. We can safely say the drug does not increase atherosclerosis.” 

The study reported last week at the American Heart Association meeting in New Orleans.