New Avandia Study Doesn't Prove Safety
Editorial Says Avandia ‘Potentially Dangerous’; GSK Says Study ‘Reassuring’
But editorials published alongside the study paint a far different picture.
The study has several flaws, notes David M. Nathan, MD, director of the diabetes center at Massachusetts General Hospital and professor of medicine at Harvard Medical School in Boston.
"The interim results of the RECORD trial do not provide any assurance of the safety of treatment with [Avandia]," Nathan writes. "Physicians may find it difficult to explain to patients why they are starting treatment with a potentially dangerous drug when other choices with longer and better safety records are available."
The other editorial is by Bruce M. Psaty, MD, PhD, of the University of Washington in Seattle and Curt D. Furberg, MD, PhD, of Wake Forest University in Winston-Salem, N.C. Psaty and Furberg's previous editorial on Avandia questioned the FDA's wisdom in approving the drug.
Now Psaty and Furberg say the very low number of heart disease events in the RECORD trial is suspicious. Coupled with the study's high dropout rate, they suggest this leaves the study without enough statistical power to achieve its goal of proving that Avandia is not inferior in heart safety to standard diabetes drugs.
Moreover, they suggest that when the study findings are combined with data from previous studies, Avandia is still associated with significant risk of heart attack.
"The level of risk, a hazard ratio of 1.33 (a 33% increase in heart attack risk), is substantial and approximately equivalent in magnitude -- but in the opposite direction - to the health benefits of lipid-lowering statin drugs," Psaty and Furberg write.
And an editorial by NEJM Editor Jeffrey M. Drazen, MD, and colleagues, states "even a small increase in cardiovascular risk in a fragile population of patients with type 2 diabetes is of considerable concern.
"There is continued uncertainty about the cardiovascular safety of [Avandia]," Drazen and colleagues conclude.
Krall and Glaxo Vice President of Clinical Development Murray Stewart, FRCP, say that these conclusions distort the RECORD findings.
"It would be very unfortunate if doctors tried to make decisions based on these very small differences between Avandia and standard diabetes drugs," Krall said. "The best interpretation of these findings would be that there are no differences between Avandia and sulfonylurea with metformin."