New Study Shows Older Diabetics Were More Likely To Develop Heart Failure Or Die When Using Avandia As Opposed To Actos
(Posted by Tom Lamb at DrugInjuryWatch.com)
UPDATE: Avandia Should Be Removed from the Market, Some FDA Staff Advise
- January 2010 Senate Committee on Finance report on Avandia (Free PDF)
- February 19, 2010 New York Times story (Free)
- February 20, 2010 GlaxoSmithKline news release on Senate report (Free PDF)
- February 20, 2010 GlaxoSmithKline news release on Times story (Free PDF)
In late November 2008 the medical journal Archives of Internal Medicine published an article about a study that found patients aged 65 and older who were taking Avandia (rosiglitazone) had a 15 percent higher rate of death and a 13 percent greater risk of heart failure when compared with similar patients taking (pioglitazone). Both of these diabetes drugs are part of a class of drugs called thiazolidinediones.
As you may recall, the controversy over whether there are increased heart risks caused by Avandia began with a 2007 study by Steven E. Nissen, M.D., and Kathy Wolski, M.P.H., that was published in the New England Journal of Medicine and which reported a 43 percent increased risk of heart attack among patients taking Avandia.
The more recent Archives of Internal Medicine article, "Comparison of Cardiovascular Outcomes in Elderly Patients With Diabetes Who Initiated Rosiglitazone vs Pioglitazone Therapy", seemingly renewed this controversy and certainly produced a mix of reactions in the days following its publication.
We begin with some comments from Dr. Wolfgang C. Winkelmayer, one of the authors, who explains the impetus for his study in a November 24, 2009 Reuters article, "Safety risks higher with Avandia than Actos - study":
Recent analyses of clinical studies found Avandia raised the risk of heart attacks, which has sent sales of the drug plummeting. An analysis of studies on Actos, meanwhile, suggested it reduced the risk of heart attacks and strokes....
"Altogether, the picture people got was it looks like rosiglitazone might be associated with badness and pioglitazone is neutral and even beneficial," Winkelmayer said in a telephone interview.
"For me, that left an important question open. What if you happen to directly compare those two treatments together," Winkelmayer said in a telephone interview....
Winkelmayer said the study was not a randomized clinical trial, which is the most reliable type of study, but he said the characteristics in both study populations were surprisingly similar, making the comparison quite strong.
"I think it's one more piece of the puzzle," he said.
"It will contribute to a more compelling picture that will inform policymakers with regard to how to move forward."
From a November 25 New York Times article, "Diabetes Drug Linked to Higher Risk of Death", we get these two rather divergent viewpoints:
Dr. John Buse, chief of endocrinology at the University of North Carolina School of Medicine and president of the American Diabetes Association, said the new study is important but limited.
“This is about the tenth report suggesting that rosiglitazone is associated with excess cardiovascular problems,” he said. “We don’t have proof yet.”...
Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, said he hoped this study would be “the last nail in the coffin of this drug.”
“The big attraction of these drugs is that they are insulin-sensitizing drugs and forestall the time when someone would have to go on to insulin,” Dr. Wolfe added. “But with a 15 percent excess mortality over even pioglitazone, which itself is dangerous, that doesn’t seem like a very good tradeoff.”
A November 24 HealthDay article, "Avandia's Heart Risk Higher Than Others in Its Class", included parts of the statement issued by GlaxoSmithKline -- the drug company that makes of Avandia -- concerning the Avandia vs. Actos study article by Dr. Winkelmayer and his colleagues:
The company "strongly supports the safety and efficacy of Avandia based on extensive clinical trial experience and widespread post-marketing use. This new study is inconsistent with evidence from randomized clinical trials and has significant limitations," the statement said.
A randomized clinical trial -- in which participants are randomly grouped and then followed prospectively over time -- is typically considered more reliable than an observational study, which is not as well-controlled.
"The primary outcome in this observational analysis is all-cause mortality," the company statement added. "The Avandia prescribing information includes data from RECORD, an ongoing long-term randomized clinical trial that has shown no statistically significant differences between the Avandia group and the control group regarding death from cardiovascular causes or any cause."
In that same HealthDay article, Eric J. Topol, M.D., offers an observation that serves to concisely sum-up the situation:
"The study reinforces the heart failure risk of rosiglitazone versus pioglitazone," Topol said. "Interestingly, it doesn't show any difference in heart attack, which is the one issue that has been so controversial. So it doesn't really change things that much."
Of the two drugs, Actos appears to have a more favorable track record, Topol added. "But the possibility of cardiovascular side effects, including heart failure and heart attack, can't be forgotten."
We will continue to monitor the medical journals for new reports about the safety profiles of Avandia and Actos.