FRIDAY, June 5, 2009 (HealthDay News) -- The diabetes drug Avandia significantly raises the risk of both heart failure and bone fractures, but it does not boost the odds for either cardiovascular disease or death, new research has found.
If anything, the drug may slightly lower the overall risk of death, said the authors of the much-anticipated RECORD study, which was presented Friday at the American Diabetes Association's annual meeting in New Orleans and published simultaneously online in The Lancet.
"The findings essentially are that, in overall cardiovascular terms, the drug is safe," Dr. Philip D. Home, chairman of the study steering committee and a professor of diabetes medicine at Newcastle University in Britain, said during a Friday news conference. "There's no decreased risk, and that includes the heart failure element. If anything, deaths were reduced with rosiglitazone [Avandia] compared to those in the control group. It doesn't reach statistical significance, but it's on the right side of benefit."
The trial was funded by GlaxoSmithKline, which makes Avandia.
Home stated that the drug "clearly has a role, alongside other drugs [in the treatment of diabetes], provided you obey the contraindications, which are not to use it in people with heart failure and to think twice for people at high risk for fractures."
Dr. Carl J. Lavie, medical director of cardiac rehabilitation at Ochsner Heart and Vascular Institute in New Orleans, said, "This study provides some degree of support that Avandia is probably not adversely affecting cardiovascular health to any major degree."
But Lavie added that many physicians are waiting for the results of another trial, known as TIDE, which compares Avandia with Actos, another drug in the same class. "Until then, I suspect that not much will change -- both drugs are contraindicated in heart failure and I doubt that this trial will lead the societies to change their recommendations that were based on many trials," he said.
And the findings are unlikely to quell an ongoing controversy about the safety of the drug, which was further fueled by a 2007 meta-analysis reporting a heightened risk of heart attacks with Avandia.
Although Home called that meta-analysis "weak," Dr. Steven Nissen, co-author of the 2007 paper and chairman of the department of cardiovascular medicine at the Cleveland Clinic, stated that the RECORD trial was "seriously flawed," citing the fact that more patients in the Avandia group were taking cholesterol-lowering statins and that group had what looked to be a high drop-out rate.
"Obviously, it is impossible to assess the safety of a drug when patients are not actually taking it," he said.
Avandia, one of a class of medications known as thiazolidinediones, is used to lower blood sugar in patients with type 2 diabetes in combination with two other drugs, metformin and sulfonylurea.
Several earlier studies had suggested that the risk for heart failure, death and heart attack was increased with Avandia, touching off a controversy that resulted in new U.S. Food and Drug Administration-mandated label warnings about the drug.
In 2008, the advocacy group Public Citizen called for a ban on the drug, just as an American Diabetes Association/European Association for the Study of Diabetes working group unanimously advised against the use of the drug.
Presented Friday at the ADA meeting were the final results of the RECORD trial, which involved 4,447 patients with type 2 diabetes, randomly selected to take Avandia plus metformin and sulfonylurea or just metformin and sulfonylurea.
"There was better persistence of glucose control over a course of five years, an approximate doubling in heart failure and a probability that it increased death from heart failure but that is within the context of, if anything, less death and no increase in overall cardiovascular disease," Home said. "Something is balancing it out, and it may well be the reduction in the risk of stroke."
The heart attack data was not conclusive, although the fracture rate, at least in women, was significantly higher among those taking Avandia.
Recommendations issued earlier this year had removed Avandia from the list of drugs doctors should consider using, Dr. David Nathan, chairman of the consensus committee that released that document, said during the news conference. "I think we will take this data back to our committee and discuss it. We will go back and reconsider."
Even if doctors decide to try prescribing the drug again (its usage dropped in large numbers after the 2007 meta-analysis by Nissen), figuring out which patients with type 2 diabetes shouldn't be taking Avandia may be difficult, said Dr. Suzanne Steinbaum, director of women and heart disease at Lenox Hill Hospital in New York City.
"These patients are already at risk for heart disease. How do you select or omit patients because they are all at risk for heart disease because of their diabetes? Heart failure and fractures are processes that we are already trying to prevent in this population."
Find out more about type 2 diabetes at the American Diabetes Association.