TUESDAY, Sept. 11, 2007 (HealthDay News) -- A controversial drug called Avandia, used by millions of diabetics to control blood sugar, greatly increases their risk of heart attack and heart failure, researchers report.
The drug does not up users' overall risk of death, however, the new study finds.
"The balance of risks and benefits has shifted, and this needs to be factored into the equation," said Dr. Sonal Singh, lead author of the study and assistant professor of internal medicine at Wake Forest University School of Medicine in Winston-Salem, N.C.
"The risk of heart failure was known but not the magnitude. A doubling of risk is substantial," Singh added. "One in 30 patients taking rosiglitazone (Avandia) over a year will have heart failure, that's very substantial. And one in 220 will have a heart attack. That's also very substantial." Patients should talk to their doctors about the potential risks and benefits of the drug, Singh said.
The study is published in the Sept. 12 issue of the Journal of the American Medical Association, as does another study, this one finding that Actos (pioglitazone), a diabetes drug in the same class as Avandia, actually reduces the risk of heart attack, stroke and death, even while it increases the risk for serious heart failure.
"This study shows that this drug, used for sugar control, provides an additional benefit of reducing cardiovascular complications," said Dr. A. Michael Lincoff, lead author of the study and vice chairman for research in the department of cardiovascular medicine at the Cleveland Clinic. "This is very strong reassurance."
It's unclear what the new conclusions mean for this class of drugs, called thiazolidinediones. Previous studies have indicated cardiovascular risks, and, in August, the FDA mandated stricter labeling, including "black-box" warnings, for the medications.
"The whole area of thiazolidinediones has been thrown wide open by all these meta-analyses," said Dr. Gregory Dehmer, professor of internal medicine at Texas A&M Health Science Center College of Medicine and director of the cardiology division at Scott & White Hospital in Temple. "For the average clinician in the street, there's a substantial amount of uncertainty, and this is magnified for patients," he said
For the first study, Singh and his colleagues conducted a meta-analysis of four randomized trials of Avandia involving more than 14,000 patients.
In the analysis, Avandia increased the risk of heart attack by 42 percent and doubled the risk of heart failure, similar to findings of a previous study. In this analysis, Avandia did not increase the risk of death from cardiovascular causes, however.
The study received no funding from GlaxoSmithKline, the maker of Avandia.
With an estimated 3.5 million or more U.S. patients taking Avandia, the public health impact could be substantial, the authors point out. This could translate into more than 4,000 excess heart attacks and 9,000 excess heart failure events.
For the second study, also a meta-analysis, Lincoff and his colleagues looked at data from 19 trials involving more than 16,000 participants that looked at Actos and cardiovascular complications.
According to the study authors, Actos' manufacturer, Takeda Pharma, funded the analysis and provided the data from the trials but was not involved in any of the analysis.
Like Avandia, Actos also raised users' risk for heart failure, this time by about 40 percent.
However, unlike Avandia, patients receiving Actos had an 18 percent lower risk of heart attack, stroke or death than patients in the control group.
Why might two drugs in the same class have different effects? "For this type of drug, a 'class' is a really loose term, because the medications have very different actions on multiple targets," Lincoff said. Actos should probably be the first-line choice, over Avandia, he said.
Not surprisingly, Avandia's maker GlaxoSmithKline disputed that conclusion.
The two JAMA studies do not bring any new data forward and "do not confirm a difference in the safety profile of Avandia and Actos," the company said in a statement released late Tuesday.
According to the company, the Actos analysis, in particular, relied heavily on one trial -- the Takeda-funded PROactive study -- which only compared Actos to a placebo. "Patients taking Actos to control blood sugar might be expected to have fewer cardiovascular events than those who were not controlled on medication," the company noted.
GlaxoSmithKline also pointed out that, at this point in time, "no long-term, head-to-head clinical trial data specifically evaluates cardiovascular risk between Avandia and Actos."
Dehmer agreed, saying that more trials, namely randomized trials looking at specifically at cardiovascular outcomes, are needed to fully assess the effects of the two drugs.
For more on diabetes drugs, visit the U.S. Food and Drug Administration.