Avandia, a controversial but popular drug used to control diabetes, increases the risk of heart attack, stroke, heart failure and death, researchers reported today in a study published in the Journal of the American Medical Association.
Researchers who carried out the JAMA study estimate the drug caused 48,000 heart attacks, strokes and heart failures in patients over age 65 from the time it was introduced in 1999 until June 2009. The research was funded by the Centers for Medicare & Medicaid Services and by the U.S. Food and Drug Administration.
Since 2007, several studies have questioned the safety of the drug, prompting the FDA to require a black-box warning with all new prescriptions.
Sales of the drug have fallen sharply, but some researchers say failure to completely ban the medication calls into question the FDA’s drug safety process.
By leaving Avandia on the market, “the FDA has basically allowed many thousands of additional patients to be injured or killed with no prospect of unique benefit,” says researcher David Graham, M.D., of the FDA’s Center for Drug Evaluation and Research, who says he is not speaking for the agency.
The drug’s manufacturer, GlaxoSmithKline, says the studies have been inconclusive. The FDA has set a review of the drug’s safety for July 13 and 14.
The JAMA study evaluated 227,571 people on Medicare who took either Avandia (rosiglitazone) or Actos (pioglitazone). It found that, compared with Actos, Avandia had an increased risk of heart failure, stroke and death.
Moreover, Graham says, while Avandia carries increased risks, it is no better than Actos for treating blood sugar problems.
No benefit, increased risk
A separate analysis of 56 clinical trials involving some 35,000 patients—published today in the Archives of Internal Medicine—found that Avandia boosts heart attack, stroke and death by 28 to 39 percent. That study, led by cardiologist Steven Nissen, M.D., of the Cleveland Clinic, is a follow-up to one he conducted in 2007 that found the drug may increase the risk of dying from a heart attack or stroke by as much as 64 percent.
“I said it in 2007. I will say it again. This drug has no unique benefits. It increases risk of very serious consequences, and I believe that it should be removed from the market,” Nissen says.
Nissen calls Graham’s research “a powerful study” and says the two studies, done independently, without funding from any drug companies, have both found the drug carries heart risks.
David Nathan, M.D., professor of medicine at Harvard Medical School, heads a panel of experts convened by the American Diabetes Association to recommend guidelines for treatments of the disease.
He says the group recommended in 2008 that doctors prescribe Actos rather than Avandia when first-line drugs such as metformin didn’t control blood sugar. The American Diabetes Association did not endorse those guidelines.
Because glucose-lowering drugs are aimed primarily at reducing serious diabetes complications to the eyes, kidneys and nerves, drugs like Avandia are “incredibly important,” he explains.
On the other hand, Nathan says, because heart disease is the main killer of diabetics, there’s no reason to use a drug that increases risk of heart problems when other drugs are available.
Although he says the risks of Avandia aren’t absolutely proven, he thinks that the evidence is good enough that he doesn’t prescribe it.
Mary Anne Rhyne, a spokesperson for GlaxoSmithKline, says that previous randomized clinical trials—the gold standard for medical research—found that Avandia does not increase the overall risk of heart attack, stroke or death, and that an analysis of 52 clinical trials conducted by the company found the drug does not interfere with blood flow to the heart.
Neither of the two new studies explained why the drug might cause heart problems.