Two Diabetes Drugs Double Heart Failure Risk: Study

FRIDAY July 27, 2007 -- Patients taking either of the diabetes drugs Avandia or Actos face twice the risk of developing heart failure compared to people not on the popular medications, a new study finds.

This means for every 50 patients with type 2 diabetes taking these drugs, one patient will develop heart failure within 26 months, according to the report released Friday and published in the August issue of Diabetes Care.

"Both Avandia and Actos double the risk of heart failure," concluded the lead author of the first study, Dr. Sonal Singh, an assistant professor of internal medicine at Wake Forest University School of Medicine. "We know these drugs increase the risk, but we found the risk is more substantial than suspected. This occurs at even the lowest dose and among young patients."

The report follows a U.S. government review released Thursday that found Avandia's heart risks are far higher than Actos'. That report sets the stage for an advisory panel hearing Monday that will examine whether Avandia's cardiovascular risks warrant a stronger warning label.

Avandia (rosiglitazone) and Actos (pioglitazone) are from the same family of diabetes drugs and used by more than 3 million diabetic patients across the United States.

The current product label warns against using these drugs in patients with more severe cases of heart failure. The label also warns that there is an increased risk of heart failure if the drugs are used in combination with insulin.

Singh's group, however, found that the risk wasn't limited to patients on insulin, and it was present even among patients without any risk factors for heart failure.

The government study, by a medical and safety review team at the Food and Drug Administration, found that patients are at much higher risk of heart problems if they take Avandia, compared to patients taking Actos. Avandia is especially hazardous to patients who are already on insulin, the report found, whereas Actos users can take insulin as well without fearing cardiac side effects, the New York Times reported.

That data could help decide whether or not Avandia remains on drug store shelves, experts said.

"A critical question to be resolved in determining appropriate regulatory action is whether the anticipated therapeutic benefit of rosiglitazone outweighs the demonstrated cardiovascular risk," one FDA reviewer concluded according to the Times report.

In the Diabetes Care study, Singh's team collected data on more than 78,000 patients taking either of the drugs. These patients were included in previously published studies and in case reports.

Not only did the drugs double the risk of heart failure, but the increased risk was seen with both high and low doses, the team found.

Heart failure developed in some patients taking lower doses than are commonly prescribed. The average time for heart failure to develop was 24 weeks after starting the drugs, the researchers found.

Heart failure wasn't confined to older patients. Twenty-five percent of the patients who developed heart failure were under 60. In addition, both men and women developed heart failure while taking the drugs, Singh noted.

Singh's group suspect that Avandia and Actos may boost heart failure risk by encouraging fluid retention.

Current guidelines allow the use of these drugs in patients with early-stage heart failure. "Based on our information, that may have to change," Singh said.

Singh noted that there are alternative drugs available. "Doctors should be aware of the risk," he said. "Patients who are on these drugs and start developing symptoms of heart failure should see their doctor immediately, and patients not on these drugs should look at alternatives."

One expert believes that patients taking Avandia and Actos face not only an increased risk of heart failure, but Avandia users also face a 43 percent increased risk of heart attack.

"This hazard of heart failure is pretty well known for these drugs," said Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic. He noted that, in May, the FDA said it was going to mandate a "black box" warning about heart failure risk on the labels of these drugs.

That same month, Nissen published a paper in the New England Journal of Medicine that found that Avandia increased the risk of heart attack.

Since then, the controversy has continued, with both sides weighing in.

On Thursday, Mary Anne Rhyne, a spokeswoman for GlaxoSmithKline, which makes Avandia, responded to the new government review by saying the company continued to believe Avandia was safe, the Times reported.

"Across the extensive data we have, the science shows no increase in cardiovascular death, and does not support a difference in heart attack rates between Avandia and the other most commonly prescribed oral antidiabetics," Rhyne told the Times.

On Friday, the company's director of clinical development, Dr. Andy Zambanini, told HealthDay that Glaxo was "still in negotiation with the FDA about a new warning label on heart failure, and we expect to release that information soon."

Nissen believes that patients who are considering taking Avandia should discuss the decision with their doctor. "It is important that the totality of information be out there," he said. "But no patient should stop taking a medication [only] because they read a news report."

Another expert contends that the two drugs are safe if prescribed correctly.

"The risk for heart failure with these drugs may be one in 50, but if you can correctly identify who that person [at risk] is, you can safely treat the other 49 and not hurt anybody," said Dr. Larry Deeb, president for medicine and science at the American Diabetes Association.

Deeb believes the same holds true for the risk of heart attack.

The boost in risk of heart failure and heart attack does not warrant taking these drugs off the market, he added.

"They fit into the armamentarium of diabetes drugs if used properly," Deeb said.

More information

Learn more about diabetes drugs from the U.S. Food and Drug Administration.

Posted: July 2007


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