Avandia Raises Heart Failure Risk More Than Actos

TUESDAY Aug. 18, 2009 -- The type 2 diabetes drug Avandia (rosiglitazone) increases the risk of heart failure and death more than another drug in the same class, Actos (pioglitazone), new Canadian research contends.

Avandia has been the subject of controversy since 2007, when it was linked to an increased risk for heart attack and death, although those claims have become clouded as other studies have discounted that risk to some degree. But taken together, many believe that the drug should not be used, especially since there appears to be a safer choice.

"It is difficult for making a case for using rosiglitazone in anybody, because we have an alternative," said lead researcher Dr. David Juurlink, division head of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto.

In 2007, Dr. Steven Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, published a study that found Avandia showed a 43 percent greater risk of heart attack among diabetes patients, and he remains convinced that the drug should not be used.

"I agree with the authors' conclusions," Nissen said. "Rosiglitazone should not be used in patients with diabetes. Pioglitazone is a safer alternative."

There is increasing evidence that Actos is safer than Avandia, Juurlink said. "Not a single study has suggested that pioglitazone might be less safe than rosiglitazone," he said. "And rosiglitazone doesn't have a single advantage -- not even a theoretical one."

Both Avandia and Actos belong to a class of drugs called thiazolidinediones, which are used widely to lower blood sugar in people with type 2 diabetes. In addition to an increased risk for heart failure, both drugs can also cause side effects that include weight gain and fluid retention. Both medications carry a U.S. Food and Drug Administration warning label about the risk of heart failure and heart attack.

The latest report on the safety of these drugs is published online Aug. 19 in the BMJ.

For the study, Juurlink's team collected data on 39,736 patients treated with Avandia or Actos between April 2002 and March 2008. The researchers compared these data with hospital records of heart failure, heart attack and deaths.

The researchers found that patients taking Avandia were at greater risk of heart failure and death than those taking Actos. There was no significant difference between the drugs for the risk of heart attack, Juurlink's group noted.

For every 93 patients treated with Avandia instead of Actos, there was one additional cardiovascular event or death per year, the researchers estimated.

"As a clinician, I cannot envision an instance in which I would recommend rosiglitazone," Juurlink said.

However, Corinne de Vries, a professor of pharmacoepidemiology in the department of pharmacy and pharmacology at the University of Bath, England, and co-author of an accompanying journal editorial, is not convinced that Avandia is less safe than Actos.

"Nobody should stop taking their medication without consulting their doctor, because I don't think rosiglitazone kills you," de Vries said.

De Vries said the conclusions of this study are not supported by the data Juurlink's group used. People taking Avandia were sicker than those taking Actos, so these patients were more likely to develop heart failure, she noted.

"The data presented by Juurlink do not support the suggestion that you should favor one drug over the other," de Vries said. "There is no reason to believe yet that there is a difference."

People who have a preexisting heart condition should not be started on either of these drugs, de Vries stressed. Patients who develop heart failure should have the drug discontinued, because the condition is usually reversible, she added.

Another expert, Dr. Carl J. Lavie, medical director for cardiac rehabilitation and prevention director of the Stress Testing Laboratory at the Ochsner Heart and Vascular Institute in New Orleans, thinks the study gives more reasons not to use Avandia.

"I believe that most clinicians have stopped using Avandia -- some will use Actos instead or go to another class completely," Lavie said.

Lavie noted that an ongoing study assessing Avandia and Actos in a head-to-head comparison should provide more answers about these drugs.

"Until then, this current study provides further ammunition against using Avandia or at least for trying Actos first, which is along the same lines as the current American Diabetes Association and European guidelines anyway," Lavie said. "Most will, and should, avoid either agent in a patient with heart failure or high heart failure risk."

"Both drugs have a place in treating diabetes, but not if you have a preexisting heart condition," de Vries said.

More information

For more information on diabetes, visit the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Posted: August 2009


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