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Patients shouldn't stop use abruptly

But other drugs offer safe history

A popular diabetes drug appears to increase the risk of having a heart attack, according to a report published online yesterday by the New England Journal of Medicine . Patients who took the drug, known as rosiglitazone or Avandia , were 43 percent more likely to have a heart attack than those who took other drugs or a dummy pill, studies found.

This impact is particularly troubling for diabetics, who are at high risk of heart disease anyway if they are unable to control their blood sugar.

However, the report is by no means the last word on the subject. The authors, from the prestigious Cleveland Clinic , note that their findings are suggestive, rather than conclusive. GlaxoSmithKline , the pharmaceutical giant that manufacturers the drug, is defending its safety.

Following is some additional information to help patients and doctors sort out the implications.

Q. How strong is the evidence?

A. Not terribly strong. While the link with heart attacks was statistically significant, not likely to be caused by chance, it was based on a small number of heart attacks because the studies did not follow patients very long. The report also found a weaker link -- that could be due to chance -- with death from heart attack. The authors said their efforts to get to the truth were hindered by not having access to the raw data behind the 42 short studies on which they based their findings. Nonetheless, because "the risk is heart disease -- heart attacks and death from heart attacks -- you have to take this seriously," said Dr. David Nathan , of the Diabetes Center at Massachusetts General Hospital, who was not involved with the research.

Q. Is there other evidence of heart problems with Avandia?

A. Yes. Studies have shown that the drug can increase the risk of congestive heart failure, a condition in which the heart must work very hard to pump blood. Last year, the FDA added a warning to the drug about a possible increased risk of heart attacks in patients with congestive heart failure. Dr. Sidney Wolfe , of the advocacy group Public Citizen, said yesterday that there have been 689 cases of heart failure among patients on Avandia reported to the FDA since 1999, when the drug was first sold.

The FDA said yesterday that there are other unpublished, long-term studies of Avandia that contradict the new study's findings.

Q. What should patients do?

A. Patients taking Avandia should not abruptly stop the drug, the FDA said. Instead, they should meet with their doctors to discuss their risk of a heart attack and how well their diabetes is controlled, according to Dr. Larry C. Deeb , president of medicine and science for the American Diabetes Association. "The doctor needs to take a close look at why they put the patient on rosiglitazone and does the risk justify taking them off. The drug seems to help with blood sugar control. But if you have diabetes, you have the heart disease risk of someone who already had a heart attack."

Q. Are there other diabetes drugs that do not affect the heart?

A. Yes. Metformin and insulin are two that have been used safely for years, according to Dr. Nathan. "There are nine classes of diabetes drugs," he said. "No one should be trapped into using any single drug." One study, which Nathan said used flawed methodology, suggested that a sister drug to Avandia called Actos might protect against heart disease.

Q. What might cause the drug to harm the heart?

A. The drug is known to increase "bad" cholesterol levels in patients. It also can increase stress on the heart, the authors of the report suggested, by causing congestive heart failure. But the exact mechanism of any possible harmful effect is not known.

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