Study Links Diabetes Drug To Heart Attack Risk And Death, FDA Alerts

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Main Category: Diabetes
Also Included In: Cardiovascular / Cardiology;  Clinical Trials / Drug Trials;  Public Health
Article Date: 22 May 2007 - 0:00 PST

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A recent US study has linked the diabetes type 2 drug rosiglitazone (brand name Avandia) to increased risk of heart attack and cardiovascular death and has led to the Food and Drug Administration (FDA) issuing a safety alert to doctors to be aware of the findings.

The study is published in the current issue of the New England Journal of Medicine.

The FDA are not saying that patients should stop taking the drug since other trials "provide contradictory evidence about the risks in patients treated with Avandia". The agency says it is not yet in a position to say what clinical significance this new reported increased risk has in the context of other studies, some of which are not yet completed.

Concerned patients should speak to their doctor about this new information, said the FDA. Their doctor can evaluate the treatment options for their particular situation. And not to be forgotten is that sometimes switching treatments introduces an extra risk of its own.

Chairman of Cardiovascular Medicine at the Cleveland Clinic in Ohio, US, Dr Steven Nissen and Cleveland Clinic statistician Kathy Wolski, analysed the data on 42 randomized controlled trials lasting more than 24 weeks and found that rosiglitazone raised patients' heart attack risk by 43 per cent and their risk of cardiovascular death by 64 per cent compared to placebo or other therapies.

The researchers said that until now, although rosiglitazone is widely used to treat patients with type 2 diabetes mellitus, its effect on cardiovascular disease and death has not been determined.

These findings raise a potential public health concern because more than 65 per cent of deaths among diabetic patients are heart disease related.

Nissen and Wolski included all the studies they could find that met their meta-analysis criteria which included: duration more than 24 weeks, control group not receiving the target drug, availability of outcome data including incidence of heart attack and cardiovascular death.

They looked in published literature, the FDA website and the registry of the drug manufacturer GlaxoSmithKline (GSK) and found 116 studies of which 42 met the inclusion criteria.

The 42 studies covered 15,560 patients who were randomized to regimens including rosiglitazone and 12,283 to comparator groups that did not.

The results showed that in the 42 trials:

• The mean age of the participants was 56 years.
• There was a moderate male predominance (53 to 61 per cent).
• The mean baseline glycated hemoglobin level was approximately 8.2 per cent.
• Compared with the control group (placebo or other diabetes drug), the rosiglitazone group had a 43 per cent greater risk of myocardial infarction (heart attack).
• Also, compared with the control group, the rosiglitazone group had a 64 per cent greater risk of death from cardiovascular causes.

Nissen and Wolski concluded that:

"Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance."

They also pointed to the study's limitations, which included "Lack of access to original source data, which would have enabled time-to-event analysis".

However, despite these limitations, they said:

"Patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes."

Glycated hemoglobin is a measure of how well diabetes is being controlled. Hemoglobin is found in red blood cells and carries oxygen, and over time, as the cells are exposed to high levels of sugar or glucose in the blood, the hemoglobin absorbs the glucose, it becomes "glycated".

The range for a healthy person is around 4 to 6 per cent. According to WebMD, the accepted goal for a person with diabetes is to control their glycated hemoglobin to around 7 per cent.

The FDA approved rosiglitazone for use in diabetes in 1999, based on the drug's ability to lower blood glucose and reduce glycated hemoglobin. Since then, the drug has been prescribed about 60 million times and is being used by several million American diabetics.

"However, the objective of lowering blood sugar is the reduction of the complications of diabetes," Dr. Nissen explained in a prepared statement.

"The effect of anti-diabetic therapy on cardiovascular outcomes is of critical importance because cardiovascular disease represents the overwhelming source of diabetic mortality. Unfortunately, rosiglitazone appears to increase, rather than decrease, the most serious complication of diabetes, heart disease," he added.

"Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes.
Nissen, Steven E and Wolski, Kathy.
Engl J Med 2007 0: NEJMoa072761.
Published online May 21, 2007 (10.1056/NEJMoa072761).

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Written by: Catharine Paddock
Writer: Medical News Today


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