Avandia and Cardiovascular Safety
by J. Robin Conway, M.D. and Ryan Marble, M.D. Candidate
Published in the Record News EMC August 17, 2007

With the Vioxx fiasco fresh in the hearts of patients and in the scrawling hands of certain members of the media, it comes as no surprise that at the first whiff of controversy the insulin-sensitizer Avandia is in the spotlight. An article was recently published in The New England Journal of Medicine suggesting that Avandia may increase the risk of heart attack by 43 per cent and cardiovascular death by 64 per cent.

Let me assure you that this is not the same situation as what happened in 2004 with Vioxx. There are many facts regarding Avandia that need to be heard and are nowhere to be found in the big bold headlines. The Avandia study has serious limitations, as the study’s authors readily admit. It raises questions, but provides few answers.

First of all, every medical treatment involves weighing the risks against the benefits. Avandia and the class of medications to which it belongs have been a real breakthrough in the treatment of diabetes. Avandia has shown in multiple studies that it lowers blood-glucose levels significantly. Lower blood-glucose levels are associated with a significantly lower risk of eye, kidney and nerve damage, as well as a longer life.

A large research study on type 2 diabetes (the UKPDS) has shown us that diabetes is a progressive disease. All treatments prior to Avandia coming on the market failed because of the progressive deterioration of the pancreas. Avandia was the first drug that showed the potential to slow or possibly stop the deterioration of the function of the pancreas. This was also the first drug of its class in Canada that improved insulin resistance, which is a core defect in type 2 diabetes.

Subsequent research has not only confirmed that Avandia slows pancreatic deterioration but also that it is the most effective treatment that we have to prevent diabetes (the DREAM trial).

The study in the New England Journal of Medicine was what we call a “meta-analysis” which means that it pools the data from many different studies. These individual studies were not conducted with the intention of measuring cardiovascular outcomes and as a result are not standardized. It would seem logical to have a very large study that was conducted to evaluate cardiovascular outcomes specifically so that we could answer the question with a high degree of certainty. Such a study does exist and is currently in progress.

This study, the RECORD trial, was designed specifically to assess cardiovascular outcomes associated with Avandia. Since the media firestorm has spread, fear has reigned supreme and many of the study’s participants are dropping out. Interim results from the study were analyzed and did not show a significant increase in cardiovascular risk, although more time is needed to verify this. It is a real possibility that there will not be enough data to provide a definitive answer on the cardiovascular safety of Avandia. It is ironic that the study that raised the concerning question will perhaps indirectly lead to that very question not being answered.

In other major, well-controlled studies of Avandia, there has been no associated increase in risk of heart attack. A study done on another member of the same class of medication (Pro-Active Study) using Actos suggested a reduction in cardiac events in people taking the drug. Patients can also find it reassuring that on July 31, 2007 an expert committee reporting to the FDA voted 22-1 to keep Avandia on the market.

In the mean time, it would be prudent for patients to discuss Avandia with their doctor before unduly discontinuing it. For further information regarding Avandia or any other diabetes-related questions, please visit our website at www.diabetesclinic.ca.