DOCTOR'S VIEW ARCHIVE
Medical Author: Ruchi Mathur, MD, FRCP(C)
Medical Editor: Melissa Conrad Stöppler, MD
Steven Nissan and colleagues released an article in the New England Journal of Medicine recently that reviewed the relationship between rosiglitazone (Avandia) and the risk of heart attack and death from cardiovascular causes. Rosiglitazone is one drug in a class of insulin sensitizers known as thiazolidinediones, or TZDs. This class of drugs is commonly prescribed for the treatment of type 2 diabetes and for insulin resistance. The authors of the recent paper reviewed 42 published and unpublished randomized clinical trials, studying patients taking rosiglitazone for a minimum of 24 weeks. Their analysis found a significantly increased risk for heart attack and an even higher risk for overall cardiovascular death from all causes.
While this is of concern, it is important to realize these data were analyzed in a retrospective fashion (looking back at what has happened) as opposed to looking forward with a single study designed to look for the effects of rosiglitazone specifically on the heart as patients continue using the drug into the future. Retrospective studies have inherent flaws in them,, which must be stated and taken into account when the data are reviewed. However, the numbers in the study are convincing, and when translated into "real numbers," there were 86 heart attacks in the rosiglitazone group and 72 in the control group. There were 39 deaths from cardiovascular causes in the rosiglitazone group compared with 22 in the control group.
Is this an effect of this class of drugs? At present, we don't think so. Recent large studies have found that the other drug in same class as rosiglitazone - called pioglitazone (or Actos) may be beneficial in heart disease. The major difference may be in the effects on the blood cholesterol profile between these two drugs. Rosiglitazone is associated with a worse blood cholesterol profile when compared to pioglitazone. Both drugs can cause fluid retention, which can be a problem in patients with congestive heart failure, and should be avoided in patients who have this condition.
What should you do if you are taking rosiglitazone? First, don't panic. Second - speak with your primary provider about your options. Remember that TZDs do help in blood sugar control and there are advantages to being on a TZD. Together with your provider, you should discuss the best plan of action for your particular situation.
As an addendum to this perspective, the FDA has asked the makers of Avandia to add a boxed warning (their strongest form of warning) to their package insert on Novemeber 14, 2007. The FDA cites the above data and stating that based on the above data, Avandia is associated with an increased risk of angina or myocardial infarct (heart attack). The warning is a reasonable approach until further prospective data is available to define the absolute risks.
Reference: Nissen, S.E. and Wolski, K. The New England Journal of Medicine, early release, May 21, 2007.