Revisiting the Avandia Scare: Results from the RECORD Trial
A few years ago, Dr. Steven Nissen and Dr. Kathy Wolski of the Cleveland Clinic published an analysis of several clinical studies that stirred controversy regarding the cardiovascular safety (risk of heart disease) of Avandia, also known as rosiglitazone (for our coverage of the issue, see Learning Curve from diaTribe #6). Avandia belongs to the thiazolidinedione (TZD) class of drugs for the treatment of type 2 diabetes. Currently, only two TZDs are available in the US and Europe, Avandia and Actos (pioglitazone). Dr. Nissen’s study reviewed data from 42 clinical trials of Avandia to conclude that there is a significant increase in cardiovascular risk following the use of Avandia compared to people who did not take Avandia – setting the mainstream media ablaze. However, many statisticians and physicians vehemently disagreed with the methods and conclusions of the study. We were particularly struck by the attention this study attracted from the media, given the numerous concerns about the validity of the study. Since then, skeptics as well as supporters of Dr. Nissen’s analysis have eagerly awaited the results of a five-year clinical study, RECORD, to validate their respective hypotheses. The RECORD trial evaluated the cardiovascular risk of Avandia in nearly 4,500 individuals and the results were finally presented to an overflowing crowd at this year’s annual meeting of the American Diabetes Association. It found that patients taking Avandia had no overall increased cardiovascular risk compared to those taking metformin or a sulfonylurea. These results clearly refuted Dr. Nissen’s study and reinforced the FDA’s initial decision to approve the drug for individuals with type 2 diabetes. However, it should be noted that results did confirm increased risk of heart failure and bone fractures (particularly in women), suggested previously as class effects for the TZDs – thus, the presenters suggested Avandia should not be recommended for people with a history of heart failure and should be used with caution in women at a high risk for bone fractures. As a side note, Dr. Nissen also conducted a similar review of Actos studies and found no association with increased cardiovascular risk; in fact, some studies have indicated Actos may demonstrate a protective effect on the heart.