May 2007 New England Journal Of Medicine Article Links Avandia to Risk Of Heart Attack, Or Myocardial Infarction

GlaxoSmithKline "Strongly Disagrees" With Idea That Its Diabetes Drug Increases The Risk Of Heart Problems In Diabetics

In their article, "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes", Steven E. Nissen, M.D., and Kathy Wolski, M.P.H., report on a meta-analysis of data from 42 clinical trials that found a 43% increased risk of heart attack among Type 2 diabetics treated with Avandia (rosiglitazon). This Avandia - heart attack article was published online by the New England Journal of Medicine (NEJM) on May 21, 2007; the article will appear in the June 14, 2007 print edition of this leading medical journal.

In a statement posted on the GlaxoSmithKline web site, under the News section, the drug company said it "strongly disagrees with the conclusions reached in the NEJM article, which are based on incomplete evidence and a methodology that the author admits has significant limitations."

For their NEJM Avandia article, Nissen and Wolski -- both with the prominent Cleveland Clinic -- analyzed data from 42 randomized clinical trials which were published on the FDA web site and on a clinical-trials registry maintained by GlaxoSmithKline, the manufacturer of Avandia.

Details of the Avandia Data Analysis Done by Nissen and Wolski:

• All trials had a duration of more than 24 weeks.
• The data were combined by fixed-effects model.
• The mean age of those in the trials was 56 and the mean glycated hemoglobin level was approximately 8.2%.
• Included in the analysis were data from two large trials: (1) the Diabetes Reduction and Assessment with Ramapril; and, (2) Rosiglitazone (DREAM) trial and the A Diabetes Outcome Prevention Trial (ADOPT).

Findings of the Avandia Data Analysis Done by Nissen and Wolski:

• When all small trials were combined, the odds ratio (OR) for myocardial infarction (MI) was 1.45 (95% CI, 0.88-2.39, P=0.15), in DREAM the OR for MI was 1.65 (95% CI, 0.74-3.68 P=0.22), in ADOPT OR for MI was 1.33 (95% CI, 0.80-2.21 P=0.2).
• The overall OR for MI was 1.43 (95% CI 1.03-1.98 P=0.03).
• The OR for death from cardiovascular causes in the 40 combined small trials was 2.40 (95% CI 1.17-4.91 P=0.02).
• In the DREAM trial the OR for cardiovascular mortality was 1.20 (95% CI, 0.52-2.78 P=0.67).
• In the ADOPT trial the OR for cardiovascular mortality was 0.80 (95% CI 0.17-3.86 P=0.67).
  The overall OR for cardiovascular mortality was 1.64 (95% CI, 0.98 to 2.74; P=0.06).

Later the same day of this early release of the NEJM's Avandia article, May 21, 2007, the FDA issued a Safety Alert regarding Avandia which essentially called for the FDA to conduct further study of the data analyzed by Nissen and Wolski in their article.

Read more on our Avandia Information Page >>