I recently described a report of a meta-analysis which concluded that rosiglitazone (Avandia®) was associated with a 43 percent increased risk of a heart attack. This report, which appeared in the New England Journal of Medicine, has resulted in Congress planning to hold hearings on the safety of the drug.
In addition, the Food and Drug Administration (FDA) will convene a panel to review Avandia's safety. Meanwhile, the FDA has issued a "black box" warning not only for Avandia but also on the other thiazolidinedione Actos (pioglitazone). New prescriptions for Avandia have already taken a dive due to the concerns of doctors and patients alike.
The New England Journal of Medicine has now published the results of another trial on the safety of Avandia, along with three new editorials on the subject.
Ironically, this new trial (the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes, or RECORD, trial) was originally designed to evaluate the cardioprotective effect of rosiglitazone over a 6-year follow-up period. The possibility of increased heart attacks, however, has led the steering committee of the RECORD trial to undertake an unplanned interim analysis of some cardiovascular end points in the 2,220 patients taking rosiglitazone during the first 3.75 years of RECORD's follow-up.
The results of RECORD's interim analysis did show a trend toward an 11 percent increase in cardiovascular events in those taking rosiglitazone; these findings, however, are considered inconclusive because they did not reach statistical significance.
While the full 6-year follow-up may or may not conclusively show an increased risk, there is a good chance that the issue will not be resolved even after completion of the trial. It certainly does appear highly unlikely, though, that the drug will be shown to provide protection against heart attacks.
The interim analysis of the RECORD trial did show a doubling of the risk of heart failure in those taking rosiglitazone, similar to the findings of earlier studies. While the results from a well-designed clinical trial are usually more reliable than results from a meta-analysis, the interim findings from the RECORD trial do not have the statistical power to resolve the issue.
In one editorial, Dr. David Nathan from the Diabetes Center at Massachusetts General Hospital stated that "the interim results of the RECORD trial do not provide any assurance of the safety of treatment with rosiglitazone," and he went on to say that the evidence for a heightened danger of cardiovascular disease "must be taken seriously."
Nathan finally added, "Physicians may find it difficult to explain to their patients why they are starting treatment with a potentially dangerous drug when other choices with longer and better safety records are available."
