Putting the RECORD straight?

Ever since the withdrawal of troglitazone, questions had been raised about the safety of the thiazolinediones, rosiglitazone and pioglitazone, which were available for clinical use with special emphasis on their safety in terms of cardiovascular morbidities and mortality. Even though the U.S. FDA was looking into this matter and had advised a black box warning about the cardiovascular safety of rosiglitazone, a meta-analysis published in 2007 by Nissen et al in the NEJM brought things to a head, by showing a significant increase in the risks for cardiovascular morbidity as well as morbidity with the use of rosiglitazone. It also refuted the possibility that this may be a class effect by showing the relative safety of pioglitazone. Home et al reported an interim analysis of their RECORD study which refuted many of the findings of the meta-analysis published by Nissen et al. In spite of the accepted shortcomings of the meta-analysis as well as the significant questions raised about the trials which were chosen for this analysis and importantly, the statistical methodology used, Psaty et al in an accompanying editorial accepted the findings of the meta-analysis and excoriated the FDA for its non-performance as far as taking adequate safety measures regarding rosiglitazone use. The ensuing fallout created a media furore with conspiracy theories amongst others taking center stage and scientific debate taking a backseat, leading to unnecessary panic and stress to patients already on rosiglitazone therapy. Amidst all this, words of sanity reiterated the need for a more calmer and considered approach, and that whilst asking that patients be told about the possibility of these risks, one should wait for the final publication of the RECORD study as well as other long term studies which would give a more balanced view of the controversy. The recent publication of the final RECORD results showed that whilst rosiglitazone did have a two fold increase in the risk for heart failure, there was no increase in the risk for other cardiovascular morbidities or cardiovascular mortality caused by the use of this drug itself. These findings too had its critics. Whilst one would hope that this will bring an end to the rosiglitazone controversy, allowing a saner perspective on the saga, and its place in clinical therapy, this remains to be seen.