The New England Journal of Medicine has published an interim analysis of the RECORD Study following publication 2 weeks ago of a meta-analysis that raised concerns about the cardiovascular safety of rosiglitazone (Avandia®).
The RECORD study (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes) is a randomised controlled trial expected to last for 6 years comparing the intervention of metformin and sulphonylurea with metformin and rosiglitazone with a primary outcome of hospital admission or death from cardiovascular causes.
This interim analysis has been conducted on data with a mean follow-up of 3.75 years. The only endpoint reaching statistical significance in this analysis is for congestive heart failure; this is already known to be more likely in patients taking rosiglitazone. [Hazard ratio 2.24; 95% confidence interval 1.27 - 3.97, p=0.006].
There is a trend towards more myocardial infarctions [Hazard ratio 1.16; 95% confidence interval 0.75 - 1.81, p=0.50] in the rosiglitazone arm although this was not statistically significant. The addition of events that are pending adjudication does move this trend towards greater significance [Hazard ratio 1.23; 95% confidence interval 0.81 - 1.86, p=0.34] although still not statistically significant.
It should be noted that the RECORD study is a non-inferiority study aiming to demonstrate that there is no difference between the two treatment alternatives in terms of the primary outcome. This interim analysis fails to demonstrate non-inferiority as explained in an editorial. This fact, combined with the trends towards more myocardial infarctions observed in the data, leads this editorial to conclude that, "there is continued uncertainty about the cardiovascular safety of rosiglitazone".
There are two further editorials, one by a diabetologist and one jointly authored by a cardiovascular epidemiologist and a drug-safety expert. Both editorials recommend assessment of risk and benefit and that more research needs to be done to fully understand the cardiovascular safety profile of rosiglitazone. The latter editorial also points out that rosiglitazone is associated with weight gain, adverse effects on low-density lipoprotein cholesterol, an increased risk of heart failure and an increased risk of fractures in women.
Action: This interim analysis fails to provide any reassurance with respect to the cardiovascular safety of rosiglitazone. MHRA advice recommends that patients currently taking rosiglitazone discuss the risks and benefits of continued treatment at their next routine appointment.