There is not a higher risk of heart attack and cardiovascular events in patients who take controversial type 2 drug Avandia (rosiglitazone), researchers at the Duke Clinical Research Institute (DCRI) reported after carrying out a re-analysis of data from a pivotal study.
The DCRI researchers re-assessed the original findings of RECORD, a study that drew criticism from an 2010 FDA advisory panel. Yesterday, an FDA advisory panel recommended loosening the restrictions on Avandia.
The Duke researchers reported their re-assessment in the American Heart Journal and also presented at the FDA advisory hearing on June 5-6, 2013.
Avandia’s sales plummeted in the USA after the FDA restricted its usage in 2011, following concerns linking rosiglitazone’s usage with a higher risk of heart attacks and death from cardiovascular causes. Avandia, and all medications containing rosiglitazone were taken off the market in the European Union.
GlaxoSmithKline funded this new analysis, which had been an FDA requirement.
Lead study author, Kenneth W. Mahaffey, M.D., associate director of the DCRI, said (before the FDA panel convened):
“We were pleased to be chosen to perform this re-evaluation and we look forward to presenting our findings and being part of the FDA advisory committee discussion.”
The team also expanded the analysis. They started off by identifying the participants who had dropped out or declined to seek follow-up care – they managed to identify 328 of them, despite logistical challenges.
The DCRI team also examined the data again using typical procedures and a blinded, unbiased systematic approach to identify all potential deaths, heart attacks and strokes. The data were processed and sent to a team of doctors for judgment.
Mahaffey said “I am proud of the dedicated and professional way that the DCRI team approached this effort.”
The DRCI researchers confirmed that there was no statistically significant difference in the risk of cardiovascular events between participants on Avandia and metformin/sulfonylurea (the comparison drug). The original RECORD study had similar results.
The DCRI analysis also found no statistically significant difference between Avandia and metformin/sulfonylurea when they compared results using a contemporary set of cardiovascular endpoint definitions that the FDA is currently developing.
The researchers wrote that their findings, along with the additional sensitivity analyses they performed, support the original RECORD results “suggesting that when using essentially the same raw data, the observations were not affected by different end points and other factors”.
Mahaffey and colleagues concluded:
“These analyses using the original RECORD or new FDA endpoint definitions show similar treatment effects of rosiglitazone compared with the original RECORD results.”
Mahaffey and several other study authors have received research grants and fees from GlaxoSmithKline. Full disclosures are available at www.dcri.org
Written by Christian Nordqvist