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UK drug giant GlaxoSmithKline says interim data from a major diabetes study show no significant difference between the firm’s Avandia® (rosiglitazone) and standard therapy when it comes to cardiovascular risks, but acceptance of this view is far from universal.
GSK claimed the findings from an interim analysis of its 4,447-patient RECORD trial, published by the New England Journal of Medicine, add “further evidence to the overall cardiovascular safety profile” of Avandia. This follows the meta-analysis, also published by NEJM, which a fortnight ago suggested the drug might significantly increase the risk of heart attacks.
The study compares cardiovascular hospitalisation and death in patients treated with Avandia dual therapy (rosiglitazone plus metformin or sulfonylurea) and in patients treated with metformin and sulfonylurea in combination.
After following patients for an average of 3.75 years, the interim analysis (the study is scheduled to end in late 2008) found the risk of heart failure was 2.15 times higher among patients in the Avandia group, compared with those who did not receive the drug. Additionally, 217 patients in the Avandia group were hospitalised or died from cardiovascular events, compared with 202 taking metformin and sulfonylurea in combination.
However, GSK did state that a significant difference between the Avandia and control groups was seen only in the secondary outcome of congestive heart failure, where significantly more cases were seen in Avandia patients – “consistent with the well-known association between fluid retention and thiazolidinediones”, the class of medicine to which rosiglitazone belongs.
Dr Moncef Slaoui, chairman of R&D at GSK, said the RECORD data “add to the weight of evidence, from both previously published long-term clinical trials and other studies, that the overall ischaemic cardiovascular safety profile of Avandia is comparable to the traditional anti-diabetes treatments. Patients and physicians should find these data reassuring”.
However, in an editorial in NEJM accompanying the study Dr David Nathan, director of the diabetes centre at Massachusetts General Hospital, did not seem reassured. He claimed that the interim data “failed to provide exculpatory evidence” for the safety of Avandia, noting that while there were “too few heart attacks and other complications to definitively implicate or clear the drug, the results of this underpowered interim analysis suggest a possible adverse effect of treatment rather than the benefit that was hypothesised.”
The jury is still out on Avandia and the next episode of the saga will take place later today when a US House of Representatives committee questions FDA commissioner Andrew von Eschenbach, Dr Slaoui, and Steve Nissen, who authored the original meta-analysis linking Avandia to a 43% higher chance of having a heart attack.