Avandia No Riskier Than Other Diabetes Drugs Says Interim Study

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Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry;  Cardiovascular / Cardiology
Article Date: 06 Jun 2007 - 5:00 PST

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Interim results of a drug trial showed that Avandia (chemical name rosiglitazone maleate), made by GlaxoSmithKline (GSK), was linked to slightly higher risk of heart problems compared to other drugs used to treat diabetes type 2 but the difference was so small it could be down to chance; it was not statistically significant researchers said.

The study reveals the interim results of RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes) a prospective clinical trial, and is published online in the New England Journal of Medicine (NEJM).

There has been controversy recently over whether Avantia, which earned GSK 1.4 billion US dollars in sales last year, raises the risk of heart attack and death from cardiovascular problems in patients with type 2 diabetes. This followed last month's publication (also in NEJM) by US cardiologist Steve Nissen of a meta-analysis review of Avandia covering several studies and suggested that taken as a whole they pointed to a raised risk of heart attack by 43 per cent.

This latest study reporting on the interim analysis of RECORD is the work of Philip D Home and colleagues who form the steering committee of RECORD.

RECORD is a prospective clinical trial that investigates the cardiovascular outcomes in 4,447 patients with type 2 diabetes being treated at several clinics. It compares hospital admissions and deaths in 2,220 patients who received Avandia dual therapy (Avandia with metformin or sulfonylurea) to that of 2,227 patients treated with metformin and sulfonylurea in combination.

The researchers say that because the mean follow-up in this interim analysis is only 3.75 years, this limited the statistical power to detect differences in the treatment received by the Avandia and the non-Avandia groups.

They found no statistically significant differences between the Avandia and the control groups with respect to heart attack and death from cardiovascular causes, or any cause, they said, but there were more patients with heart failure in the Avandia group compared with the control group.

Home and colleagues concluded that:

"Our interim findings from this ongoing study were inconclusive regarding the effect of rosiglitazone (Avandia) on the overall risk of hospitalization or death from cardiovascular causes."

"There was no evidence of any increase in death from either cardiovascular causes or all causes. Rosiglitazone was associated with an increased risk of heart failure. The data were insufficient to determine whether the drug was associated with an increase in the risk of myocardial infarction," they added.

In a prepared statement, GSK said the link with congestive heart failure was already known, and is consistent with the fluid retention effect seen in patients taking TZDs, the class of drugs that includes Avandia. Fluid retention can get worse and it can result in heart failure, said GSK, but what was important about this interim analysis was the fact that despite the increase in congestive heart failure, there was no evidence that the Avandia group had more hospitalizations and deaths due to cardiovascular events.

Last month, the US Food and Drug Administration issued a safety alert on Avandia, pointing to the possibility of elevated risk of heart attack and heart related deaths in patients with diabetes type 2, but that the evidence was contradictory. The FDA approved Avandia as a type 2 diabetes treatment in 1999. About 20 million Americans are affected by the disease.

Their advice was that patients taking Avandia, especially if they have underlying heart disease or have elevated risk of heart attack should evaluate their options with their doctors in the light of this inconclusive information.

Also last month, Diabetes UK said the NEJM Nissen study was not a cause for alarm, pointing out that its limitations meant the results could not be considered conclusive and that more research was needed. In the meantime they endorsed the UK's Medicines and Healthcare products Regulatory Authority (MHRA) statement that rosiglitazone was a safe and effective treatment for those diagnosed with Type 2 diabetes as part of a regime that includes a well balanced diet and daily exercise.

Following this latest publication of the RECORD study's interim results, GSK has taken out several full page advertisements in US newspapers today ahead of a US congressional hearing on the FDA's evaluation of Avandia's safety record.

"Rosiglitazone Evaluated for Cardiovascular Outcomes: An Interim Analysis."
Home, Philip D., Pocock, Stuart J., Beck-Nielsen, Henning, Gomis, Ramon, Hanefeld, Markolf, Jones, Nigel P., Komajda, Michel, McMurray, John J.V., the RECORD Study Group.
N Engl J Med 2007 0: NEJMoa073394
Published online June 5, 2007.

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Written by: Catharine Paddock
Writer: Medical News Today


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