A prospective clinical trial of the diabetes drug Avandia has failed to clear the air regarding the blockbuster’s potential to raise cardiac risk.
GlaxoSmithKline, the drug’s maker had hoped that the so-called Record trial would quell concerns that have dogged Avandia since 2007, when a report suggested it was associated with an increased risk of heart attacks compared with other diabetes drugs.
Avandia’s annual sales fell 55% to $1.29 billion since that report surfaced.
On the surface, the Glaxo-funded trial looked promising. Newcastle University’s Philip Home and colleagues reported in last week’s Lancet that people taking Avandia did not experience increased hospitalization rates or cardiovascular mortality compared with those taking other diabetes drugs.
Home’s position on the matter, as reported by the Wall Street Journal, was that Record provided “a robust assessment of [Avandia's] cardiovascular safety.”
But in an accompanying editorial, Ravi Retnakaran and Bernard Zinman of Mount Sinai Hospital in Toronto said “definitive conclusions” about the drugs cardiovascular risk “remain elusive” because of the study’s methodological problems.
The cardiovascular event rate observed in Record was lower than expected, they said. That meant it wasn’t possible to reach firm conclusions.
The low event rate might have been caused by the coincident use of cholesterol-lowering statins in the Avandia group, or by the unexpectedly high patient drop-out rate from the study, which may have been prompted by safety concerns about Avandia that arose during the trial.
Roughly 45% of the subjects dropped out of the study before it concluded.
Amid the controversy, David Robbins, a professor of medicine at Kansas found a common denominator everyone could agree with. Avandia certainly did not improve cardiovascular outcomes, he reasoned to the Journal. “What we really want in diabetes is…drugs that are reducing cardiovascular events.”