Claims that meta-analysis findings cast doubt on the cardiovascular safety of the glucose-lowering drug rosiglitazone and the drug approval system have been refuted in a letter published by the Lancet.
Dr Ronald Krall, chief medical officer at GlaxoSmithKline (GSK), the drug’s manufacturer, argues that three large, prospective trials support the drug’s cardiovascular safety profile.
In particular, he highlights that the independent data safety monitoring board for the ongoing Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes (RECORD) trial recently said that the trial should continue after reviewing an interim analysis of nonblinded cardiovascular endpoints.
Dr Krall asserts that the findings of both ADOPT (A Diabetes Outcome Progression Trial) and DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication), which showed that rates of cardiovascular endpoints were similar between rosiglitazone and other treatments or placebo, are more reliable than the results of meta-analyses.
He notes that in addition to RECORD, there are other cardiovascular outcomes trials under way that will provide information on the cardiovascular safety profile of rositglitazone, notably the Bypass Angioplasty Revascularization Investigation Type 2 Diabetes (BARI 2D) trial and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
The letter comes in response to the publication of a meta-analysis in the New England Journal of Medicine and related articles, suggesting rosiglitazone is associated with an increased risk of myocardial infarction and cardiovascular death.
Dr Krall concludes: “We believe that these studies provide clear evidence of the cardiovascular safety of rosiglitazone and that the estimates of cardiovascular morbidity meta-analyses completed to date are not robust.
“The drug use and approval system is working. We should stay the course and allow ongoing trials to provide their definitive answers.”
Lancet 2007; advance online publication