Trials Offer Important Safety Information On Cardiovascular Effects Of AVANDIA
Two long-term, large-scale and independent studies evaluating cardiovascular (CV) outcomes in people with type 2 diabetes enrolled more than 9,300 patients taking AVANDIA (rosiglitazone maleate) and provide more than 20,000 patient years of additional experience with AVANDIA. The Veterans Affairs Diabetes Trial (VADT), through two separate analyses, concluded that based on results from VADT, there is no evidence to suggest that use of AVANDIA increases the risk for CV mortality and morbidity in patients with type 2 diabetes. A second trial, The Action to Control Cardiovascular Risk in Diabetes (ACCORD), found that AVANDIA was not associated with any increased risk of death. These findings display a safety profile consistent with results from other long-term studies with AVANDIA. These studies were presented during the 68th Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, CA.
"The findings on AVANDIA should be reassuring to physicians who prescribe AVANDIA and patients who use AVANDIA for their type 2 diabetes," added R. Paul Aftring, MD, PhD, AVANDIA Clinical Lead at GlaxoSmithKline. "The safety findings on AVANDIA from these two trials add substantial patient experience to the large body of existing evidence on the safety profile of the medication."
Findings from VADT
VADT evaluated whether intense blood sugar control in patients with type 2 diabetes would reduce major CV events. The study continued for 7.5 years. In total, 1,704 patients enrolled in VADT took AVANDIA.
The primary result of VADT did not show that intensive blood sugar control (HbA1c levels below 7%) had a statistically significant effect on reducing major CV events associated with diabetes. However, there was a favorable trend in reducing all CV events, except CV death and inoperable heart disease, among the patients in the intensive arm. There were significantly fewer CV events in the trial than predicted.
In the trial, investigators said that they were "more aggressive" with AVANDIA and other medications in the intensive arm to achieve and maintain tight glycemic targets. The investigators found that in VADT, there were no increased deaths associated with any of the medications used in the trial, including AVANDIA.
Findings from ACCORD
ACCORD, which investigated whether or not intensive blood control would reduce CV events in patients with type 2 diabetes who had either established cardiovascular disease or additional CV risk factors, was presented at a press conference during the ADA Scientific Sessions and published simultaneously in the New England Journal of Medicine. The study had a mean follow-up of 3.5 years. In total, 7,623 patients enrolled in the ACCORD trial took AVANDIA, representing more than 19,200 patient years of experience with the medication.
The investigators found that, as compared with standard therapy, the use of intensive therapy to reach the study's A1C goal for 3.5 years did not significantly reduce major CV events. Although they found an increase in CV deaths among these high-risk patients who were in the intensive arm, the death rates from ACCORD were substantially lower than investigators predicted at the outset of the trial.
In their analysis, the investigators noted that "preliminary nonprespecified exploratory analyses of episodes of severe hypoglycemia after randomization and differences in the use of drugs (including rosiglitazone), weight change, and other factors did not identify an explanation for the mortality finding."
Additionally, an accompanying editorial in the New England Journal of Medicine states, " ... the ACCORD trial investigators concluded that patients in the standard-control group and those in the intensive-control group had similar risks and rates of death, whether or not they were prescribed rosiglitazone."