Results of three major studies have been presented over the past couple days at the American Diabetes Association conference.
Results of three major studies have been presented over the past couple days at the American Diabetes Association conference. While ADVANCE, ACCORD, and VADT all showed similar results, it was the VADT findings that inadvertently raised the most eyebrows.
The VADT (Veteran Affairs Diabetes Trial) is a 7.5-year trial conducted among 1792 patients and primarily aimed at studying the effects of intensive glycemic control on cardiovascular outcomes.
Chief statistician Thomas E Moritz, MS, Hines VA Hospital, surprised the audience when he declared that the controversial drug rosiglitazone (Avandia) did not seem to cause excessive negative cardiovascular events, and may potentially have a protective effect on patients.
Rosiglitazone has been controversial drug since May 2007, when the New England Journal of Medicine published a meta-analysis of42 clinical trials involving rosiglitazone by Steven Nissen, MD, Cleveland Clinic, and Kathy Wolski, MPH. The authors reported that their analysis led them to conclude that rosiglitazone “was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance.” They calculated that for patients “in the rosiglitazone group, as compared with the control group, the odds ratio for myocardial infarction was 1.43 . . . and the odds ratio for death from cardiovascular causes was 1.64.”
In response, the VA decided to drop the drug from its formulary in October 2007 and the FDA issued warnings regarding its risks.
Motivated by fear that the VADT could be putting patients at risk, Moritz’s team decided as a part of its trial to also examine whether rosiglitazone was harmful. Examining myocardial infarction, cardiovascular death, and congestive heart failure, the case-control analysis and time-dependent covariate analysis found no evidence linking rosiglitozone with cardiovascular events.
Investigator William C. Duckworth, MD, reported that over 80% of the patients across both arms were taking rosiglitazone. Of them, only about 500 patients had cardiovascular events, much less than the 650 to 700 that the investigators had anticipated.
Dr. Nissen did not find the study insights reliable, as only 80% of the patients in both groups were receiving rosiglitazone. This incomplete data, according to him, did not allow for any accurate statistical analysis regarding the safety of drug from the VADT.
In terms of the main study objectives, the researchers found that there was no significant decrease of cardiovascular deaths among patients being treated aggressively for glycemic control compared with patients receiving standard therapy. The VADT study also found that severe hypoglycemia was a major predictor of cardiovascular events. The full results of the main study findings will not be available until September.
Along with the controversies surrounding the drug, the presentation of results was surrounded by its own share of controversies. To begin with, the data from the study was compiled within just nine days after the last date of data collection in order to be ready for and presented at the ADA meeting.
It is also important to note that the information has only been provided in a presentation and abstract, and the results have yet to be published by a peer-reviewed journal. Therefore all information is still considered to be preliminary.
Additional controversy came from Avandia manufacturers GlaxoSmithKline, who before the presentation had representatives at the meeting giving reporters press releases reporting the safety findings of rosiglitazone. Some of the information in their press release was taken from an embargoed press release provided by the ADA only to reporters. GlaxoSmithKline admits that the data was provided to them by a reporter who had defied the embargo’s restrictions and sent the release to the company’s public relations firm in New York.
The long-term effects of this new Avandia information have yet to be determined, but with the tenacity that GlaxoSmithKline has shown so far, it is unlikely that this new evidence will be allowed to be ignored or forgotten.
For detailed ADA conference coverage, visit Anita Manning’s live conference blog, American Diabetes NOW