FDA continues to closely monitor the cardiovascular safety of rosiglitazone

On February 22, 2010, FDA released a safety alert reminding healthcare professionals of the agency’s ongoing concerns regarding the cardiovascular safety of rosiglitazone (Avandia, GlaxoSmithKline). However, this is not the first warning the agency has posted regarding rosiglitazone and its cardiovascular safety. FDA previously released a communication to the public regarding the possible association between rosiglitazone and increased cardiovascular risk in a 2007 safety alert.

At the center of this most recent communication is new data from the large, randomized Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, which was specifically designed to evaluate the cardiovascular safety of rosiglitazone in type 2 diabetes. In addition, a number of observational studies evaluating the cardiovascular safety of rosiglitazone have been published and are being reviewed by the agency.

The RECORD trial randomized 2,220 patients with type 2 diabetes to receive rosiglitazone plus other diabetes medications (metformin or a sulfonylurea) and 2,227 patients to receive metformin and a sulfonylurea. Patients in the study were followed for a mean of 5.5 years and were monitored for the occurrence of the composite end point of cardiovascular death and cardiovascular hospitalizations (the primary study end point). The trial reported no difference in the primary end point when comparing the rosiglitazone group [HR=0.99; 95% CI, 0.85–1.16)] to the combined metformin and sulfonylurea group. The RECORD trial results were published in the June 20, 2009 edition of the Lancet.

It is stressed in this most recent safety announcement that, “This work is ongoing and no new conclusions or recommendations about the use of rosiglitazone in the treatment of type 2 diabetes have been made at this time.”

Concerns regarding rosiglitazone’s cardiovascular safety have already significantly impacted the way the agent is used in diabetes treatment. The most recent American Diabetes Association guidelines for the treatment of type 2 diabetes mellitus recommends pioglitazone as an adjunct to metformin, but not rosiglitazone, as a treatment for type 2 diabetes mellitus when the risk of hypoglycemia is especially undesirable.

FDA plans on presenting “the totality of new and existing cardiovascular safety data on rosiglitazone” at a joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees in July 2010. According to agency officials, “At that meeting, the Advisory Committee will provide an updated assessment of the risks and benefits of rosiglitazone in the treatment of type 2 diabetes.” Until then, FDA is recommending healthcare professionals follow the recommendations in the drug label when prescribing rosiglitazone.

For more information, go to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm201446.htm.