Circ: Despite ongoing drama, Avandia, Actos have similar CV risks

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After much debate on whether or not diabetes drug rosiglitazone (Avandia, GlaxoSmithKline) should be pulled from the shelves due to its potential to cause increased cardiovascular risk in patients, results of a recent study have shown that the risk of MI, heart failure (HF) or death in patients administered either rosiglitazone or pioglitazone (Actos, Takeda) were similar--almost 4 percent.

"Currently, there are 2 thiazolidinediones (TZDs), rosiglitazone and pioglitazone, approved in the U.S. for treatment of type 2 diabetes mellitus," the authors wrote. However, neither drug has been studied in an individual randomized, double-blind, clinical trial sufficiently populated or designed to definitively evaluate the effect of treatment on CV morbidity and mortality."

To bulk up these data, a study published in this month’s Circulation: Cardiovascular Quality and Outcomes, evaluated 36,628 patients who were taking either of the two drugs between Jan. 1, 2001, and Dec. 12, 2005, to compare the risk of MI, heart failure and death rates of each therapy. The researchers excluded 3,475 patients.

Debra Wertz, PharmD, of HealthCore, a subsidiary of WellPoint, a health insurance company in Wilmington, Del., and colleagues divided patients into two groups—those administered rosiglitazone (14,469) and pioglitazone (14,469)—and adjusted data for multivariate factors including age, gender and previous incidences of blood vessel diseases and diabetes-related complications.

The average age was 54 and males comprised 58 percent. Death records were obtained from the National Death Index, maintained by the National Center for Health Statistics. Wertz et al performed a mean treatment follow-up of 14 months and 19 months post-treatment follow-up.

Within each arm of the study, less than 1 percent of patients had a pre-index MI or HF diagnosis and 2.2 percent of patients had a pre-index ischemic heart disease diagnosis.

The researchers recorded that 4.15 percent of patients taking rosiglitazone and 4.14 percent of patients administered pioglitazone experienced heart attack, HF, both, or death within a 33-month follow-up period. Crude event rates were reported to be much greater in this patient population and were 86.21 per 1,000 person-years for rosiglitazone and 86.10 per 1,000 person-years for the same aged patients on pioglitazone.

Wertz and colleagues, after studying event rates in a subdivision of patients aged 65 years and older, found that 355 of the 2,558 rosiglitazone patients had an event compared with 393 of the 2,819 patients administered pioglitazone.

"The event rate for rosiglitazone was 26.38 per 1,000 person-years and 25.76 per 1,000 person-years for pioglitazone," the authors wrote.

Broken down, 96 patients on rosiglitazone and 121 patients on pioglitazone experienced heart attack and 265 taking rosiglitazone and 243 taking pioglitazone experienced HF.

Additionally, 24 patients on rosiglitazone and 18 on pioglitazone experienced both MI and HF and death occurred in 217 patients administered rosiglitazone and 217 patients administered pioglitazone.

Overall, researchers reported that the rates of adverse events were similar for both study arms—around 4 percent.

"Besides its findings that rosiglitazone and pioglitazone have comparable risks, what distinguishes this latest study from other claims-based analyses is its analysis of death records, which include out-of-hospital deaths," Wertz said. According to Wertz, the current study has a longer follow-up period compared to prior studies of the drug.

Previous studies have shown different results than the current study, influencing FDA to take a closer look at the possible risk involved for patients administered the drug rosiglitazone after compounding evidence has shown a possible higher risk for CV events compared to other TZDs like pioglitazone, used to treat diabetes.

"There are several possible explanations for the absence of an elevated risk for rosiglitazone in the present analysis," the authors wrote. "As discussed, one is the possibility that the commercially insured, relatively young population studied was less susceptible to an increased risk, and/or that there were too few events to document such risk, especially among the elderly."

Currently, the FDA is continuing to weigh its decisions on rosiglitazone after members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee met and voted on the proper actions that should be taken for the drug during a July 14-15 meeting.

"Further research to refine methodology, identify population segments potentially at elevated risk, and validate events/exposure using additional data elements such as medical charts and/or surveys is essential," the authors concluded. "Nevertheless, this study provides valuable results that contrast previously published observational data and adds to the body of evidence available for risk-benefit profile assessment of TZDs in the treatment of diabetes."