To TZD or not to TZD?
The ongoing Avandia and Actos safety debate
Yes, unless you have congestive heart failure. Read on.
When the New England Journal of Medicine (NEJM) talks, people listen; then they panic.
It is understandable with an article entitled, "Effect of Rosiglitazone [Avandia] on the Risk of Myocardial Infarction and Death from Cardiovascular Causes" which was published in Spring 2007, and the fact that millions of people use Avandia since its release in 1999. (Thiazolidindiones, or TZDs, is the drug classification that includes Avandia and Actos.)
This meta-analysis collected data from 42 trials whose subjects were studied at least 24 weeks, had a randomized control group not receiving Avandia, and had data on heart attack rates and death from cardiovascular causes (like congestive heart failure). Participants were predominantly men, had a mean A1C level of 8.2%, and the age of the subjects was approximately 56 years.
The media took one finding out of context from this comprehensive, exacting review and went wild. Do you recall reading or hearing in the news that people who take Avandia have a 43% increased risk of heart attack and a 64% increased risk of dying from cardiovascular disease? The devil is in the details!
The authors of the study carefully compared two large studies, the Diabetes REducation Assessment with Ramipril and Rosiglitazone Medication (DREAM) and A Diabetes Outcome Prevention Trial (ADOPT), among others, and tested them by statistical heterogeneity (very official, indeed). In terms of shear numbers, 86 of 15,560 people on Avandia reported at least one heart attack and there were 39 cardiovascular-related deaths identified. For the control group of 12,283 (note the 3,000 fewer people) NOT on Avandia, 72 had heart attacks and 22 had cardiovascular related deaths. The data was collected based on reports without standard methods to validate the outcome, meaning a few events falsely classified could have dramatically changed these findings.
Had the media focused on the authors' statement, "results are based on a relatively small number of events, resulting in odds ratios that could be affected by small changes in the classification of events," it would have done the world a favor. That's not to discount the importance of communicating potential risks so they can be minimized. These studies did not look at previous heart conditions or prescribing practices (if the TZDs were given to high-risk individuals the data would be skewed).
The potential harm this caused is alarming. As a practicing diabetes educator, I've observed the same people who cannot identify a carbohydrate choice voice the notion that Avandia or Actos cause heart attacks. Several have stopped their medication without their healthcare provider's knowledge. Keep in mind the study participants already had soaring A1C levels that put them at risk for heart consequences.
Next, the Food and Drug Administration (FDA) held a hearing and voted 22 to 1 that Avandia should continue to be marketed in the U.S., and recommended warnings be placed in the prescribing information regarding subpopulations at increased risk for heart events (people with heart conditions or those who have Avandia added to their insulin program).
The researcher of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes trial (RECORD) found results showing no statistical significant increase in heart attacks, as published in NEJM. And the Endocrine Society and American Diabetes Association issued statements ("meta-analysis was not definitive" and "visit your doctor," respectively). In the midst of all of this, the PROactive Study (PROspective PioglitAzone Clinical Trial In MacroCascular Events) released safety information about Actos. Gotta love it!
There is no recall. You'll find plenty of lawyers ready to defend you on the Web. When in doubt, talk it out. Please involve your healthcare providers about any medication issues before you take action. Report any swelling of the ankles or shortness of breath. Think of all of the people who threw out their Avandia or Actos whose glucose levels are rising, putting themselves at risk for cardiovascular/life-altering events.
To TZD, or not to TZD? Ponder the cleverly named research studies: is this a DREAM, time to ADOPT or be PROactive, and for the RECORD: PERHAPS (Please Explain Research Helpfully And Preferably Simplistically). Question what is best for you with your healthcare provider.
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NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.
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