Concerns about TZDs and Heart Problems
| Author: Judy Kohn, RN, BSN, CDE |
| Last Updated: Friday, September 21, 2007 |
Q: “I have been taking Avandia® for several years with no problems, but due to the recent publicity and FDA warnings about heart problems, my doctor called and wants to see me next week to discuss my medication. Can you explain better what this was all about? I am tempted to stop my Avandia right now.”
A: I can understand your concern, but I want to emphasize that you should not stop your medication without first talking to your doctor. The explanation about these recent warnings is a bit complicated, so I will attempt to provide you and other readers with the basic information, and I will encourage you to discuss this further with your doctor.
Review of Thiazolidinediones (TZDs)
Both Avandia® and Actos® are oral agents for diabetes in the category called Thiazolidinediones, (commonly referred to as TZDs for easier pronunciation). These drugs help to decrease insulin resistance by making your body more sensitive to its own insulin, and also they help to decrease the amount of glucose produced by the liver.
Recent reports of increased heart problems
The recent warnings stemmed from an article published in the New England Journal of Medicine in May, 2007, in which a meta-analysis of 42 studies showed that Avandia was associated with a significant increase (43%) in the risk of myocardial infarction (heart attack) and an increased risk of death from cardiovascular disease.
(Note: A meta-analysis is a method of summarizing previous research by reviewing and combining results from multiple clinical trials. Meta-analyses are attempted when previous studies were too small individually to achieve meaningful or statistically significant results. Because combining data from disparate groups is problematic, meta-analyses usually are considered more suggestive than definitive).
This report generated significant publicity, discussion, and controversy. The debate opened up the question of whether or not Actos has the same effect, and whether the class of TZD drugs should remain on the market. Subsequently, the FDA conducted a full advisory hearing on July 30, 2007. As a result of the FDA meeting:
- The committee voted 22-1 that despite the increased cardiovascular risk associated with Avandia, the drug should be kept available to patients with type 2 diabetes.
- The committee also voted 20-3 that Avandia increases cardiovascular risk, but agreed that the benefits of the drug outweighed the risks.
- A black box warning (the FDA's strongest form of a warning) will be required for both Avandia and Actos (see details below).
- GlaxoSmithKline (makers of Avandia) and others argued that the meta-analysis was flawed, as these types of studies reflect limitations common to all meta-analyses--meaning that the studies have different endpoints and different patient populations, and that no long-term, head-to-head clinical trial data specifically evaluates cardiovascular risk between Avandia and Actos.
After the FDA meeting, further meta-analyses and articles from the Journal of the American Medical Association reported:
- Avandia: There is an approximate doubling in risk of heart failure and a 42% increase in the risk of myocardial infarction (MI) without any effect on cardiovascular mortality.
- Actos: There is a significantly lower risk of death, MI, or stroke among patients with diabetes. It has a more favorable impact on lipids. Serious heart failure is increased, although without an associated increase in mortality.
- Firm conclusions about the risk differences between Avandia and Actos cannot be made because of the absence of head-to-head comparisons.
The following are the black boxed warnings for both drugs:
ACTOS:
Boxed Warning: Congestive Heart Failure
(please refer to the Actos website for full information)
|
AVANDIA:
Boxed Warning: Congestive Heart Failure
(please refer to the Avandia website for full information)
|
Conclusion:
As the FDA website so well stated-If you are taking Avandia:
- Do not stop taking Avandia, Avandaryl or Avandamet without first talking to your doctor about this new information.
- Discuss the best individualized treatment plan for your diabetes and other medical conditions.
- Remember that the best treatment plan is a team approach between you and your doctor.
Resources for this answer are from: The New England Journal of Medicine, May 21, 2007; Journal of the American Medical Association, Sept 12, 2007; Websites from the FDA, Actos, and Avandia.
Related Questions
Thiazolidinediones
Q:
"How do Actos® and Avandia® work?"
Long-term effects of oral agents
Q:
"I currently take Avandia® 4mg twice daily and Glucophage® 850mg twice
daily. My typical fasting is 120. My question is: What are the long-term
effects of the two drugs I am taking versus if I take the old and proven meds
like Glucotrol® or Amaryl®."
Related Links
Avandia®
http://www.avandia.com
Actos®
http://www.actos.com
FDA
http://www.fda.gov/diabetes
Important Notice: The responses provided by the team of Diabetes Educators are based on their personal experiences and expertise as practicing diabetes healthcare professionals, and are not to be considered diabetes management advice from Abbott Laboratories. Remember that information provided by the team of Diabetes Educators is for general background purposes and is not intended as a substitute for medical diagnosis or treatment by a trained professional. You should always consult your physician about any healthcare questions you may have, especially before trying a new medication, diet, fitness program, or approach to healthcare issues.
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