Ask The Expert
Medications
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)
- Thiazolidinediones (TZDs), including ACTOS, cause or exacerbate congestive heart failure (CHF) in some patients. After initiation of ACTOS and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of ACTOS must be considered.[1]
- ACTOS is not recommended in patients with symptomatic heart failure.
Initiation of ACTOS in patients with established NYHA Class III or IV heart
failure is contraindicated.[1]
AVANDIA:
Boxed Warning: Congestive Heart Failure
(please refer to the Avandia website for full information)
- Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients (see WARNINGS). After initiation of AVANDIA, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of AVANDIA must be considered.
- AVANDIA is not recommended in patients with symptomatic heart failure. Initiation of AVANDIA in patients with established NYHA Class III or IV heart failure is contraindicated. (See CONTRAINDICATIONS and WARNINGS.)
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.
Sources:
- 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
Resource Links
Launches new window
|
|