those who have had heart attacks or who have underlying heart disease -- should
talk with their doctors about whether to continue taking the drug.
The new warning comes from an analysis of publicly available, short-term
clinical studies comparing Avandia to other diabetes treatments. It finds that
Avandia increases heart attack risk by 43% -- and increases risk of death from
heart disease by 64%.
However, the overall risk was small. Among the 15,560 Avandia patients there
were 86 heart attacks and 39 deaths, compared to 72 heart attacks and 22 deaths
among the 12,283 control patients.
"In susceptible patients, [Avandia] therapy may be capable of provoking
myocardial infarction [heart attack] or death from cardiovascular causes after
relatively short-term exposure," suggest study investigators Steven Nissen,
MD, and Kathy Wolski, MPH. Nissen chairs the Cleveland Clinic's department of
cardiovascular medicine; he is past president of the American College of
The Nissen/Wolski report will be published in the The New England Journal
of Medicine. The journal today made the report public under its
Avandia is sold by itself and, as Avandamet and Avandaryl, in pills that
combined Avandia with other diabetes medications. The current findings do not
appear to immediately affect Actos (made by Takeda Pharmaceuticals), a diabetes
drug in the same class as Avandia.
Avandia Benefit, Avandia Risk
The FDA in 1999 approved Avandia on the basis of clinical trials showing
that the drug could reduce blood-sugar levels in people with type 2 diabetes.
Diabetes has been linked to both microvascular problems (problems of tiny blood
vessels) such as blindness, kidney failure, and loss of circulation in the
extremities. It has also been linked to heart disease.
But none of the trials on which Avandia was approved showed that the drug
actually prevented the greatest threats to people with diabetes: microvascular
problems, heart disease, or heart death.
In a strongly worded editorial accompanying the study, University of
Washington researcher Bruce M. Psaty, MD, PhD, says the Nissen study means
there's no good reason for most patients to take Avandia.
"There is little evidence for using this drug," Psaty tells WebMD.
"The purpose of reducing blood sugar is to prevent cardiovascular events.
Now the possibility of cardiovascular benefit associated with Avandia appears
remote -- indeed, it appears linked to harm. So the rationale for prescribing
it at this time is just not clear."
Psaty warns patients taking Avandia not to just stop using it. They should
continue taking the drug until they can discuss the matter with their
"This is not an immediate risk. It is the absence of an expected benefit
and the possibility of harm over the years," he says. "Patients should
talk with their doctors and see if they are getting the benefit they expected.
Doctors can look at the data and say whether there is a compelling reason for
them to prescribe this drug. I don't think there is."
Avandia Safe, GlaxoSmithKline Says
GlaxoSmithKline has done its own analysis of Avandia's heart safety data.
Using techniques similar to those used in the Nissen study, the GSK study
showed about a 30% increase in heart risk to patients taking Avandia.
But a study of 33,000 patients in a managed-care database showed no
increased heart risk in patients taking Avandia. Both this study and the GSK
meta-analysis were given to the FDA in August 2006.
Ongoing, long-term studies also support Avandia safety, says GSK chief
medical officer Ronald Krall, MD.
"I want to be very clear that we are confident in the benefit/risk
profile for Avandia. We believe that if it is used according to the directions
incorporated into U.S. and European labels, it is an important treatment for
patients with tpe 2 diabetes," Krall said in a news release. "We
believe that important evidence coming from long-term studies supports the
safety of Avandia."
- Are you taking Avandia?Are
you concerned about your heart? We're discussing this important
diabetes development in the WebMD Diabetes community right now.
By Daniel DeNoon
Reviewed by Louise Chang
B)2005-2006 WebMD, Inc. All rights reserved