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Avandia News
Finding of Increased Heart Attack, Death in Diabetes Patients
from Avandia(rosiglitazone) Sparks FDA Alert
FDA issues immediate alert on the drug marketed as Avandia.
May 21, 2007 – Rosiglitazone, a drug widely used to
treat type 2 diabetes, was found to significantly increase
the risk of heart attacks and death from cardiovascular causes
in a study of a wide range of data and clinical trials. The
Food and Drug Administration immediately issued an alert on
the drug marketed as Avandia. The study's authors also question
the approval process used by the FDA for the approval of drugs
to treat diabetes.
The New England Journal of Medicine published the study online
today, ahead of its print publication on June 14, along with
an editorial calling for changes in the current bill being
shaped in Congress to make changes in the practices of the
FDA.
"Rosiglitazone was associated with a significant increase
in the risk of myocardial infarction and with an increase
in the risk of death from cardiovascular causes that had borderline
significance," write the study authors, Steven E. Nissen,
M.D., Department of Cardiovascular Medicine, Cleveland Clinic,
and Kathy Wolski, M.P.H.
The authors do note, "Our study was limited by a lack
of access to original source data, which would have enabled
time-to-event analysis.
"Despite these limitations, patients and providers should
consider the potential for serious adverse cardiovascular
effects of treatment with rosiglitazone for type 2 diabetes."
The study included searches of the published literature,
the Website of the FDA and clinical-trials registry maintained
by the drug manufacturer (GlaxoSmithKline). Of 116 potentially
relevant studies, 42 trials met the inclusion criteria. Mean
age of subjects in the 42 trials was 56.
There were 86 myocardial infarctions in the rosiglitazone
group and 72 in the control group. There were 39 deaths from
cardiovascular cause in the rosiglitazone group and 22 in
the control group.
In the rosiglitazone group, as compared to control group,
the odds ratio for myocardial infarction was 1.43 (43%) and
the odds ratio for deaths from cardiovascular causes was 1.64
(65%).
"These emerging findings raise an important question
about the appropriateness of the current regulatory pathways
for the development of drugs to treat diabetes," the
authors write.
"The FDA considers demonstration of a sustained reduction
in blood glucose levels with an acceptable safety profile
adequate for approval of antidiabetic agents. However, the
ultimate value of antidiabetic therapy is the reduction of
the complications of diabetes, not improvement in the laboratory
measure of glycemic control."
The editorial, Rosiglitazone and Cardiovascular Risk, is
by Bruce M. Psaty, M.D., Ph.D., and Curt D. Furberg, M.D.,
Ph.D.
They focus on the Food and Drug Administration Revitalization
Act, which was passed by the Senate on May 10 and is now in
the House.
"It has many strengths," the say but none of its
provisions would necessarily have identified the cardiovascular
risks of rosiglitazone "in a timely fashion."
They suggest "a true life-cycle approach, as advocated
by the Institute of Medicine, would continue the evaluation
of both efficacy and safety after approval convert surrogate
end points into clinically meaningful outcomes, integrate
new information about health benefits and risks, and communicate
those findings effectively to patients and physicians.
The conclude by saying "The health of the public would
benefit from additional revisions to the drug-safety legislation
as in moves through the House of Representatives."
Source: Effect of Rosiglitazone on the Risk of Myocardial
Infarction and Death from Cardiovascular Causes by Steven
E. Nissen, M.D., and Kathy Wolski, M.P.H., New England Journal
of Medicine.
>> New England Journal of Medicine Online
FDA Issues Safety Alert on Avandia
The U.S. Food and Drug Administration (FDA) is aware of a
potential safety issue related to Avandia (rosiglitazone),
a drug approved to treat type 2 diabetes. Safety data from
controlled clinical trials have shown that there is a potentially
significant increase in the risk of heart attack and heart-related
deaths in patients taking Avandia.
However, other published and unpublished data from long-term
clinical trials of Avandia, including an interim analysis
of data from the RECORD trial (a large, ongoing, randomized
open label trial) and unpublished reanalyses of data from
DREAM (a previously conducted placebo-controlled, randomized
trial) provide contradictory evidence about the risks in patients
treated with Avandia.
Patients who are taking Avandia, especially those who are
known to have underlying heart disease or who are at high
risk of heart attack should talk to their doctor about this
new information as they evaluate the available treatment options
for their type 2 diabetes.
FDA's analyses of all available data are ongoing. FDA has
not confirmed the clinical significance of the reported increased
risk in the context of other studies. Pending questions include
whether the other approved treatment from the same class of
drugs, pioglitazone, has less, the same or greater risks.
Furthermore, there is inherent risk associated with switching
patients with diabetes from one treatment to another even
in the absence of specific risks associated with particular
treatments. For these reasons, FDA is not asking GlaxoSmithKline,
the drug's sponsor, to take any specific action at this time.
FDA is providing this emerging information to prescribers
so that they, and their patients, can make individualized
treatment decisions.
"FDA remains committed to assuring that doctors and
patients have the latest information available to make treatment
and medication use decisions. In this case, FDA is carefully
weighing several complex sources of data, some of which show
conflicting results, related to the risk of heart attack and
heart-related deaths in patients treated with Avandia,"
said Steven Galson, M.D., M.P.H., director of FDA's Center
for Drug Evaluation and Research. "We will complete our
analyses and make the results available as soon as possible.
FDA will take the issue of cardiovascular risk associated
with Avandia and other drugs in this class to an Advisory
Committee as soon as one can be convened."
Avandia was approved in 1999 for treatment of type 2 diabetes,
a serious and life threatening disease that affects about
18 to 20 million Americans. Diabetes is a leading cause of
coronary heart disease, blindness, kidney failure and limb
amputation. Since the drug was approved, FDA has been monitoring
several heart-related adverse events (e.g., fluid retention,
edema and congestive heart failure) based on signals seen
in previous controlled clinical trials of Avandia alone and
in combination with other drugs, and from postmarketing reports.
FDA has updated the product's labeling on several occasions
to reflect these new data, most recently in 2006. The most
recent labeling change for Avandia also included a new warning
about a potential increase in heart attacks and heart-related
chest pain in some individuals using Avandia. This new warning
was based on the result of a controlled clinical trial in
patients with existing congestive heart failure.
Recently, the manufacturer of Avandia provided FDA with a
pooled analysis (meta analysis) of 42 randomized, controlled
clinical trials in which Avandia was compared to either placebo
or other anti-diabetic therapies in patients with type 2 diabetes.
The pooled analysis suggested that patients receiving short-term
(most studies were 6-months duration) treatment with Avandia
may have a 30-40 percent greater risk of heart attack and
other heart-related adverse events than patients treated with
placebo or other anti-diabetic therapy. These data, if confirmed,
would be of significant concern since patients with diabetes
are already at an increased risk of heart disease.
March 27, 2007
Better Diabetes Care May Lead to Reduced Blindness, Kidney
and Heart DiseaseOne of the first studies of quality improvement
in diabetes care
May 18, 2007
Diabetes Drug Spending May Surge 70% by 2010, Cancer Now Drives
Specialty DrugsMedco finds generics, Medicare Part D keeping
increases down
May 17, 2007
Women with Heart Disease and Diabetes Get Less Care Than Men
Women on Medicare fare better than those on private insurance
May 14, 2007
Senior Citizens Who Experience Depression More Likely to Get
Diabetes 2 million older adults experience depression, 15.3%
of over 65 have diabetes
Increasing Rate of Diabetes Linked to Increased Cardiovascular
Disease
Call for aggressive efforts to prevent diabetes, control
CVD risks
March 28, 2007
Diabetes, High Blood Pressure Trump Race in Causing Heart
Failure Among Older Americans African-Americans have more
heart failure because they have more diabetes, hypertension
Major Heart, Diabetes Groups Urge Caution in Wake of Avandia
Warning
Study raises concerns; Groups advise patients with diabetes
to talk to their doctor
May 22, 2007 – The risk of heart attack and death for
type 2 diabetes patients taking the drug Avandia “appears
to be small”, but “must be considered carefully,”
says a statement issued Monday by the American College of
Cardiology, American Diabetes Association and American Heart
Association. They advise patients using this drug should talk
to their health care provider to determine the most appropriate
course of action.
Avandia Drug Maker Disagrees with Study Saying the Diabetes
Drug Increases Heart Attacks, Deaths
GlaxoSmithKline says it's “highly effective”
treatment for type 2 diabetes
May 22, 2007 – The maker of the diabetes drug Avandia,
GlaxoSmithKline, responded quickly to an online study published
Tuesday by the New England Journal of Medicine indicating
the drug, highly popular for treating type 2 diabetes, significantly
increased the risk of heart attack and death.
Senate Committee Wants Answers About Avandia, Company
Defends Record
Committee leaders send letters to FDA and GlaxoSmithKline
May 22, 2007 – The Senate Finance Committee leadership
obviously had their guns loaded when the New England Journal
of Medicine published a study yesterday showing the type 2
diabetes drug Avandia (rosiglitazone) significantly increases
the risk of heart attack and death. And, the drug-maker quickly
responded to the senators.
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