Diabetes News - Avandia Study
5/21/2007
May 21, 2007
Today the New England Journal of Medicine released a study to be
published in the June 14 edition, in which analysis of 42 studies of the
diabetes medicine Avandia (rosiglitazone) suggested therapy with this
medicine was associated with an increased risk of heart attack and
potentially an increased risk of death from cardiovascular causes.
Bottom Line:
The doctors at Boulder
Endocrinology have reviewed the study and would make the following
observations:
1. The study raises potential concerns about the safety of rosiglitazone
(Avandia), but is a preliminary analysis that will require additional
study to confirm these findings.
2. The overall risk for each person taking rosiglitazone was small (for
example, in the "small trials" included in the analysis, rate of heart
attack were 0.43% in those taking rosiglitazone and 0.36% in those
taking another diabetes drug or placebo).
3. People should not stop rosiglitazone (Avandia) prior to reviewing the
potential risks and benefits with their doctor.
4. We recommend our patients continue rosiglitazone (Avandia) until
their next appointment, at which time the following options can be
considered:
- continue taking rosiglitazone
- switch to pioglitazone (Actos, a related medicine of
the TZD class)
- switch to a diabetes medication from a different
class
- stop rosiglitazone without starting new medication
Details:
The authors of the study,
who work at the Cleveland Clinic (a well-known academic medical center)
analyzed data that is publicly available from several sources, including
the website for GlaxoSmithKline, the company that makes Avandia, and
from the FDA. They originally looked at data from 116 trials, and
ultimately found 42 that met their criteria and were included in the
final analysis. These studies were at least 24 weeks in duration, were
randomized (patients were randomly assigned to receive rosiglitazone vs.
either another diabetes drug or placebo), and reported data for
cardiovascular outcomes.
This analysis found that the odds ratio for having a myocardial
infarction (heart attack) was 1.45 and for cardiovascular death was
1.64. The "odds ratio" is a statistical term comparing events. This
could be rephrased "patients who had a heart attack were 1.45 times more
likely to have taken rosiglitazone than another medication or placebo"
and "patients who had died of cardiovascular causes were 1.64 times more
likely to have taken rosiglitazone than another medication or placebo."
For these comparisons, the risk of
heart attack was statistically significant, meaning similar results
could be expected by chance <5% of the time, and the results for
cardiovascular death were not statistically significant, with p value
0.06, meaning similar results could be expected by chance 6% of the
time. The authors comment
that the results are of the type called meta-analysis, which means they
are using data from multiple studies that included different groups of
patients, were of different duration, and had variable outcomes. These
variations in the studies make it possible that the conclusions are
somehow biased. Small changes in the rates of cardiovascular disease in
the studies might have lead to different conclusions.
The authors state that the reason for
the apparent increase risk of bad outcomes is unknown, and it is not
known if similar concerns would be seen with other medications in this
class (currently Actos, pioglitazone, is the only other approved "TZD").
The authors requested that GlaxoSmithKline release more detailed data
from the studies to an independent source so that more detailed analysis
could be performed. The
authors conclusion from the study was "despite
these limitations, our data point to the urgent need for comprehensive
evaluations to clarify the cardiovascular risks of rosiglitazone. The
manufacturer's public disclosure of summary results for rosiglitazone
clinical trials is not sufficient to enable a robust assessment of
cardiovascular risks. The manufacturer has all the source data for
completed clinical trials and should make these data available to an
external academic coordinating center for systematic analysis. The FDA
also has access to study reports and other clinical-trial data not
within the public domain. Further analyses of data available to the FDA
and the manufacturer would enable a more robust assessment of the risks
of this drug. Our data suggest a cardiovascular risk associated with
the use of rosiglitazone. Until better precision of the estimates of the
risks of this treatment on cardiovascular events can be delineated in
patients with diabetes, patients and providers should give careful
consideration to the risks and benefits of their overall treatment plans."
(emphasis added) More
Information:
Statement from the American
Heart Association, American Diabetes Association, and American College
of Cardiology regarding the study.
Abstract from the New
England Journal study.
Response from GlaxoSmithKline
(maker of Avandia).
Editorial in Lancet (medical
journal) calling for balanced response.
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