Avandia and heart attacks

Could Avandia be the next Vioxx? The NEJM with some smoke. Will fire be far behind?

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. 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.

Update -
The author of the study, Dr. Steven Nissen backs away from suggesting what to do:

Is there a case for prescribing Avandia? Are there some patients for whom the benefits outweigh the risks?
Again, I don’t think I want to go there. It’s important for me as a physician-scientist to put the data out there in a very neutral fashion, and not cast judgment about what people ought to do. We’re going to let everybody read our paper and make up their own minds.

I’ll be expecting a lot of patient calls tomorrow.

Update 2 -
MedPage Today with the best perspective thus far, comparing the findings to PremPro and Vioxx:

A meta-analysis of data from 42 clinical trials found a 43% increase in relative risk of myocardial infarction among type 2 diabetics treated with rosiglitazone (Avandia).
The odds ratio for MI was 1.43 (95% confidence interval 1.03-1.98, P=0.03), said Steven E. Nissen, M.D., of the Cleveland Clinic, lead author of the meta-analysis, which was released online today by the New England Journal of Medicine . . .
. . . To put those data in perspective, the Women’s Health Initiative (WHI), which used patient-level data, found that use of Prempro was associated with a 29% increase in relative risk in the combined endpoint of non-fatal MI and death from coronary heart disease. A 2001 study co-authored by Dr. Nissen (JAMA 2001; 286:954-959) reported that rofecoxib (Vioxx) was associated with a 2.38 OR for thromboembolic events (95% CI, 1.49-4.00 P=0.002).

Update 3 -
This smaller study touting the ulcerative colitis benefits of Avandia picked a bad day to be released.

Read more for continuing coverage on Kevin, M.D.

Comments

RJS
TZDs seem to show promise in inhibiting angiogenesis in certain tumors as well increasing the efficacy of certain types of chemotherapy in some types of cancer patients. (In a rush, otherwise I’d get you source links.)
I don’t think we’ll see either of the two major TZD players go anywhere. They’re just too interesting.
daedalus2u
The “killer ap” for Rosiglitazone is the metabolic syndrome. It is not clear if it is good for patients with underlying heart conditions.
http://care.diabetesjournals.org/cgi/content/full/27/1/256
My own opinion, is that the risk is real, and that treating the symptoms of hyperglycemia and insulin resistance is the wrong approach.
The tissue compartment where glucose and insulin concentrations matter most is in the extravascular space, far from the vessel wall, where obviously it is lower than in the blood vessel (due to consumption by intervening cells).
I appreciate that such measurements are difficult (and non-standard), but extravascular fluid is what most cells are in contact with, not bulk blood.
I suspect that hyperglycemia results from a shift in ATP production from oxidative phosphorylation to glycolysis, and it takes 19 times more glucose to supply the same ATP from glycolysis as from oxidative phosphorylation. Shifting 5% of ATP from oxidative phosphorylation to glycolysis would double glucose requirements. Glucose transport into cells is active, only through GLUT transporters. How much more glucose can the vasculature supply?
Megan
I think I would rather take insulin than a drug that’s going to cause me to have an MI, especially when diabetes already puts you at great risk for heart disease. Granted, it was just one study. I suppose as a type 1 diabetic who has never taken anything but insulin, I’m a little biased on the subject. However, as a medical professional I do feel that with insulin available, there’s really no situation in which the benefit of an oral medication with significant, well documented, side effects outweighs the benefits of said medication. Insulin has very few side effects if proper hypoglycemia education is done.
I know insulin shouldn’t be the first line treatment for type 2, but it sure seems to make more sense than MIs.
daedalus2u
In my opinion, it is unconscionable that the only endpoint the FDA used to approve it was blood glucose level.

Avandia and heart attacks

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