Help-Avandia and Heart problems

[rwguinn]

I am getting confused right now over this Avandia mess. I am taking Avandia with Metformin, since Metformin alone did not keep blood sugar under control, even with diet and exercise (which I admit I am not as meticulous about as I should be, but I have also had surgery on both knees and it only helped a little bit!)
Some of the things i have read make it seem that heart attach is imminent, while others mention in passing that the situation is applicable to those taking Avandia and insulin. I am seeing thedocthisweek,but I want to be as informed as possible.
Is there Anybody who can clarify this, even a little bit?

 

[fls]

I am getting confused right now over this Avandia mess. I am taking Avandia with Metformin, since Metformin alone did not keep blood sugar under control, even with diet and exercise (which I admit I am not as meticulous about as I should be, but I have also had surgery on both knees and it only helped a little bit!)
Some of the things i have read make it seem that heart attach is imminent, while others mention in passing that the situation is applicable to those taking Avandia and insulin. I am seeing thedocthisweek,but I want to be as informed as possible.
Is there Anybody who can clarify this, even a little bit?

The full text of the article seems to be available online if you want to read it. It was a metanalysis, combining the results from 42 studies of any reported heart attacks and any reported deaths from cardiovascular causes. The original studies were mostly not designed to look for heart attack as an end-point, but rather glucose-lowering. And as you can see from this table, in most studies the event rate was so low that individual comparison would be impossible. In fact, six additional studies were excluded because no events were reported which would have made the analysis technically difficult. It is only by combining all the studies that the difference becomes statistically significant.

The rates are low - less than one percent - so most of the differences represent an increase of about 0.2 (range 0.07 to 0.41) percent which translates to "for every 500 (range 243 to 1429) people treated, it may cause 1 additional heart attack or death due to cardiovascular causes" if the effect is real. Of interest, the overall death rate was not significantly different. I did not see anything that suggested it was isolated to the Avandia plus insulin combination.

So are we sure that this is a real effect? No. We would be more certain if we had the results of a large trial designed to look specifically at this issue. And the one large trial in the metanalysis that was designed to look at cardiac outcomes did not demonstrate a difference. Proposed mechanisms are a demonstrated increase in LDL cholesterol on Avandia, and a demonstrated aggravation of congestive heart failure.

What does it mean for the individual? If you were able to acheive glucose control with Avandia that you were unable to acheive with other drugs, if your LDL cholesterol is not elevated and your heart function is normal, I don't think I'd trade the known benefit of glucose control for a questionable risk of heart attack (i.e. I'd stay on the Avandia). However, if you hadn't tried the other drugs that can be used in combination with Metformin, it would be reasonable to see if you can get the same benefit (glucose control) without the potential risk. Alternatively, there is apparently a study in progress that is designed to look at this issue called RECORD. I imagine that information from that study will be coming out shortly, or interim information may be made available because of the NEJM metanalysis. It would also be reasonable not to change anything until that new information is available.

Don't panic.

Linda

 

[rwguinn]

The full text of the article seems to be available online if you want to read it. It was a metanalysis, combining the results from 42 studies of any reported heart attacks and any reported deaths from cardiovascular causes. The original studies were mostly not designed to look for heart attack as an end-point, but rather glucose-lowering. And as you can see from this table, in most studies the event rate was so low that individual comparison would be impossible. In fact, six additional studies were excluded because no events were reported which would have made the analysis technically difficult. It is only by combining all the studies that the difference becomes statistically significant.

The rates are low - less than one percent - so most of the differences represent an increase of about 0.2 (range 0.07 to 0.41) percent which translates to "for every 500 (range 243 to 1429) people treated, it may cause 1 additional heart attack or death due to cardiovascular causes" if the effect is real. Of interest, the overall death rate was not significantly different. I did not see anything that suggested it was isolated to the Avandia plus insulin combination.

So are we sure that this is a real effect? No. We would be more certain if we had the results of a large trial designed to look specifically at this issue. And the one large trial in the metanalysis that was designed to look at cardiac outcomes did not demonstrate a difference. Proposed mechanisms are a demonstrated increase in LDL cholesterol on Avandia, and a demonstrated aggravation of congestive heart failure.

What does it mean for the individual? If you were able to acheive glucose control with Avandia that you were unable to acheive with other drugs, if your LDL cholesterol is not elevated and your heart function is normal, I don't think I'd trade the known benefit of glucose control for a questionable risk of heart attack (i.e. I'd stay on the Avandia). However, if you hadn't tried the other drugs that can be used in combination with Metformin, it would be reasonable to see if you can get the same benefit (glucose control) without the potential risk. Alternatively, there is apparently a study in progress that is designed to look at this issue called RECORD. I imagine that information from that study will be coming out shortly, or interim information may be made available because of the NEJM metanalysis. It would also be reasonable not to change anything until that new information is available.

Don't panic.

Linda

No panic--I am always a bit leery of Metastudies, myself, as the chances to cherry-pick are larger and more tempting, especially if one has an axe to grind.
The data coming out seems to be of the axe-grinding kind, but Physicians being what they are, and the legal climate being what it is in the US, my doc has switched me to another one of the drugs to work with metformin.

I had been on Avandamet before, and after I moved to Texas, the new Doc I was seeing said that I had the best blood work for a diabetic he had ever seen, and took me off the avandia part. After a couple of "woo-woo"-like events with that doc, I changed to the one I have now. He determined that the reason my blood work was so good was that Avandia actually worked, while Metformin alone didn't, I went back on Avandamet.

Since Avandia was the only one I had used with the Metformin, we will keep an eye on what this new stuff does.