Comments on: Does Avandia cause heart attacks, and why the RECORD study is important http://www.kevinmd.com/blog/2009/06/does-avandia-cause-heart-attacks-and-why-the-record-study-is-important.html medical blog Sun, 22 Nov 2009 19:59:44 -0500 http://wordpress.org/?v=2.8.4 hourly 1 By: Dr. Matthew Mintz http://www.kevinmd.com/blog/2009/06/does-avandia-cause-heart-attacks-and-why-the-record-study-is-important.html/comment-page-1#comment-92045 Dr. Matthew Mintz Wed, 10 Jun 2009 01:39:58 +0000 http://www.kevinmd.com/blog/?p=30226#comment-92045 RECORD was not flawed from the start because it was not designed to look at heart attacks specifically. No one had even thought of heart attacks being a problem with Avandia. If anything, Avandia should have prevented heart attacks. This is why when the FDA saw GSK's data (which didn't make any sense) they decided to not make any rash decisions until studies like ADOPT, DREAM and RECORD were done. However, Nissen (who likely got a tip from inside the FDA) decided to publish the results anyway. The new study that the FDA asked GSK to do was designed to specifically look at heart attacks. This is wasted money I believe since every other available study seems to refute the Nissen article. Regarding how many people remained on Avandia, Forbes found out this answer: at the end of the study, 1,344 patients or 61% of the Avandia group were still on the drug, while 1,131 patients, or or 51% of the control group, remained on their medicines. Also, since this is a safety study and not an efficacy study, who remained on the drugs is not as much a factor since you are looking at patient exposure of a drug and not whether they stopped taking it. It is disappointing that no benefit was shown. My suspicion is that Avandia (and other TZD's) prevent heart attacks by preventing the buildup (and possible slightly reducing) of atherosclerosis in the coronary arteries. In order to show a benefit, it probably takes longer than 5 years. Recall that the benefit of glycemic control on heart attacks specifically was not shown until 30 years after the study was started. Finally, even if rosiglitazone shows no benefit on reducing heart attacks, it reduces the need for insulin as well as associated hypoglycemia. This is a major win, since most diabetic patients would prefer a pill to insulin RECORD was not flawed from the start because it was not designed to look at heart attacks specifically. No one had even thought of heart attacks being a problem with Avandia. If anything, Avandia should have prevented heart attacks. This is why when the FDA saw GSK’s data (which didn’t make any sense) they decided to not make any rash decisions until studies like ADOPT, DREAM and RECORD were done. However, Nissen (who likely got a tip from inside the FDA) decided to publish the results anyway. The new study that the FDA asked GSK to do was designed to specifically look at heart attacks. This is wasted money I believe since every other available study seems to refute the Nissen article.
Regarding how many people remained on Avandia, Forbes found out this answer: at the end of the study, 1,344 patients or 61% of the Avandia group were still on the drug, while 1,131 patients, or or 51% of the control group, remained on their medicines. Also, since this is a safety study and not an efficacy study, who remained on the drugs is not as much a factor since you are looking at patient exposure of a drug and not whether they stopped taking it.
It is disappointing that no benefit was shown. My suspicion is that Avandia (and other TZD’s) prevent heart attacks by preventing the buildup (and possible slightly reducing) of atherosclerosis in the coronary arteries. In order to show a benefit, it probably takes longer than 5 years. Recall that the benefit of glycemic control on heart attacks specifically was not shown until 30 years after the study was started.
Finally, even if rosiglitazone shows no benefit on reducing heart attacks, it reduces the need for insulin as well as associated hypoglycemia. This is a major win, since most diabetic patients would prefer a pill to insulin

]]> By: Dr. Mehmet Karaca http://www.kevinmd.com/blog/2009/06/does-avandia-cause-heart-attacks-and-why-the-record-study-is-important.html/comment-page-1#comment-91916 Dr. Mehmet Karaca Sun, 07 Jun 2009 18:45:36 +0000 http://www.kevinmd.com/blog/?p=30226#comment-91916 The RECORD study design was flawed from the get go. Wasn’t that why the FDA asked GlaxoSmithKlein, who sponsored the trial, to conduct another study to overcome the study’s limitations? One should stop and think if a company sponsored trial cannot produce favorable results for their product. Having said that even by when the 2007 interim numbers were released about 30% of participants on the rosiglitazone arm were already off the medication. Neither The Lancet paper nor the accompanying shindig at the American Diabetes Association meeting revealed how many people were still on rosiglitazone by the end of the study. If rosiglitazone is really precipitating the development of overt heart-failure in susceptible individuals as suggested by the RECORD results, isn’t it enough for us to stop prescribing this medication. It is also interesting that the medication has been shown to have a neutral effect on the risk of myocardial infarction. Why would a molecule whose sole job is to optimize glycemia and hence improve risk have a neutral effect on myocardial infarction? Isn’t it at least supposed to show an effect towards the decrease risk? To me, it does not make any ethical sense to say to a patient “well, this medication may double your risk of developing congestive heart failure but guess what you won’t die from it.” Interestingly this is the message being pushed out by this campaign of trying to rescue Avandia which appears to be hanging by a thread. If you check you regular news sources today and conduct a search for rosiglitazone and RECORD you’ll see that the news articles returned will mostly be titled something like “Rosiglitazone does not increase CV risk,” or “Rosiglitazone safe for the heart.” Really? I mean really? I think I’ll stick by January 2008 consensus statement released by ADA and cautiously prescribe pioglitazone until the air is cleared. The RECORD study design was flawed from the get go. Wasn’t that why the FDA asked GlaxoSmithKlein, who sponsored the trial, to conduct another study to overcome the study’s limitations?

One should stop and think if a company sponsored trial cannot produce favorable results for their product.

Having said that even by when the 2007 interim numbers were released about 30% of participants on the rosiglitazone arm were already off the medication. Neither The Lancet paper nor the accompanying shindig at the American Diabetes Association meeting revealed how many people were still on rosiglitazone by the end of the study.

If rosiglitazone is really precipitating the development of overt heart-failure in susceptible individuals as suggested by the RECORD results, isn’t it enough for us to stop prescribing this medication.

It is also interesting that the medication has been shown to have a neutral effect on the risk of myocardial infarction. Why would a molecule whose sole job is to optimize glycemia and hence improve risk have a neutral effect on myocardial infarction? Isn’t it at least supposed to show an effect towards the decrease risk?

To me, it does not make any ethical sense to say to a patient “well, this medication may double your risk of developing congestive heart failure but guess what you won’t die from it.” Interestingly this is the message being pushed out by this campaign of trying to rescue Avandia which appears to be hanging by a thread. If you check you regular news sources today and conduct a search for rosiglitazone and RECORD you’ll see that the news articles returned will mostly be titled something like “Rosiglitazone does not increase CV risk,” or “Rosiglitazone safe for the heart.” Really? I mean really?

I think I’ll stick by January 2008 consensus statement released by ADA and cautiously prescribe pioglitazone until the air is cleared.

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