Comments on: Steven Nissen was wrong about Avandia http://www.kevinmd.com/blog/2008/06/steven-nissen-was-wrong-about-avandia.html Tue, 14 Feb 2012 19:56:00 +0000 hourly 1 By: Dr. Matthew Mintzhttp://www.kevinmd.com/blog/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86188 Dr. Matthew Mintz Thu, 12 Jun 2008 13:27:00 +0000 http://clients.emmense.com/kevinmd/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86188 Marilyn<br/>You will note that one of the critics in the medpagetoday.com article you reference is Dr. Nissen himself. <br/>You are correct in that a single post-hoc analysis by itself does not prove conclusively that there is absolutely no chance of risk. However, in response to the Nissen publication, large, randomized prospective trials were analyzed by the FDA (RECORD, ADOPT, DREAM) and the invesitgators of ongoing trials using Avandia (ACCORD, VADT) to make sure there wasn't a problem. All of these analysis found no increase risk fo heart attacks. The only way to know for sure is a large, prospective trial to answer the question specifically. This is what RECORD was designed to do. In response to Nissen, the RECORD investigators published an interim analysis of there ongoing study, and also found no problems. The final RECORD results should be presented in a couple of years. Fortunately for patients, but unfortunately in terms of answering the question, because (like ACCORD, ADVANCE and VADT) the number of heart attacks has been substantially lower than expected, even the final results of RECORD may not have the statistical power to prove the point. That said, if there really is a 43% increase risk of heart attacks with Avandia as Nissen claimed, we would have probably picked up some signal in the over 15,000 patients studied for over 3.5 years. Marilyn
You will note that one of the critics in the medpagetoday.com article you reference is Dr. Nissen himself.
You are correct in that a single post-hoc analysis by itself does not prove conclusively that there is absolutely no chance of risk. However, in response to the Nissen publication, large, randomized prospective trials were analyzed by the FDA (RECORD, ADOPT, DREAM) and the invesitgators of ongoing trials using Avandia (ACCORD, VADT) to make sure there wasn’t a problem. All of these analysis found no increase risk fo heart attacks. The only way to know for sure is a large, prospective trial to answer the question specifically. This is what RECORD was designed to do. In response to Nissen, the RECORD investigators published an interim analysis of there ongoing study, and also found no problems. The final RECORD results should be presented in a couple of years. Fortunately for patients, but unfortunately in terms of answering the question, because (like ACCORD, ADVANCE and VADT) the number of heart attacks has been substantially lower than expected, even the final results of RECORD may not have the statistical power to prove the point. That said, if there really is a 43% increase risk of heart attacks with Avandia as Nissen claimed, we would have probably picked up some signal in the over 15,000 patients studied for over 3.5 years.

]]> By: Dr. Matthew Mintzhttp://www.kevinmd.com/blog/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86187 Dr. Matthew Mintz Thu, 12 Jun 2008 12:52:00 +0000 http://clients.emmense.com/kevinmd/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86187 Martin,<br/>Avandia (rosiglitazone) and Actos (pioglitazone) -also known as Thiazolidinediones or TZDs- are associated with heart failure. This is not necessarily the same thing a causing it. This adverse effect with the TZD's is well known, and the mechanism is understood: by increasing fluid retention in patients with an already weakened heart, TZD's can put those patients into heart failure. Heart failure is "bad," but the risk is low and can usually be avoided if TZD's are used cautiously or avoided in patients at risk. <br/>This adverse effect was well known long before Nissen's publication. Myocardial infarction and ischemia are completely different than heart failure (pipe problem vs. pump problem) and there is no biologically plausable reason that TZD's would cause this. In fact, most data (PROACTIVE, PERISCOPE, CHICAGO, VICTORY, and even ACCORD and ADVANCE) suggest that if anything, the TZD's may actually prevent myocardial ischemia and infarction (heart attacks). <br/>The Nissen meta-analysis was a statistical quirk that got published a little too quickly, generated a lot of attention (media, congress), scared a lot of patients (and some physicians), and in light of older and more recent data, was simply incorrect. Martin,
Avandia (rosiglitazone) and Actos (pioglitazone) -also known as Thiazolidinediones or TZDs- are associated with heart failure. This is not necessarily the same thing a causing it. This adverse effect with the TZD’s is well known, and the mechanism is understood: by increasing fluid retention in patients with an already weakened heart, TZD’s can put those patients into heart failure. Heart failure is “bad,” but the risk is low and can usually be avoided if TZD’s are used cautiously or avoided in patients at risk.
This adverse effect was well known long before Nissen’s publication. Myocardial infarction and ischemia are completely different than heart failure (pipe problem vs. pump problem) and there is no biologically plausable reason that TZD’s would cause this. In fact, most data (PROACTIVE, PERISCOPE, CHICAGO, VICTORY, and even ACCORD and ADVANCE) suggest that if anything, the TZD’s may actually prevent myocardial ischemia and infarction (heart attacks).
The Nissen meta-analysis was a statistical quirk that got published a little too quickly, generated a lot of attention (media, congress), scared a lot of patients (and some physicians), and in light of older and more recent data, was simply incorrect.

]]> By: Anonymoushttp://www.kevinmd.com/blog/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86186 Anonymous Thu, 12 Jun 2008 12:41:00 +0000 http://clients.emmense.com/kevinmd/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86186 In these studies, patients were not randomized to Avandia and the studies were not designed to test Avandia's effect on cardiovascular outcomes. These analyses amount to post-hoc data-dredging. <br/><br/>See this article for further information:<br/><br/>http://www.medpagetoday.com/Endocrinology/Diabetes/tb/9769<br/><br/>Marilyn Mann In these studies, patients were not randomized to Avandia and the studies were not designed to test Avandia’s effect on cardiovascular outcomes. These analyses amount to post-hoc data-dredging.

See this article for further information:

http://www.medpagetoday.com/Endocrinology/Diabetes/tb/9769

Marilyn Mann

]]> By: Martinhttp://www.kevinmd.com/blog/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86185 Martin Thu, 12 Jun 2008 11:12:00 +0000 http://clients.emmense.com/kevinmd/2008/06/steven-nissen-was-wrong-about-avandia.html#comment-86185 Yet it causes heart failure - and that's bad enough. Yet it causes heart failure – and that’s bad enough.

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