welcome!
New to Close Concerns?
Subscribe
Already registered?
Log in
WHAT WE DO
consulting
strategic advice and comprehensive information for those interested in the diabetes industry
diabetes close up
our monthly newsletter
industry reports
periodically we take the long view on trends or on specific breakthroughs.
TEAM
Interview with Dr. Steven Nissen: Thoughts from an industry watchdog
Dr. Steven Nissen is a highly regarded coronary artery disease researcher and a vigilant activist in public health policy matters. He is currently the chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic and was previously the president of the American College of Cardiology. Earlier this year, Dr. Nissen caused a firestorm when he published a study indicating that Avandia may increase the risk of having a heart attack. Dr. Nissen is no stranger to controversy: his expressed concerns that Vioxx might cause blood clots contributed to Merck s decision to withdraw the drug in 2004. This year, Dr. Nissen was named one of the "100 Most Influential People" by Time magazine.
In an interview with diaTribe Editor in Chief, Kelly Close, Dr. Nissen talks about his view of the climate of diabetes care in the United States today and about the Avandia controversy of late. After reading our interview with Dr. Nissen, it may be helpful to read our Learning Curve about Avandia and the TZD class of drugs.
Kelly Close: Thank you so much for taking the time to speak with diaTribe, Dr. Nissen! It s a real pleasure for us. To start with, we re curious about how, as a cardiologist, you first became interested in studying PPARs (the main biological target of drugs in the TZD class).
Dr. Steven Nissen: Well, it actually goes back quite a long ways. I was aware from the very beginning that there were a lot of issues with PPAR drugs, which affect a very large number of genes. We don t know what most of those genes do. Whenever you see a drug like that, you always worry about off-target effects that the drug was not designed to produce. My concerns accelerated in September of 2005 when muraglitazar came before the FDA for approval.
I did not attend the hearing, but I did have an interest in the class of drug. The night before the hearing, I looked at the FDA s briefing documents and immediately saw that there was a rather large excess of adverse cardiovascular events in the patients who received muraglitazar. And they were serious events: death, stroke, heart attack, that sort of event. So I assumed that the FDA advisory panel would recommend unanimously that muraglitazar not be approved.
As you may recall, they actually voted 8 to 1 to approve the drug. I was just shocked. I immediately went into action and took the data from that FDA advisory panel, analyzed it independently with my statistician, and published in JAMA a few weeks later that the drug was doubling the risk of the really serious cardiovascular consequences of diabetes.
Then in September of last year, the DREAM trial was published, and if you will excuse the pun, the DREAM trial was a nightmare. There was a drug, rosiglitazone (Avandia), which reduced the incidence of new-onset diabetes by 60 or 70 percent. But all of the cardiovascular events were going in the wrong direction.
You want to prevent diabetes to avoid the complications of diabetes, the most important of which is heart disease. Eighty percent of all diabetics will die of cardiovascular disease, so this was very troubling.
Then the ADOPT trial was published, and the same thing happened. It showed a 33 percent excess of major adverse cardiovascular events. Now the really big shocker was that just as I was getting ready to publish the manuscript, I learned that GlaxoSmithKline, the maker of the drug, had actually done its own analyses beginning in September of 2005. They actually submitted to the FDA that their own analysis showed a statistically significant 31 percent increase in myocardial ischemic events (heart attacks). They d informed the FDA of this risk. But neither the FDA nor the company informed any of the rest of us. I personally believe in the right of patients and providers to know the totality of information on the benefits and risks of drugs.
Kelly: What do you think it says about endocrinology that it took a very noted cardiologist to intervene in this matter?