Steve Nissen has a way of getting everybody’s attention. And he does that with tools that in anybody else’s hands would be deadly dull. This week he captured the attention of one of the country’s most prestigious medical journals, the Food and Drug Administration, U.S. senators and members of Congress, our leading newspapers, Wall Street, class-action lawyers, and last, but hardly least millions of people who have diabetes.
Steve is formally known as Dr. Steven Nissen, chief of cardiology at one of the country’s leading cardiology establishments, the Cleveland Clinic. He is one of the country’s most prominent cardiologists, and he concentrates more and more on drug safety. His tools of choice are statistics and meta-analyses, which pool data from previous studies. He is also an expert at searching the Web.
Together with researcher Kathy Wolski, they threw the diabetes world into a tizzy with yesterday’s online publication with an article linking Avandia to a risk of heart attacks and death. The article, “Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes,” will appear in the June 14 print issue of the prestigious New England Journal of Medicine.
The analysis, based on a review of 42 clinical studies involves nearly 28,000 patients, found that Avandia raises the risk of heart attack by 43 percent. That is statistically significant (with a p value of 0.03). Avandia also increases in the risk of death from all cardiovascular causes by 64 percent, although the finding was not statisically significant (a p value of 0.06).
Patients taking Avandia had 86 heart attacks and 39 deaths. By comparison, patients in the studies who didn’t take Avandia had 72 heart attacks and 22 deaths.
These findings are especially frightening to many people with diabetes and their doctors because two-thirds of those of us with diabetes die from heart problems. “If you find a diabetes drug increases the risk of heart attacks, the consequences are so grave that it warrants urgent action,” Dr. Nissen told The Wall Street Journal.
If Avandia threatens the heart, no one knows just how it does this. But Avandia is one of a class of drugs known as peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, which has multiple effects on the body. The notorious drug Rezulin, which Warner-Lambert withdrew from the market in 2000 after it killed at least 63 people from liver and heart disease, is a class member. David Willman of The Los Angeles Times won the 2001 Pulizer Prize for investigative reporting of that scandal.
And it’s not that there aren’t alternatives. Avandia has been the nation’s No. 2 diabetes drug. American doctors wrote more than 13 million prescriptions for Avandia last year, according to data that USA Today cited in its front-page article today. Avandia sales last year were $1.7 billion in the United States, just a bit behind another drug in the same class, Actos, with $1.9 billion, according to data cites in today’s New York Times.
Actos is in the same class of drugs as Avandia and Rezulin. But strangely it seems to have a beneficial effect on the heart. Still, both Actos and Avandia were tied to a higher rate of bone fractures in women, the companies that make these drugs said earlier this year.
Avandia has been GlaxoSmithKline’s second biggest drug franchise with $3 billion in worldwide sales. But Wall Street reacted by driving down the company’s (NYSE:GSK) share price more than 7 percent yesterday. GlaxoSmithKline is the second largest pharmaceutical company in the world after Pfizer.
All of the country’s national newspapers considered the study big news. The Wall Street Journal covered it as the lead in today’s paper. The New York Times and USA Today also have it on their front pages.
Not only did Avandia and GlaxoSmithKline come under attack. But the report renewed skepticism about the Food and Drug Adminstration’s vigilance in watching out for our health.
Representative Henry Waxman immediately called for a hearing on June 6 by the House Oversight and Government Reform Committee, which he chairs. It will examine the “FDA’s role in evaluating the drug’s safety.” Invited witnesses include Dr. Nissen, FDA Commissioner Andrew C. von Eschenbach, and GlaxoSmithKline CEO Jean-Pierre Garnier.
The leaders of the Senate Committee on Finance, Max Baucus, chairman, and Charles E. Grassley, the ranking member, yesterday wrote the FDA Commissioner to request a personal briefing on the Avandia situation. They want the FDA and GlaxoSmithKline to tell them “what they knew about Avandia, when they knew it, and why they didn’t take immediate action to protect patients.”
That question is so close to the famous question that Republican Senator Howard Baker of Tennessee asked about President Nixon in the Watergate scandal that it gives me goose bumps. The question, “What did the president know and when did he know it?” was a key one leading to the President’s eventual resignation.
Senator Grassley added, “We need to know if this is another Vioxx, where the FDA sat on its hands and endangered lives.”
The link to Vioxx is a strong one. Dr. Nissen co-authored the analysis in 2001 that showed the heart risk of taking Vioxx. While the company that sold Vioxx initially played down that concern, it withdrew that drug in September 2004.
Meanwhile, the FDA issued a “safety alert on Avandia.” It says that, “Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes.”
GlaxoSmithKline also responded immediately to Dr. Nissen’s challenge. Its key claim is that, “The totality of the data show that Avandia has a comparable cardiovascular profile to other oral anti-diabetic medicines.”
The class-action attorneys are already excited by the prospects. Lawyers are already trolling for clients.
The country has learned to listen to Dr. Nissen. He was among the first doctors to raise questions about the cardiovascular safety of Vioxx, the painkiller that Merck withdrew from the market in 2004.
Dr. Nissen says that his breakthrough came when he discovered “an obscure GlaxoSmithKline website in the U.K.” The company created that site after people sued it over its antidepressant Paxil, accusing it of burying information. Dr. Nissen’s Googling turned up the site, which was a “gold mine” of studies for his meta-analysis.
Even though I search the Web all the time, I couldn’t find the obscure site. But Dr. Nissen emailed me today that the site with the treasure trove of damning Avandia data is http://ctr.gsk.co.uk/welcome.asp.
It’s not just people taking Avandia who need to be concerned about Dr. Nissen’s report. Many people are also taking Avandia in combination drugs that have different names. As I describe them on my “Diabetes Medications” webpage, they are Avandamet, which is a combination of Avandia and metformin, and Avandaryl, a combination of Avandia and glimepiride, one of the sulfonylureas.
The big question is whether you should stop taking Avandia or one of these combinations now. None of the usual establishment figures is saying to do that on your own initiative. The best advice is probably to talk it over with your doctor.
“Patients using this drug should talk to their health care provider to determine the most appropriate course of action,” says a joint statement of the American College of Cardiology, American Diabetes Association, and American Heart Association.
You can read news reports on this breaking story elsewhere at HealthCentral.com. They include “Diabetes Drug Avandia Boosts Heart Attack, Death Risk: Study,” “U.S. reviewing risks of Glaxo diabetes drug,” and “Glaxo’s Avandia raises heart-death risk: study.”
I’ve never taken Avandia or one of the combinations that include it. The only diabetes medications I’ve ever taken are one of the sulfonylureas, metformin, and now Byetta. But if I were taking anything that had Avandia in it, I would call my doctor today. Assuming that I could get through, considering how many calls he must be juggling.
This article is based on an earlier version of my article published by HealthCentral.
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