More than 6 million people around the world have taken the drug Avandia (rosiglitazone) to treat Type II diabetes. But a new study published this week in The New England Journal of Medicine suggests that the drug is linked to a higher risk of heart attack and death. In the study, Dr. Steven Nissen and Kathy Wolski of the Cleveland Clinic analyzed the results of 42 existing trials and found that Avandia increased heart-attack risk 43 percent. In response to the study, the Food and Drug Administration (FDA) issued a safety alert advising patients to talk to their doctors about whether they should continue taking the medication. Three major medical groups—the American Heart Association, the American College of Cardiology and the American Diabetes Association—also issued a joint advisory urging patients to call their doctors. "We don't feel this is an emergency or a crisis," says Dr. Sue Kirkman, vice president, clinical affairs, at the American Diabetes Association. Although it has been known for some time that drugs in the same class as Avandia increase the chances of developing congestive heart failure, the heart-attack risk is news, Kirkman says. However, she cautions, further analysis is needed to determine the severity of the risk. In a statement, Avandia's manufacturer, GlaxoSmithKline, defended Avandia’s safety, claiming that the study is based on "incomplete evidence." Nissen spoke to NEWSWEEK's Barbara Kantrowitz about his research. Excerpts:
NEWSWEEK: What should patients take away from your study?
Dr. Steven Nissen: The most important thing is no patient should stop taking any medication on their own. We hope that diabetes specialists and other generalists who prescribe diabetic drugs like Avandia will read our manuscript, will carefully review the risks that we’ve outlined and will then confer with patients about what the best therapy should be. It’s important that patients not panic, that they talk to their doctor.
Should patients who are on this drug call their doctor today?
Well, within a few days. We don’t need a public panic. What we need is a controlled response.
Is there a case for prescribing Avandia? Are there some patients for whom the benefits outweigh the risks?
Again, I don’t think I want to go there. It’s important for me as a physician-scientist to put the data out there in a very neutral fashion, and not cast judgment about what people ought to do. We’re going to let everybody read our paper and make up their own minds. Obviously the FDA read our paper because they just issued a safety alert.
Why is the potential increase in heart-disease risk so serious for diabetics?
Between 65 and 80 percent of all the deaths in diabetes are due to cardiovascular disease. A drug that increases the risk of heart disease in diabetics has truly profound public health consequences.
The manufacturer, GlaxoSmithKline, has issued a statement saying that they strongly disagree with your conclusions. What’s your response to that?
I’m not going to engage in a war of words with the company. I’m an independent physician-scientist. I call ‘em the way I see ‘em. They’re certainly welcome to offer their opinion, but I’m really not going to debate the issue with them.
What about criticism of your study that it’s a meta-analysis?
We completely agree. We were using publicly available data, not original source data. We used the information that was available. Obviously it’s not as good as having all of the original data. But we stand behind our findings. We believe in the long run, they will hold up very well.
A lot of your paper is about the FDA approval process. What reforms do you think are necessary?
There are concerns about the approval process. This drug was approved because it lowered blood sugar. There was some evidence at the time of the initial approval that the cardiovascular events were going in the wrong direction. Now eight years later, we haven’t had a definitive cardiovascular outcomes trial. And so with that early signal, we didn’t get good follow-up. There are people who believe that the post-marketing surveillance system needs to be fixed, that it doesn’t do a good job of picking up these kinds of risks. I think that will have a lot of traction now and I’m sure you will see hearings on the House and Senate sides. There’s legislation under consideration now to try and fix this system.
So, there are problems with the approval process. There are problems with the post-marketing system. We’ve got to find a way to prevent these kinds of disasters in the future.
For patients who are diabetics, do you think they should feel confident that other drugs out there are safer choices?
I can tell you this, there is a drug known as pioglitazone or Actos, and the drug so far has shown, if anything, evidence of improving cardiovascular risk. So that’s good. Obviously, everything has to be looked at in totality.
Beyond Avandia, what advice would you give patients about taking any new medication prescribed by their doctor?
There is no question that we need to regain the confidence of patients. I’d like to believe that we can improve the regulatory process so that patients can once again feel confident in the drugs that they take. It really is a shame that we have lost the confidence of the public in our ability to do this correctly.
Are there questions that patients should be asking when they are prescribed a new medication?
I certainly think they should ask how long the drug has been on the market and what’s known about its safety. I think an informed patient is always better. I like it when my patients ask me those kinds of questions. But it's up to physicians and of course the FDA to do everything we can to protect patients from these kinds of drug-safety problems.
When patients ask those problems is there any red-flag answer?
It’s tough. It’s all about individual choices, individual risks and individual drugs. There’s no one answer that I can give you.