TOPICS > Health

Painkiller Naproxen May Increase Heart Attack and Stroke

December 21, 2004 at 12:00 AM EDT


GWEN IFILL: Now, new concerns about an old drug. This time, the warnings target an over-the-counter medication, naproxen, marketed heavily under the brand name Aleve. Federal officials have suspended a trial studying the drug’s role in preventing Alzheimer’s Disease, after early results linked naproxen to an increased risk of heart attack and stroke. What more do consumers need to know about this and other warnings?

For that we turn to: Susan Dentzer, our health correspondent; and Dr. Elias Zerhouni, the director of the National Institutes of Health. NIH sponsored the naproxen trial.

GWEN IFILL: Susan Dentzer, how… take us back through this. How was this discovered? We were just talking about Celebrex last week. Now another one.

SUSAN DENTZER: For years, Gwen, there has been a supposition that people who took the old-fashioned kind of non-steroidal, anti-inflammatory drugs like Aleve, like ibuprofen had a lower risk of developing Alzheimer’s Disease. So people decided to test that and scientists got together and formed a large clinical trial funded by the National Institute on Aging to test that question and see whether it was proven out in fact.

So about 2,500 patients were assembled — people 70 and older at high risk of developing Alzheimer’s because they have a family history of it, and they were divided into groups, about 1,100 of those patients got dummy pills. The rest were split between patients who were taking Celebrex and patients who were taking Aleve.

Then what happened was this: Just this past week, we know we got the results of the one National Cancer Institute trial that seemed to suggest that Celebrex had a much higher risk of heart attack and stroke.

What happened was the patients in this Alzheimer’s trial, many of whom were of course on Celebrex but didn’t know it, it’s what we call a blinded trial, they didn’t know if they were on dummy pills or Celebrex, they essentially went on a pill strike and started calling up the centers they were enrolled in and saying, look, I’m not going to take these pills anymore. I think they’re dangerous.

So, that coupled with the fact that some early data was, in fact, showing that in the group that was on Aleve, there was a 50 percent higher rate of heart attacks and strokes, even though it was early data, a high enough rate that the sponsors of the trial said, you know what, we have to cut this active phase now.

They told all the patients to stop taking their pills. They’ll continue the trial going forward to see if it really does lead to any prevention of Alzheimer’s, but in fact the active phase of the trial is now over.

GWEN IFILL: If we hadn’t just heard what we heard recently about Celebrex and VIOXX, would this have happened, do you think, the same kind of findings would have been found about Aleve?

SUSAN DENTZER: Well, it was very — particularly the findings about Vioxx and the fact that Vioxx was pulled off the market that prompted everybody to go back one more time and look at the data on cardiovascular risks and say, are we really seeing increases in heart attacks and strokes and so forth, so because of those events, now people are scrutinizing all of this much more closely and finding that there does seem to be this association.

GWEN IFILL: You said there was a 50 percent higher risk of heart attack or stroke using naproxen than people who I guess were on placebos. Is that statistically significant?

SUSAN DENTZER: Well, the investigators are stopping short of calling this what we would call statistically significant because these are early results. And it’s also important to say these numbers are still small. Out of 2,500 patients in the trial, there were only 70 overall heart attack and stroke events, so it’s small numbers.

But they think that it’s a real effect. They’re going to go back and look at the data one more time, count them. The numbers may change a bit. They think there is a real effect. They certainly believe that there was enough of a risk that the active phase of the trial should be stopped.

GWEN IFILL: It doesn’t sound like they think it’s enough of a risk at this stage to actually pull the drug from the market.

SUSAN DENTZER: No, clearly not because much of the other evidence around Aleve, around naproxen points the other direction. There’s even been some supposition that it protects the heart. So on the strength of one study, which of course is not a completed study yet, it’s preliminary information, there’s not enough information yet to act one way or another.

GWEN IFILL: Dr. Zerhouni, what is NIH’S role in studies and trials like this?

DR. ELIAS ZERHOUNI: Well, our role is really to look at all potentials for drugs, in particular when we have a drug that is already approved, like Aleve or Celebrex, what we also try to do is to expand and find uses of the drug that could be of great benefit to other patients, for example, in cancer, we know that anti-inflammatories such as Celebrex could slow down or prevent the occurrence of colon cancer.

We have over 40 trials right now looking at the role of anti-inflammatory agents in preventing cancer or lowering the incidents of cancer. So we look at new uses, in particular the prevention area, where these drugs are going to be used not for the normal indications, but for daily, longer-term applications to try to prevent, for example, in this case, Alzheimer’s Disease.

GWEN IFILL: One of the big differences here is naproxen isn’t a brand-new drug. This isn’t a wonder drug we’ve just discovered about. It’s been around since, what, 1976?

DR. ELIAS ZERHOUNI: That’s correct.

GWEN IFILL: Why are we just discovering these problems now?

DR. ELIAS ZERHOUNI: Well, I think it’s two-folds. One is we’re extending really the indications for these drugs. We’re giving them to patients for longer periods of time at different dosages than those recommended in clinical practice. And we’re trying to find if, in fact, these drugs, which have been very safe, can be used for longer-term daily use for preventing diseases.

The other effect is that we have better science. More and more I think people get surprised. You know, they hear about Vioxx; they hear about Celebrex. They say, what’s going on. Well, what’s going on is that the good news is we have better ways of detecting even small amounts of risk. The bad news is that people then say, well, I’m confused and I really need to understand what to make of it.

GWEN IFILL: I want to ask you about risk in just a moment, but first I want to go back to something else you just said, which is that it’s a matter of taking these drugs over longer periods of time, which are exposing the problems. So when the doctors say, as long as you don’t take it longer than ten days, are you pretty much covered?

DR. ELIAS ZERHOUNI: Yes, I think it’s pretty clear that if you take the drugs as recommended by the FDA with the appropriate dosage for ten days or less, and if you want to use it for longer than that, you really have to have a significant benefit.

When we do research, as you know, in an Alzheimer’s trial, what we’re thinking is that there may be a potential benefit. So then when we take a decision to stop a trial, we’re taking it because there is no known benefit. A patient, on the other hand, has pain, arthritis or a significant condition for which they need the drug, so our recommendation is always, don’t overreact when you hear news like this.

First thing you should do is use the drug as it’s known uses are indicated. Don’t take more than you need. Don’t take it for longer than you need. And if you need to take it for longer, you really need to make sure that the benefit that you draw from it is worth the risk.

GWEN IFILL: Doctor, how does a layperson like myself measure benefit against the risk?

DR. ELIAS ZERHOUNI: Right. The best way to do it is, if you are dealing with an over-the-counter drug, follow the instructions. Don’t go beyond the instructions. The second is if you, on the other hand, need the drug because it has created a benefit for you, then you really need to talk to your physician and schedule tests so that any side effect can be measured and can be detected ahead of time.

GWEN IFILL: What are the other risks we should be on the lookout for? I mean you talk about non-inflammatory drugs. I think about ibuprofen and Advil and Motrin that a lot of people take probably every day.

DR. ELIAS ZERHOUNI: Well, that’s the first thing that I think we need to understand. That chronic utilization of drugs is in itself a benefit but also it contains risk. There is no drug that doesn’t have both a risk and a benefit to it. So that when we are looking at this data that now is coming to the front, we need to truly have a full analysis of all of the trials that are now available.

Remember, I think Susan was right when she said that Vioxx is what triggered NIH to look very carefully at the cardiovascular effects of all of these drugs. That’s what we’re doing. And we’re accumulating that information, sharing it with FDA, but people need to understand this is complex. And when we talk about Alzheimer’s, we’re talking about 70-year-old patients. How does that apply to a 30-year-old or 50-year-old? So we need to collate all of that information and really come to a conclusion.

GWEN IFILL: So there are studies under way which involve long-term risk of taking ibuprofen as well?

DR. ELIAS ZERHOUNI: Exactly. And there have been studies also that have been published, as Susan mentioned, some of them don’t show an increased risk for ibuprofen or naproxen. So we have to really understand all of that. But in the meantime, the public should know that overreaction is not the right thing to do. Withdrawing a drug from the market willy-nilly is not the right thing to do.

The FDA is doing a good job putting all of that information together, both from NIH, the science agency, and from the industry, and within a matter of weeks, I think we should come up with an understanding, a better understanding of what these drugs do.

GWEN IFILL: But also in the meantime, someone said to me if you are an arthritis sufferer, this has not been a good week for you. What does someone who is suffering who needs that kind of support, that needs that kind of pain relief over the long term do?

DR. ELIAS ZERHOUNI: Don’t change your treatment right now on the basis of us, NIH, stopping the trial for Alzheimer’s Disease. We’re doing it for research purposes, not for the normal uses of the drug. But if you’ve been using it at high doses for a very long time, it’s time to go talk to your physician and say, well, what do we need to do since it’s such a great benefit for me to minimize my risk.

What’s my cardiovascular risk? What is it that I may be susceptible to as a patient? Have that conversation because as a physician, I can tell you no patients is equal to the next patient. You have to assess the risk-benefit for each individual.

GWEN IFILL: Susan, let’s talk about policy implications. As we heard in the News Summary, there is an acting head of the Food and Drug Administration. These drug safety questions seem to be coming up every few days. Is there something that when Congress comes back they’re going to find right on their plate?

SUSAN DENTZER: One thing in particular is that there will be a drive to look broadly at our current drug approval and drug post-marketing surveillance process; once drugs are on the market, how carefully do we watch them for side effects and ask whether what we have now is the system that we need going forward.

And the answer pretty clearly for most people is no. What we have to do probably, many in Congress are arguing now, is adapt the system so that it takes into account the increasing complexity that we now understand to be the case from the science that Dr. Zerhouni talked about, the complex interactions that drugs have on the body and our new data collection capabilities.

All these other ways now we can capture information about what’s going on as a consequence of long-term chronic drug use that we need to know in order to keep … decide whether to keep drugs on the market or pull them off. So Congress I think is going to look very seriously at that, whether it moves forward with an actual reform remains to be seen.

DR. ELIAS ZERHOUNI: I would actually echo what Susan says. We have work to do, especially now that we have chronic diseases where people take drugs daily for a long period of time. And it is not enough to have a trial that is a few weeks long or a year long to then conclude that everything is very safe, especially with the new science that we have.

So I think we’re going to have to have a wide discussion about how do we make it possible for the FDA, for NIH, for doctors to have the information on time as we provide the medication to the population.

GWEN IFILL: Susan, the FDA also announced today some changes or at least… it wasn’t the FDA. It was a taskforce that was investigating this whole idea of drug importation. Did they come up with anything new?

SUSAN DENTZER: What they said, Gwen, was that personal importation of individuals going over the Internet, ordering drugs up that are from Canada or maybe say they’re from Canada but actually from Southeast Asia is really not safe and not a good idea and there’s no way to make it safe.

But commercial importation of drugs, wholesale importation of drugs from Canada that was done through, for example, a large wholesaler, very clear controls over the drug supply chain probably could be made safe if, in fact, the FDA was given a lot more resources to monitor it. And this, in fact, puts the challenge squarely in Congress’s lap.

As we look at that kind of question, as over and against whether we want it to pump more money into the FDA to do better post-marketing surveillance, we’re going to have some policy choices now to face as a country. Do we want to make sure our drugs supply here is safe or do we want to perhaps complicate things by bringing in drugs from other countries; that will be the issue.

GWEN IFILL: Susan Dentzer, Elias Zerhouni, thank you both very much.

SUSAN DENTZER: Thanks, Gwen.