Increased Risk Of Heart Attack Or Heart Disease. AARON BROWN, HOST: Good evening, again, everyone. Pfizer, the drug company giant said today it was pulling all its consumer-directed ads for the pain reliever, Celebrex, in the wake of the study showing that in high doses, it may cause an increased risk of heart attack or heart disease.
First it was Vioxx. Then it was Bextra and now it is Celebrex. What Pfizer is not doing is pulling the drug completely off the shelves. It maintains it is normal or at least it works fine in normal doses, that it’s perfectly safe when it’s used as directed.
As you’ll hear as we go along tonight, not everyone agrees with that. Pfizer’s chairman, however, when we talked to him, said every study ever done, over a period of 10 years, has shown that at least where Celebrex is concerned, the drug is safe.
You’ll hear from him. You’ll hear from the critics. But first, we need to do some background on the kind of drug that we’re talking about and the tests done on it. So we begin with CNN’s Elizabeth Cohen.
ELIZABETH COHEN, CNN CORRESPONDENT: We’re all hearing just now that the drug Celebrex might cause heart problems. But Dr. Garrett Fitzgerald first noticed something might be wrong five years ago.
That’s when he saw something disturbing in his lab at the University of Pennsylvania
That’s when he saw something disturbing in his lab at the University of Pennsylvania, first in mice and then in humans. He noticed that Celebrex eased pain by blocking production of a certain type of fat, but that same kind of fat helped protect the heart.
DR. GARRETT FITZGERALD, UNIVERSITY OF PENNSYLVANIA: When you shut down this fat to alleviate pain and inflammation, you’re exposing the cardiovascular system to hazard. So it’s really a double-edged sword.
COHEN: Dr. Fitzgerald published his research and spoke about it at international conferences but he says the drug companies that make Celebrex and similar drugs called Cox 2 inhibitors, didn’t pay much attention.
FITZGERALD: We thought this was something well worth pursuing. The companies involved at the time were somewhat dismissive.
COHEN: Pfizer, which makes Celebrex, says they did take Dr. Fitzgerald’s study seriously and that many subsequent studies by other scientists showed there were no cardiovascular problems with Celebrex.
DR. GAIL CAWKWELL, PFIZER: We weighed the evidence and we found evidence both in people and in studies in animals that contradicted some of Dr. Fitzgerald’s work.
COHEN: Dr. Fitzgerald says the experience with these pain relievers is a lesson in how a blockbuster class of drugs, heralded by some as wonder drugs, could come tumbling down. Vioxx was the first of the Cox two inhibitors to have trouble. It was taken off the market in September, after studies showed it could cause heart problems.
Then last week, the “New England Journal of Medicine” published a letter from a group of researchers saying doctors should stop prescribing another Cox two called Bextra, again because of cardiovascular concerns. Days later, the National Institutes of Health released the news that people taking Celebrex were 2 1/2-times more likely to suffer a heart attack or stroke.
FITZGERALD: The entire experience with Cox two inhibitors is an example of blockbuster overreach.
COHEN: The three Cox two inhibitors earned $5.3 billion in sales last year, more than all over-the-counter pain relievers combined. Some say that’s because Celebrex, Bextra and Vioxx were some of the most highly-marketed drugs ever.
COHEN: Well, that was the middle of our Celebrex story. The moral of the story, what people say with these Cox two inhibitors, is that some researchers like Dr. Fitzgerald say that there was evidence relatively early on, when the drugs were first being marketed, that they could cause cardiovascular problems.
Even at doses that are recommended by Pfizer
And then, last week, a study from the National Cancer Institute that said, even at regular doses, even at doses that are recommended by Pfizer, that they can increase the risk of heart attacks and strokes by 2 1/2 times. And that, some people are saying raises quite a bit of concern.
That’s why, at the request of the Food and Drug Administration, Pfizer has pulled ads, ads like some of the ones you just saw in our story, have pulled those ads off the air and out of newspapers and magazines. However, the drug is still on the market. Aaron?
BROWN: OK. I’ve got one question on Celebrex. I need you to turn you to something else. OK? Viewers will hear this in a moment. But the CEO of Pfizer says that in all of the studies — studies involving 40,000 patients, not only has Celebrex not shown itself to cause cardiovascular problems, but in fact, the reverse is true. So how does that square with what you’re hearing, generally, about the problems of these Cox 2 inhibitors?
COHEN: The bottom line is that there have been so many studies on these drugs that some of this are contradictory. That’s really the only thing that can be said right now. For example, last week, we all heard about this National Cancer Institute study that showed that regular doses that could increase cardiovascular risk 2 1/2 times.
However, at the same time, Pfizer did a study that said that it didn’t increase cardiovascular risk at all. They also didn’t say that it protected the heart or that it protected you from stokes. They just said that it didn’t seem to have any effect on heart health at all. So certainly if they’re referring to a study that shows that Celebrex protects at all, that certainly wasn’t the one.
So what you have here is you have studies that contradict each other and Aaron, I’m going to look into my crystal ball, the one that you’re about to ask me about is even more contradictory. So go ahead and we can talk about that other issue.
BROWN: I hate when you do that. Now, it’s an over-the-counter drug which is the generic form of Aleve, I guess.
COHEN: Right. Aleve is an over-the-counter drug and the chemical in that is called naproxen. Naproxen is sold both as prescription and over-the-counter as Aleve and as other drugs. Now what happened today was that the Food and Drug Administration had a conference call with reporters and they said look, the National Institutes of Health has just done this study where some people were taking Celebrex.
Some people were taking naproxen, which is Aleve. And the folks who were taking naproxen, they had a 50 percent increased risk of heart attacks and stroke, a 50 percent increased risk of heart attacks and strokes, when taking Aleve which, again, the chemical in that is naproxen.
Now interestingly enough, the folks who were taking Celebrex
Now interestingly enough, the folks who were taking Celebrex, they did not have any increased risk of heart attack or stroke. They just saw the problems in that study with naproxen. Now this of course has everyone scratching their heads. How could that be? The bottom line is that the FDA is now telling consumers if you’re going to take naproxen, take it only for 10 days. Limit it to that. If you need pain relief beyond that, go talk to your doctor.
BROWN: Yeah. Elizabeth, thank you very much, Elizabeth Cohen down in Atlanta tonight.
One of the many questions raised by all of this, how did the link between all of these types of drugs, these Cox 2 inhibitors and heart attacks go unnoticed for so long? Why wasn’t the risk detected before the drugs were approved? The answer may lie, in part, in how drugs get approved.
BROWN: For a drug company to win FDA approval for a new drug, it must first outline the studies it plans to conduct to test how safe and effective the drug will be.
ALAN GOLDHAMMER, Ph.D, ASSOC VP REGULATORY AFFAIRS, PHARMA: They have to register those clinical trials with FDA and FDA must give their assent before the clinical trials are started.
BROWN: This is a crucial step, according to Dr. Jerry Avorn, a professor at Harvard Medical School and author of “Powerful Medicines.”
DR. JERRY AVORN, AUTHOR, “POWERFUL MEDICINES”: The way we learn about drug side effects has everything to do with the way the companies set up the studies before they bring the results to the FDA. And of course it’s the companies that do the studies of these drugs, not the FDA or other groups. BROWN: Dr. Avorn says how drug studies are designed may actually prevent problems from being detected. To begin with, he says, the study must last long enough.
AVORN: If you’ve got a side effect that isn’t seen until after six months of using a drug, at all of the pre-approval studies only lasted for two or three months, you could easily miss that.
BROWN: Another crucial factor who participates in the study. Are the people enrolled in a clinical trial similar to those who will actually take the medication once it’s approved and marketed? A study must also be large enough to uncover dangers. Say for every 5,000 people that take a drug, only one will develop the side effect.
AVORN: You’re going to miss that if you’re study only included 3,000 people and the side effect occurs only once in every 5,000.
BROWN: Once in every 5,000 may not seem like a lot. But when a drug is used by tens of millions of people, as Celebrex or Vioxx or Bextra have been, it’s a much different picture, with potentially thousands of people at risk of being harmed.
BROWN: Now, to the business side. Celebrex was one of the most heavily-marketed drugs in history. At least 26 million Americans have used it. It makes Pfizer a ton of money and its chairman is defending it at every turn. We talked with Pfizer CEO Henry McKinnell, late this afternoon.
BROWN: Sir, you made a decision to stop marketing Celebrex on television directly to consumers. And here’s what’s curious about that to me. If you argue and you do, that the drug taken at a normal dosage level is still safe, then why stop the marketing of it at the consumer level?
HENRY McKINNELL, CEO, PFIZER: Well, we have a complicated message around safety to deliver here. I know it’s confusing a great deal of people and we wanted to focus on communications with doctors and doctors’ communications with patients and not have that cluttered by consumer marketing.
BROWN: Does any of this give you pause about this whole area of marketing directly to consumers, whether it’s this drug or any other drug that you market to consumers on television and magazines and the rest?
McKINNELL: Well, some concern I must admit. What we’re trying to do is convince patients to see doctors. The part of the message that we probably should be emphasizing is it is your doctor who has the full information around side effects and safety and efficacy and is the best person to make a judgment of what medicine is best for you.
I think that needs to be emphasized in future direct to consumer advertising
I think that needs to be emphasized in future direct to consumer advertising. BROWN: I want to move on from this and without beating this to death. What is seems to me in these ads, whether it’s yours or others, you want me to go to the doctor and say what’s this deal with Celebrex? Or what’s this deal with fill in the blank. Not simply go see your doctor more often. That’s not an unreasonable conclusion to draw, is it?
McKINNELL: I think that’s right. And I think the part of the message that needs to be strengthened is that your doctor has full information on the benefits and risks of these products and you should discuss the best option for you with your doctor.
BROWN: Let’s move on to the drug itself for a bit. You said the other day, you take it. You argued all weekend long. And I think there’s been some supporting physicians who made the same argument, too, that taken at an appropriate consumer level, it’s a safe drug. Do you have any concern, though, that as more studies are done, on the long-term use of these Cox two inhibitors, we’re going to find that there’s simply an unacceptable risk in them, despite the undeniable benefit?
McKINNELL: Well, we need to have confidence in the safety. We cannot compromise on safety. What seems to be missing in the whole discussion is that we have extensive clinical data around both the safety and the effectiveness of Celebrex in controlled clinical studies over 10 years, involving more than 40,000 patients, which show no risk of cardiovascular damage. We also have five published studies.
And five out of the five of very large groups of patients, many in real-world settings from managed care groups, for example. Five out of five studies show no cardiovascular risk due to Celebrex. In fact the Celebrex-treated patients have less cardiovascular events than those patients receiving no treatment at all. We also have three long-term studies, two of which show no cardiovascular risk. This one study is not really consistent with everything else we know about this drug.
The one study being the one that caused you that has caused this whole uproar over the last three or four days. Do you think, by the way, just as an aside, that the uproar would be the same were it not for both Vioxx and Bextra coming under question?
McKINNELL: I think it would because so many people benefit from Celebrex, some 27 million Americans. Obviously, we need to be concerned with safety signals and this is a safety signal. What we’re saying is we need to keep this in context with what else we know. And if you have questions about the use of Celebrex, your doctor’s the best person to talk to.
BROWN: We know that going back years with Vioxx, there were I’m using this as a layperson, OK? There were some red flags. There were studies that showed heart incidents which Merck then said that really had more to do with the sort of non-aspirin effect, if you will, in the study. Have there been any studies in Celebrex that caused you to wonder, if there might be an increased chance of either heart disease, heart attack or stroke? McKINNELL: Well, actually just the opposite.
The latest of these large studies was done by Dr. David Graham, the FDA whistle- blower. He looked at 1.4 million treatments in the Kaiser database. And he found at the highest dose of Vioxx, a three times risk, versus patients who received no treatment at all. Celebrex, on the other hand, had lower risks than any of the treatment options. And even had a lower risk, 0.86, than those patients in the study that received no treatment at all.
BROWN: Just a final question before we lose you, sir. And back to the beginning. Is it possible that the money, in its considerable millions that companies like yours and other drug companies spend on marketing, consumer marketing might be better spent on R&D?
McKINNELL: We spend more money on R&D than we do on marketing. But remember, we don’t actually sell our products. All of the resources we put into quote, sales and marketing is really to make sure that physicians and patients are fully aware of all the information around the risks and benefits of the medicines we are offering. And then we leave it to the doctor and the patient to decide what is the best option for them.
BROWN: Sir, it’s good to see you. It’s I imagine a difficult few days. But you’ve been out there and I think those of us who do what I do for a living, appreciate that you’ve been out there. Thank you.
McKINNELL: Thank you, Aaron.
BROWN: Thank you, CEO of Pfizer. In a moment, we’ll consult with two doctors, Dr. Sidney Wolfe, Public Citizen, Dr. John Abramson, the author of “Overdosed America,” who may see some of this a bit differently.
BROWN: More now on Celebrex and Bextra and the rest. A moment ago, you heard Henry McKinnell, the CEO of Pfizer. Here’s a bit of what he had to say, it bears hearing again, about how drugs are sold or not, as the case may be.
McKINNELL: Remember, we don’t actually sell our products. All of the resources we put into quote sales and marketing is really to make sure that physicians and patients are fully aware of the all the information around the risks and benefits of the medicines we are offering. And then, we leave it to the doctor and the patient to decide what is the best option for them.
BROWN: To the stockholder, the idea that the drug companies don’t in fact sell drugs might seem odd. It wouldn’t be the only oddity. The system is a strange cocktail of public and private. Some of the R&D Mr. McKinnell spoke about is done on the taxpayers’ dime. Regulators leave the government and work for drug companies and vice versa.
Doctors hand out samples like candy and people are supposed to ask their doctors, without asking their doctors, about any specific drug, certainly not the one we see in the commercial.
Where’s a good doctor when we need one? We’re joined by two. Dr. Sidney Wolfe of Public Citizen’s Health Research Group and in Boston, Dr. John Abramson, the author of “Overdosed America” and it’s good to have you both with us. Dr. Wolfe, just one quickie on Celebrex before we move on. Should it be on the market today?
DR. SIDNEY WOLFE, PUBLIC CITIZEN HEALTH RESEARCH GROUP: It shouldn’t be and Pfizer’s wishful thinking that by banning the direct to consumer advertising they can convince the FDA to keep it on the market is just wishful thinking. This drug is too dangerous to be on the market. Mr. Mckinnell is at the very least misleading, at the worst lying, when he tells people that the company doesn’t sell drugs.
Right after Vioxx came off the market
Right after Vioxx came off the market, the company ran full-page ads in “The New York Times” and many other newspapers saying Vioxx is bad. Our drug is perfect good. Four years ago, an FDA physician looked at a very well-controlled, large study on Celebrex and said he was worried about the increased blood clots that were occurring with the drug.
BROWN: I’m sorry, let me get Dr. Abramson in here for a second. It is a bit I’m hesitant to say any guest on this program is disingenuous. But it was a bit disingenuous I thought to say as Mr. McKinnell said, that they’re not out there selling drugs. My goodness, you have ads for drugs where they don’t even tell you what they’re for. They’re just trying to implant the name.
DR. JOHN ABRAMSON, HARVARD MEDICAL SCHOOL: Aaron, you’re absolutely right. Not only are they selling drugs to consumers by having these ads that make people look like they’re enjoying activities that they couldn’t enjoy otherwise, when we all know that Celebrex provides no better relief from arthritis pain. But the most important thing here is how the doctors have been misled.
I think Mr. McKinnell is being a little bit dis — well, he may be exaggerating a little bit when he says that Pfizer doesn’t sell drugs. The report of the class study, which was the big study, 8,000 people with osteoarthritis, comparing Celebrex to older anti-inflammatory drugs. The results were reported in “The Journal of the American Medical Association.” That report said Celebrex when taken for six months, causes fewer GI complications than the other drugs.
But the truth is, it wasn’t a six-month study. It was a 12-month study. And the FDA had definitively rejected the company’s argument to present just six months of the study. The full 12 months of the study shows that Celebrex provides no greater GI benefit than the older, far less expensive drugs.
So now, we’ve got a cloud of cardiovascular risk hanging over this drug. What are the benefits? It’s no safer. It’s no more effective and it’s far more expensive. So it’s hard to see why fully-informed doctors and fully-informed patients would be buying $3 billion worth of this drug a year.
WOLFE: I agree…
BROWN: If I could insert one thing for people that haven’t followed it this closely. One of the arguments in favor of these drugs as opposed to aspirin or ibuprofen or whatever is they cause less stomach problems, gastrointestinal problems. I hate to sound like the doctor. Now, Dr. Wolfe, you were about to say?
WOLFE: Well, as Dr. Abramson said, we knew four years ago that this idea that Celebrex protected the stomach was false. So we now have a drug that has unique risks. It causes an increase in heart attacks. It has no unique benefit either in terms of effectiveness or in terms of GI and it’s still on the market.
We have a Web site called worstpills.org where we list 181 drugs that we think are too dangerous to use and safer alternatives. They include Vioxx, off the market now, Celebrex and Bextra, hopefully soon to come off the market and Crestor, a cholesterol drug. The problem is that neither the company, Pfizer or Merck or any of the other ones, nor the FDA are really doing an adequate job, warning or informing either patients or doctors.
The FDA has pretty much stopped enforcing the laws and regulations on misleading advertising
The FDA has pretty much stopped enforcing the laws and regulations on misleading advertising. Pfizer was caught just a few weeks ago making outrageous misleading claims on Viagra, their drug for impotence. So this is an industry that is desperate, that is doing everything possible to mislead patients and doctors and then saying we don’t sell drugs.
BROWN: Dr. Abramson, just on this question of pain relief should I just take two ibuprofen and not worry so much about it? I mean is there anything out there that is truly, significantly more effective than what I can go to the drugstore and buy?
ABRAMSON: No. There isn’t Aaron. In fact, the new drug application for Celebrex. Celebrex was tested against two Advil tablets, exactly what you’re saying, for dental pain. And two Advil tablets provided significantly better relief than all doses of Celebrex that were tried. So actually you’re two Advil tablets are superior in terms of providing pain relief.
BROWN:Is the industry so big and so powerful at this point that it can get away with it sounds a little more nefarious than I mean. But that can get away with it? Is that right?
WOLFE: I think that’s true. In Washington, there are more drug industry lobbyists in Washington over 600, than there are members in Congress. They push the Congress away with lobbyists, with campaign contributions and so forth. And the FDA, which is technically part of the Public Health Service, is getting hundreds of millions of dollars in cash directly from the industry, to help them regulate drugs. What it does help them do is be kinder to the industry. Kindness on the part of the FDA to the drug industry, translates into increased risk to patients though.
BROWN: Let me give, Dr. Abramson the last word. We were chatting just before we went on the air. This — a lot of things that happened in a short period of time with Vioxx, Bextra and Celebrex. Are we at one of those moments, where policy may, in fact, be changed or will it do you think just pass?
ABRAMSON: No, I think we’re there, Aaron. I didn’t think we were going to get there when it was just Vioxx. But I think now with Celebrex, people are starting to get the idea that the real crisis in American medicine is that even the most disciplined, dedicated doctors, can no longer get accurate information. Because the drug companies have so much influence over what we believe the best medical care is. I think the American public is now getting the picture. And this problem is fundamentally not a scientific problem. It’s a political problem.
BROWN: Gentlemen, good to have you with us. We appreciate your time. Have good holidays. Thank you.
Need Legal Help Regarding Celebrex Advertising?
New York City, Long Island, New Jersey, and Florida
Our New York personal injury lawyers are here to help you when you need it the most.