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Celebrex and Increased Risk of Heart Disease

December 17, 2004 at 12:00 AM EDT
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JEFFREY BROWN: In September, it was Vioxx. The blockbuster painkiller drug was pulled off the market after a study showed that it doubled the risk of heart attacks and strokes. Today, there was news of potential problems with another top-selling painkiller, Celebrex.

SPOKESPERSON: Celebrate, celebrate…

JEFFREY BROWN: The heavily advertised Celebrex has been prescribed to more than 27 million Americans for conditions such as arthritis, sprains and severe menstrual cramps. Like Vioxx, it’s part of a class of drugs called cox-2 inhibitors.

The drug’s manufacturer, Pfizer, has maintained for months that numerous studies showed no cardiovascular problems like those attributable to Vioxx. But today, Pfizer announced that one study of the drug had shown an increased risk of heart attacks when the drug was taken at high doses. In a video statement today, Pfizer’s chairman and CEO, Hank McKinnell, announced that Celebrex would stay on the market.

HANK McKINNELL: We have no plans to withdraw Celebrex; what we have is a very surprising result from one of two studies, the relevance of which for the vast majority of patients benefiting from treatment with Celebrex we don’t yet fully understand.

JEFFREY BROWN: McKinnell also said Pfizer would take immediate steps to communicate results to regulators, doctors, and patients.

JEFFREY BROWN: For more on today’s developments, I’m joined by: Dr. John Reveille, Director of the Division of Rheumatology at the University of Texas, Health Science Center at Houston; and by our health correspondent, Susan Dentzer.

Susan, starting with you, the studies that led to today’s announcement were actually looking at whether Celebrex could have further benefits beyond what it’s usually prescribed for. Tell us about the tests and what they found.

SUSAN DENTZER: That’s right. These tests were looking at whether Celebrex could help prevent the recurrence of colon polyps in people who already had them. Colon polyps often translate into colon cancer. So these were cancer prevention trials.

What happened was that the National Cancer Institute officials got on the phone last night and called Pfizer and said “look, we’ve got two strange results here. In one set of studies we’re doing, the National Cancer Institute, involving more than 2,000 patients, some of them on dummy pills, some of them on higher-than-normal doses of Celebrex, we’re seeing higher rates of heart attacks and strokes — 2.5-3.4 times higher risks of heart attack and strokes.

In another trial sponsored by Pfizer looking at the same thing colon cancer prevention, roughly the same size, roughly the same duration, slightly different dose, no real statistically meaningful difference in heart attacks and strokes on the patients taking Celebrex or the patients taking dummy bills. So we’ve got a mystery here, it’s a serious enough mystery the National Cancer Institute said that we’re going to stop this trial we’re sponsoring and now it’s up to you, Pfizer, to figure out where to go from here.

JEFFREY BROWN: There’s uncertainty but given the context here, given what’s been in the air since VIOXX, the red lights went off and they decided to act quickly?

SUSAN DENTZER: That’s absolutely right.

JEFFREY BROWN: You were able to talk to an official at Pfizer today. Why are they keeping it on the market?

SUSAN DENTZER: Because for the moment this is, in fact, as the CEO said, a surprising result. Almost all the other data about Celebrex points in the opposite direction. In fact, there’s even one large study that seems to suggest that Celebrex could protect your heart. So this is an anomalous result in the great scheme of things relative to all the other studies about Celebrex.

It, of course, is… has a striking similarity to what we found out about Vioxx, which, frankly, also came about through a colon cancer prevention trial. So that is why there’s so much caution and why Pfizer says it’s going to look at it and why Food and Drug Administration said today they’re going to scrutinize it and the National Institutes of Health said it’s going to look very carefully at 40 studies that it now has under way where patients are being studied for taking Celebrex and other effects.

JEFFREY BROWN: Dr. Reveille, the company said they wanted to get the information out to doctors like yourself. Knowing what you now know, what concerns do you have, and for which patients?

DR. JOHN REVEILLE: Well, we’ve been concerned actually since the problems with Vioxx surfaced and became public in September that there was the potential for a risk for heart disease in patients taking Vioxx specifically and possibly the cox-2 inhibitor class of drugs generically. And with these findings today, that those concerns become somewhat heightened.

So where we sit right now is that in patients who already have established heart disease or at high risk for developing heart disease, specifically patients with uncontrolled high blood pressure, elevated cholesterol, or patients with diabetes, we’re going to be very cautious about prescribing these drugs, especially in the higher doses such as 400 milligrams a day that are used in patients, for example, who have rheumatoid arthritis.

JEFFREY BROWN: Well, I want to ask you about the doses just as a factual question because there seemed to be a little confusion there. Do most people… is it correct that most people now taking Celebrex are using lower doses than were used in the studies and therefore perhaps have lower risks?

DR. JOHN REVEILLE: The most commonly recommended dose for Celebrex, the most common indication is for patients who have osteoarthritis, which is the most common kind of arthritis affecting up to 40 percent of the general population. And the recommended doses are 100 milligrams of the drug twice a day. That 200 milligrams a day is below the dose that was shown to, in that one study, give a higher risk for heart disease, which is 400 to even 800 milligrams a day.

JEFFREY BROWN: So, Dr. Reveille, these are extraordinarily popular drugs. So what do you say? What do you say to the person who’s taking it now? What do they do today or tomorrow?

DR. JOHN REVEILLE: Well, I think I would sit down there, especially if the patient falls into one of those categories where they have the highest risk for developing heart disease or already have established heart disease and consider other alternatives that would be out there that perhaps would not be cox-2 inhibitors for such as taking another non-steroidal anti-inflammatory drug, say ibuprofen or naproxen perhaps if there is any problem, because remember, these drugs were released specifically or most importantly for those patients who have had gastrointestinal problems, bleeding ulcers or the like from other non-steroidal anti-inflammatory drugs.

These drugs have a lower risk of developing those things. For those kinds of patients, or patients who have heart disease, we’re looking at other alternatives, also. That’s not to say that patients should automatically all stop taking Celebrex at this point. It’s very premature to say that. But certainly in those with heart disease or highest risk for that we are being a bit more cautious, talking it over with the patient and letting them decide this versus the other alternatives out there.

JEFFREY BROWN: So, Susan, if I hear both of you right, there’s two issues here. There’s the specific drug, in this case Celebrex, and then there’s this class of drugs, which includes Vioxx, and there seems to be a lot of questions about both.

SUSAN DENTZER: Absolutely. It’s not clear what is the problem with these drugs. They’re different drugs; even though they’re in the same class they have different mechanisms. Why are they creating these problems? Are they raising blood pressure in people? What’s causing it? Also, what’s the dose that’s involved here? Is it a question where the higher the dose the greater the risk or not? And very importantly, how long do you have to be on these drugs?

In the case of Vioxx, the danger only appeared to crop up after patients had been on it a year and a half. These trials involve patients who’ve been on the drugs three years or more. So all of these things are swirling around and there are even other drugs we haven’t talked about.

JEFFREY BROWN: Dr. Reveille, what do you want to see happen next? What has to happen?

DR. JOHN REVEILLE: We definitely need to see more studies to help us understand if this is a problem with all cox-2 inhibitors because there’s another one out there, which is Bextra, or was this really having VIOXX being more or less the leading edge and this a spurious result? Whatever we ultimately find for the time being, we’re being cautious.

JEFFREY BROWN: You said earlier, Susan, that federal health agencies were starting to take further action. What specifically? What will they be doing next?

SUSAN DENTZER: They’re going to look much more closely at these data. They’re also going to have a major conference coming up in February to look at all of these drugs and decide what to do further. They may put out additional warnings on Celebrex in the interim. And they’re also taking pains to tell everybody that, you know what?

We want you to think about taking other drugs, common non- steroidal anti-inflammatory drugs like ibuprofen and Aleve, but we haven’t studies those either for their effects on cardiovascular risks. So what’s being created now is a note of caution around all of these drugs and whether all of them may have a role in creating additional heart attack and strokes.

JEFFREY BROWN: Does that sound right, Dr. Reveille, that even those very familiar drugs might have an air of mystery?

DR. JOHN REVEILLE: Absolutely. In fact, we’ve known since the early ’80s that there was cardiovascular complications associated with another very widely used non-steroidal anti- inflammatory drug called Indomethison. There were some reports back then although nothing has really surfaced since then.

JEFFREY BROWN: And Susan, there are, of course, some wide financial implications here for… certainly for Pfizer.

SUSAN DENTZER: Absolutely. Pfizer’s stock dropped 11 percent today just on this news and, of course nothing’s really happened yet other than that a lot of red flags have been raised. This is a very large selling drug for Pfizer, as Vioxx was for Merck. There’s a potential of large lawsuits, many lawsuits have already been filed even in the case of Celebrex. So it’s going to potentially have a lot of impact depending on how this story plays out.

JEFFREY BROWN: All right. Susan Dentzer and Dr. John Reveille, thanks a lot.