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Vioxx, Celebrex and Aleve: What's a consumer to do? Editor's note

First it was rofecoxib (Vioxx) — a drug so risky its manufacturer pulled it off the market overnight. Then the stain spread to celecoxib (Celebrex), a relative of Vioxx. Doctors can still prescribe Celebrex, but the ad campaign that made it a household name is over, at least for now.

And today it's naproxen (Aleve, others), another member of the pain medication class known collectively as nonsteroidal anti-inflammatory drugs (NSAIDS). Unlike Celebrex and Vioxx, however, Aleve is a nonprescription drug. For the past 10 years, it's held a place alongside aspirin and acetaminophen on the drugstore shelf. Will those trusted standbys be the next to fall?

To recap the relevant events: In September 2004, the manufacturers of the arthritis drug Vioxx voluntarily removed their product from the market after a large cancer-prevention study found a statistically increased risk of heart attack and stroke in study participants treated with Vioxx, as compared with a placebo. Now evidence has emerged suggesting that other anti-inflammatory drugs also may be associated with cardiovascular risk. What's a consumer to do?

As a practicing physician, I find that these are not just rhetorical questions; they have become the focus of much of my day. Patients come to the office or call with urgent questions, such as "What does this mean to me?"

To anyone concerned, I recommend this: Take a step back, relax and look at the available data. Clinical trials are difficult to perform. They yield complicated results that defy straightforward interpretation. The first step should be to ask who is enrolled in the trial and to determine how that study group does and does not resemble the general population.

For instance, are findings of increased heart attack risk in an Alzheimer's study — in which all participants are age 70 years or older — at all relevant to a 40-year-old woman with arthritis or a 55-year-old man with acute lower back pain? Can you generalize the results of a cancer-prevention trial that enrolled only people with a history of colon polyps to the larger population of individuals without colon polyps? Is it possible that the increased risks observed with Vioxx, Celebrex and Aleve were limited to people with other heart-disease risk factors, such as smoking or obesity? If so, the risk may not be the same in people without these associated factors.

It's considered a statistical no-no to perform an after-the-fact analysis — raising questions a study wasn't originally meant to address. Clinical trials are carefully designed to ensure that the groups being compared are equivalent. By making sure that treatment and placebo groups are equivalent in the respects most important to the study's purpose, variations among individuals are less likely to affect the results.

What does this have to do with the NSAID trials behind the current controversy? Maybe more people with a history of hypertension or elevated cholesterol were assigned to treatment (getting active drug) than to placebo groups. If that happened, the treatment group could have a higher rate of heart attack and stroke, but the increase couldn't really be blamed on the drug. The proposed cause-and-effect would be just as false if the groups were reversed and a greater number of high-risk people received a placebo — only then, the drug might be credited with lowering risk instead of blamed for increasing it.

Finally, if you're still confused, think about the issue of risk and benefit. It's accepted that most if not all drugs pose some risk. Doctors prescribe drugs when they believe the benefits outweigh the risks. Oftentimes this means accepting some risk when tailoring the therapy for the specific person. Doctors zero in on the option that provides the lowest risk and greatest benefit. Penicillin, for example, carries a risk of allergic reaction greater than that of a placebo. For most people, the risk is small but real — and, in the face of a raging infection, clearly outweighed by the benefits. But for people with a history of a significant penicillin allergy, the risk may be high enough to warrant using a different therapy. To make that judgment, doctors need to know about the relative risks of different forms of therapy, the groups of people who may be at highest risk and the potential alternatives.

So it is with these anti-inflammatory drugs. Their benefits are important for many people. At this point, the risks remain undefined — as do the risks of other forms of therapy. Different studies, none of them designed to look at cardiovascular risk, have produced conflicting data. Without evidence from clinical trials designed to show how Vioxx, Celebrex or Aleve might affect cardiovascular risk in the general population, doctors have to use their best clinical judgment, recognizing that there is no one-size-fits-all solution and that patient care must be individualized.

So, what's your role in all of this? If you take Vioxx, Celebrex or Aleve — or a similar drug, because the list of suspects may not yet be complete — initiate a meaningful conversation with your doctor about how the known risks stack up against the known benefits in your particular case. Only then can you and your doctor determine how the broad and evolving body of evidence relates to you.

By Mayo Clinic staff

PN00065

December 22, 2004

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