A Painful Mistake

(2 of 3)

The first hint that there might be a problem with Vioxx surfaced in 2000, just a year after the drug won FDA approval. A study that compared Vioxx with naproxen (the active ingredient in Aleve) showed that Vioxx cut gastrointestinal problems in half but increased the risk of heart attack from 0.1% to 0.4%. Those results were ambiguous, though. Was Vioxx causing the heart attacks, or was naproxen protecting the heart? Few experts fault Merck for continuing to market Vioxx on the basis of that study alone.

But the evidence didn't stop there. Subsequent studies based on reviews of large numbers of clinical records continued to show troubling indications. The final straw was a piece of research that Merck conducted. It was a particularly careful study a randomized, double-blind trial of 2,600 patients, comparing Vioxx with a placebo designed to determine whether Vioxx might prevent the formation of polyps in the colon. The study was scheduled to last three years, but two weeks ago, the panel of doctors and statisticians that was monitoring the trial's safety data informed Merck that the evidence of cardiovascular problems in the subjects taking Vioxx was clear so clear that the trial should be halted immediately. The study showed that patients who took Vioxx for more than 18 months had a small but significant risk of suffering a heart attack or stroke--1.5% for Vioxx users, compared with 0.75% for the placebo group. After a weekend spent double-checking the safety panel's data and conclusions, Merck officials told the FDA that although there was no increase in the number of deaths among those who took the drug, the company was voluntarily recalling its drug.

So what should you do if you have a bottle of Vioxx in your medicine cabinet? "For younger patients who are otherwise well, I think you can afford to wait until you talk to your doctor," says Dr. Meggan Mackay, a rheumatologist at Columbia Presbyterian Medical Center in New York City. Older patients, particularly those with a history of heart disease, should stop taking the drug immediately and consult their doctor about a new treatment. But don't throw away your bottle; Merck has promised to reimburse customers for unused medication. For more information, call 1-888-36-VIOXX.

In the meantime, don't assume you necessarily have to switch to another COX-2 inhibitor. Aspirin, ibuprofen and naproxen work just as well as the prescription drugs, provided that you are not at increased risk for bleeding, peptic ulcer or other gastrointestinal problems. (See box for more details.)

Remember also that there's more to treating arthritis pain than popping a few pills. If you have osteoarthritis (the kind that is the result of wear and tear on the joints), you can also find substantial relief just by building up the muscles that surround those joints for example, through gentle exercises like Tai Chi, yoga or walking. The point is to keep the joints moving, even if they start the day a little stiff.

More broadly, the news about Vioxx shows once again why it is so important to continue to monitor the safety of a medication even after it has been approved. Most clinical studies involve only a few thousand patients and may last less than a year enough to catch major problems. But once a drug passes muster with the FDA, it is often prescribed for millions of people. That's when more subtle side effects may emerge. Unfortunately, so-called postapproval surveillance still tends to get short shrift.