How Safe Are Your Prescription Pills?

The doctors combined the data from several studies about COX-2 inhibitors in a statistical process called meta-analysis. Then they looked to see if the information could tell them anything about heart-attack risk--something that the original trials had not been designed to explore. Such after-the-fact, or retrospective, analysis falls pretty low on the scale of scientific reliability. But sometimes it provides good clues about where problem areas may lie.

The meta-analysis, published in last week's Journal of the American Medical Association, showed that those who took COX-2 inhibitors suffered slightly more heart attacks than those who took older, aspirin-like drugs. The authors considered several explanations. Since the older drugs help prevent heart disease, the JAMA study might only be picking up the absence of a protective effect in the COX-2 inhibitors. Or the new painkillers might actually promote the creation of blood clots. Or both processes might be at work. The point, Topol says, is that "the cardiovascular effects of the [COX-2 inhibitors are] woefully understudied."

For their part, the drug manufacturers stand firmly behind their products. Merck says its own meta-analysis, which contains data that weren't included in the JAMA study, shows that Vioxx is safe for the heart. Others have focused on the study's admitted limitations, including its direct comparisons of dissimilar patient groups. Says Dr. Michael Friedman, a senior vice president of Pharmacia: "The JAMA article is based on theory, not on solid data."

So where does that leave the patient or doctor? For now, it's best to focus on what's known. If you already have heart disease, make sure it gets treated--whether or not you're taking a COX-2 inhibitor. If your blood pressure creeps up, which sometimes happens with Celebrex and Vioxx, make sure your doctor knows about it.

And be wary of side effects. Doctors have long known that the statins can trigger a rare breakdown of muscle tissue. (Stopping the drugs at the first sign of trouble usually halts the breakdown.) For some reason, patients who took Baycol--especially at higher doses or with another drug called gemfibrozil--were at greater risk. Bayer decided to drop Baycol in part because its attempts to alert doctors to those situations didn't always work. Drugs like the statins have the potential to save thousands of lives, and COX-2 inhibitors can relieve untold suffering. The trick, as always, is in figuring out how to use them wisely.

--Reported by Alice Park and Andrea Dorfman/New York and Rochelle Renford/Tampa