Your Health: Vioxx advantages overstated

Seduced by hundreds of millions of dollars in advertising, Americans -- including 22 million people with arthritis -- spend $6 billion a year for Vioxx and Celebrex, which are said to be as good as or better than standard painkillers -- and easier on the stomach. But Vioxx in particular has not lived up to the hype. Linked with serious side effects, most notably an increased risk of heart attacks, its manufacturer, Merck & Co., has been sued repeatedly. While chemically similar, Celebrex by Pfizer has not been tied to increased heart attack risk.

And neither drug fights pain better than over-the-counter medications, though they cost six times as much. At CVS, a month's supply of ibuprofen at the doses people with arthritis normally take costs $17.55; a comparable supply of Celebrex costs $107.99, and Vioxx, $110.99. Vioxx and Celebrex, like their lesser-known cousins Bextra and Mobic, are in a relatively new class of drugs called COX-2 inhibitors. Despite the hype, "there is no proof that these COX-2 drugs are better for arthritis pain than traditional ibuprofen, and there is also no proof, except for a certain subset of patients, that these drugs are safer," said Dr. Neil Minkoff, medical director of pharmacy at Harvard Pilgrim Health Care, which insures 800,000 people in Massachusetts, New Hampshire and Maine. For those reasons, some insurers, including Harvard Pilgrim, now insist that doctors get "prior approval" before writing prescriptions for them.

Touted for their stomach-protecting properties, the COX-2 inhibitors in reality "don't eliminate gastrointestinal side effects, they just reduce them, and even that is more problematic than first thought," said Dr. Jerry Avorn, chief of pharmacoepidemiology and pharmacoeconomics at Brigham and Women's Hospital in Boston. He is the author of the forthcoming book, "Powerful Medicine," on the subject.

Back in the late 1990s, when the hype over Vioxx and Celebrex began, the excitement seemed well-founded. Researchers had long known that prostaglandins, natural chemicals that are made in cells under the direction of enzymes called cyclooxygenases, were the root cause of pain and inflammation. But it turned out there were actually two types of cyclooxygenases, dubbed COX-1 and COX-2. COX-1 releases "good" prostaglandins that protect the stomach. COX-2 releases "bad" prostaglandins that further drive inflammation. The new drugs were hailed for their ability to block only COX-2 and leave the good prostaglandins intact, something that traditional NSAIDS (non-steroidal anti-inflammatory drugs) like ibuprofen could not do. Eager to get the pain-killing benefits without stomach-killing side effects, such as bleeding ulcers of traditional NSAIDs (non-steroidal anti-inflammatory drugs), doctors and patients flocked to the new drugs. Then the bad news began trickling out.

In September 2000, a study called CLASS on 8,000 patients was published in the Journal of the American Medical Association. It showed that people taking Celebrex had fewer ulcers than those taking traditional NSAIDs. But the study focused only on figures from six months of drug use. When a later analysis by the U.S. Food and Drug Administration (FDA) looked at 12 months' worth of data, this apparent advantage disappeared, said Dr. Michael Wolfe, chief of gastroenterology at Boston Medical Center.

Dr. Gail Cawkwell, worldwide medical team leader for Pfizer, said that for statistical reasons, the six-month data was felt to be "the most appropriate" to analyze. In November 2000, a study called VIGOR was published in the New England Journal of Medicine. It showed that 50 milligrams a day of Vioxx reduced the risk of serious stomach problems by half, compared to prescription strength naproxen (Aleve). But it also showed, to researchers' surprise, that the risk of heart attack was two to four times higher on Vioxx.

A Tennessee study published in the Lancet in October 2002 showed an increased heart disease risk with higher doses of Vioxx. On the other hand, a paper in Circulation in 2001 showed no excess heart disease risk of Vioxx compared with naproxen. This past May, Canadian researchers conducting an observational study wrote in the Lancet that people taking Vioxx were 80 percent likelier to be hospitalized for congestive heart failure than those taking Celebrex. Also this spring, researchers from Brigham and Women's Hospital, writing in the journal Circulation concluded that taking higher doses of Vioxx was linked to a 24 percent increase in heart attack risk. The risk occurs primarily in the first 90 days of use. Consumers and shareholders, not surprisingly, have not been thrilled about all this.

Pfizer would not confirm or deny possible litigation over Celebrex, but Merck is clearly on the defensive. In 2001, the FDA issued a "warning letter" about the company's promotional activities for Vioxx, which the agency said were "false, lacking in fair balance or otherwise misleading." The company says it has corrected the problem. Since 2002, Merck has also included heart risk data from three studies in its package labeling, said company spokeswoman Mary Elizabeth Blake.

But in New Orleans, Lewis Kahn, of the Kahn Gauthier Law Group, is leading a shareholders' proposed class action suit against Merck alleging that the company artificially inflated its stock prices based upon false and misleading statements about the safety of Vioxx. In Atlantic City, N.J, a class action suit was filed by a union pension fund alleging that it and other funds were lured into paying for the Vioxx by false marketing. In New Jersey, more than 100 people have filed personal injury lawsuits claiming that Merck failed to warn consumers about Vioxx' heart attack and other risks, said Dave Buchanan, an attorney from Seeger Weiss in Newark. In Los Angeles, Thomas Girardi of Girardi & Keese has also brought 100 personal injury claims on Vioxx. It was not clear whether similar cases have been filed in Massachusetts.

So where does this leave us? Dr. Lee Simon, a rheumatologist at Beth Israel Deaconess Medical Center in Boston, said that people should realize that while it's not wise to take 50 milligram doses of Vioxx for more than a week, there is no evidence of heart problems at the lower doses -- 12.5 and 25 milligrams a day. So, don't panic. That said, if you'd prefer standard NSAIDs such as ibuprofen, ask your doctor about additional medications to protect your stomach.