Vioxx in high doses causes hypertension

The evidence is growing: chronic, high-dose consumption of the arthritis pain reliever Vioxx can raise blood pressure and the risk of serious heart problems.

Yet a "substantial number" of patients continue to be prescribed high doses of the drug, according to researchers at Vanderbilt University Medical Center.

The researchers counted the number of prescriptions for non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, Celebrex and Vioxx, given to participants over age 49 in Tennessee's Medicaid program, called TennCare.

Of 40,000 participants who had prescriptions for any NSAID as of July 1, 2001, nearly 10,000 were taking Vioxx, and more than 1,000 of them were "high-dose" Vioxx users, with 30-day supplies of 50-milligram pills. Half that amount - 25 milligrams a day - is the recommended dose for long-term use.

The 50-milligram dose has not been shown to be more effective than lower doses of the drug in relieving chronic pain, and it has been linked to an increased risk of heart attacks. "Such use should be discouraged," the researchers concluded in the June issue of the journal Pharmacoepidemiology and Drug Safety.

Vioxx (the brand name for rofecoxib) and Celebrex (celecoxib) are selective COX-2 inhibitors. They relieve inflammation by blocking the cyclooxygenase-2 enzyme, but they don't inhibit the related COX-1 enzyme, which protects the stomach lining. Therefore they don't irritate the stomach as much as NSAIDs that block both enzymes.

"They cause fewer ulcers," explained the study's lead author, Marie R. Griffin, M.D., MPH, professor of Preventive Medicine and Medicine. "That's a good thing in many ways, although there's a lot of people using them who are pretty low risk for GI (gastrointestinal) events." COX-2 inhibitors also cost $80 to $100 per month, compared to about $10 to $15 for a month's supply of generic naproxen.

"We think that the rationale is that if 25 milligrams works well, then 50 milligrams is going to work better," Griffin said. "But when you look at the scant data that's out there for chronic pain, there's been no study that shows that 50 is better than 25.

"This is really common with a lot of drugs, that there's a ceiling on the effective dose - But unfortunately, there's usually not a ceiling on the side effects."

Griffin and her colleagues, who include Wayne A. Ray, Ph.D., professor of Preventive Medicine, and C. Michael Stein, M.D., professor of Medicine, have been sounding the alarm about high-dose Vioxx use since 2002.

In a study of TennCare participants published in the journal Lancet that year, the researchers reported patients on high doses of Vioxx had nearly twice the rate of serious heart problems, including heart attacks and heart-related deaths, compared to patients not on the drug.