Vioxx Clinical Issues

The US FDA approved Vioxx (rofecoxib) on May 21, 1999 for the treatment of painful menstruation, acute pain in adults and for the relief of the signs and symptoms of osteoarthritis. Like its cousins, aspirin, ibuprofen and naproxen, Vioxx is a non-steroidal anti-inflammatory drug (NSAID).

But, unlike these conventional NSAIDs which block both COX-1 and COX-2 enzymes, Vioxx and the other coxibs only inhibit COX-2, the enzyme involved in pain and inflammation. Vioxx does not block the ubiquitous COX-1 enzyme which protects the stomach lining and is, therefore, thought to be gentler on the digestive tract than the older NSAIDs, which can cause ulcers and bleeding in some individuals.

The claim that COX-2 inhibitors or coxibs are less likely to cause bleeding and other digestive tract complications became their selling point – despite the fact that no one has ever said that they are more effective than classic NSAIDs in reducing pain and that only less than 10 percent of the population gets stomach damage from the older drugs. Nevertheless, under the influence of the drug companies, physicians switched patients from drugs costing eight cents a day to the $1 to $3 coxibs.

Now, with the accumulating data pointing to Vioxx’s increased risk of cardiovascular injury, researchers hypothesize that COX-2 inhibitors suppress a protein responsible for the health of blood vessels and could promote the clotting that causes heart attacks and strokes as a result. Additionally, COX-2 blockers raise blood pressure.

Although results of studies involving other COX-2 inhibitors, such as Celebrex (celecoxib), seem to suggest that these competitors
may be safer, researchers now speculate that drugs in the same class as Vioxx may appear to be safe because the FDA has not yet required the randomized, controlled trials necessary for definitive answers. Clearly, scientists and researchers worldwide are focused on the cardiovascular safety of the entire class of COX-2 inhibitors.

Since its introduction in 1999, Vioxx’s indications for use have expanded to include relief for the signs and symptoms of rheumatoid arthritis in adults; relief of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis in patients two years and older; and for the acute treatment of migraine attacks. However, as its uses expanded, data accumulated to show an increased risk of cardiovascular events with the use of Vioxx. On November 2, 2004, FDA posted on its website an early version of a recently completed observational study into the safety of Vioxx.

FDA investigators now estimate that over 27,000 excess cases of acute myocardial infarction and sudden cardiac death occurred in the USA between 1999 and 2003. In the November 5, 2004 editorial of The Lancet, Richard Horton states: “Today we publish results from a cumulative meta-analysis which show that the unacceptable cardiovascular risks of Vioxx (rofecoxib) were evident as early as 2000 – a full 4 years before the drug was finally withdrawn from the market by its manufacturer, Merck.”