Merck & Co has published the results of a clinical trial indicating that its COX-2 inhibitor Arcoxia is as safe as the older non-steroidal anti-inflammatory drug diclofenac in terms of its cardiovascular risk profile, but was immediately criticised by cardiologist who said the choice of comparator drug was flawed.
The results of the MEDAL trial, reported at the American Heart Association annual meeting in Chicago and published simultaneously in The Lancet, found that Arcoxia (etoricoxib) had almost identical rates of clot-related cardiovascular events as diclofenac.
But critics of the study, including Steven Nissen of the Cleveland Clinic in Ohio, were quick to point out that diclofenac is widely-regarded as being particularly prone to thrombotic side effects, so its use as a comparator limits any safety conclusions that can be drawn for Arcoxia.
One key finding from the study, according to principal investigator Christopher Cannon of Brigham and Women’s Hospital in Boston, USA, was that increased potency of COX-2 inhibition does not necessarily equate to an increase in cardiovascular risk.
He also maintained that the choice of diclofenac was a fair one, given that it is the most widely-used NSAID in the world and only observational data suggests it has a higher cardiovascular risk profile than other drugs such as naproxen and ibuprofen.
Merck withdrew its marketing application for Arcoxia in the USA in 2002, at a time when concern over the tendency of COX-2 inhibitors to cause heart attacks and strokes, which led to the withdrawal of Vioxx (rofecoxib) from the market in 2004, was starting to build.
The company re-filed the application in 2003, and is in the process of supplying additional information to the US Food and Drug Administration (FDA) under the terms of the current ‘approvable’ status for the product. The application is only for Arcoxia’s use as a treatment for osteoarthritis, and is due to be decided on by the FDA next April.
Arcoxia had been billed as a more potent alternative to Vioxx that would help Merck in its jostle for market share with arch-rival Pfizer, which sells its own COX-2 inhibitor Celebrex (celecoxib). But despite the fact that it is already on the market in some 62 countries around the world, the concern over its safety has limited sales.