22 December 2004. With safety concerns about rofecoxib (Vioxx®), celecoxib (Celebrex®), and now naproxen, it seems that nonsteroidal antiinflammatories (NSAIDs) are dropping like flies. On Monday last, the National Institute on Aging halted the Alzheimer’s Disease Antiinflammatory Prevention Trial (ADAPT), in part because “Preliminary information from the study showed some evidence of increased risk of cardiovascular events, when compared to placebo, to patients taking naproxen,” according to a statement released Monday by the FDA.
ADAPT began enrolling patients in early 2001 (see ARF related news story) based on evidence that certain NSAIDs may offer some protection against Alzheimer disease (AD). The trial was designed to evaluate the protective effects of two drugs, celecoxib and naproxen. When Merck recently withdrew Vioxx from the market because of safety concerns (see ARF related news story), the action sent ripples through the drug and healthcare industries and made many take a second look at celecoxib, a drug in the same class—designed to block the enzyme cyclooxygenase-2 (COX-2). Four days ago, Pfizer reported similar long-term safety issues with celecoxib—increased risk of cardiovascular disease—following evaluation of data from a clinical trial designed to test the drug’s ability to prevent adenomas (see Pfizer statement). Celebrex has not been withdrawn, but patients and doctors have been encouraged to consider alternative therapies (see FDA statement).
Last Friday's news from Pfizer may eventually have put an end to ADAPT, despite the fact that celecoxib doses (up to 200 mg) given to ADAPT patients are fourfold lower than those found to confer increased risk of cardiovascular disease (800 mg/day), and the fact that in another long-term trial, patients taking 400 mg/day of the drug had no evidence of adverse cardiovascular events. But the latest news, from ADAPT itself, that naproxen also confers risk for cardiovascular events signaled the end of the trial.
The results come as a surprise to many, especially since naproxen (better known to many as Aleve®) has been approved since the mid-1970s and is available over the counter. In addition, because it is not a selective COX-2 inhibitor, there was reason to doubt that it would be tainted with the same brush as the selective inhibitors.—Tom Fagan.