The Food and Drug Administration says that the nonsteroidal anti-inflammatory drug naproxen may carry a lower risk of cardiovascular thromboembolic events than that of other selective or nonselective NSAIDs.
The agency presented evidence for that finding in briefing documents that were issued ahead of a Feb. 10-11 joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee.
At that meeting, the FDA will ask the two advisory committees if the data show that naproxen may have a lower risk for CV thrombotic events. The agency also will ask whether warnings or restrictions should be considered for patients who might be at higher risk for CV events, and whether over-the-counter NSAIDs are acceptable at the currently available doses.
According to the documents, the primary evidence for a better cardiovascular safety profile for naproxen comes from a meta-analysis conducted by the Coxib and traditional NSAID Trialists’ (CNT) Collaboration at Oxford University. The principal investigators gave the FDA a prepublication copy of the study in February 2013. The meta-analysis, which assessed both the gastrointestinal and the cardiovascular risks of nonselective NSAIDs, concluded that naproxen had a lower risk of CV thromboembolic events than did celecoxib and ibuprofen (Lancet 2013;382:769-79).
The FDA has been assessing the safety profile of both cyclooxygenase-2 (COX-2) selective NSAIDs and nonselective NSAIDs for almost a decade. In 2005, the arthritis and drug safety committees pondered the safety of rofecoxib and celecoxib. Based on the panels’ conclusions, the FDA concluded that the risk for CV thromboembolic events was present for both COX-2 selective NSAIDs and nonselective NSAIDs.
The agency subsequently asked Pfizer to voluntarily withdraw valdecoxib (Bextra) from the U.S. market, and all prescription NSAIDs were given a boxed warning on the potential for serious adverse CV events. (Merck had previously withdrawn rofecoxib voluntarily from the U.S. market in 2004.) NSAIDs also carry a warning on the potential for gastrointestinal events. A Medication Guide was developed for patients to inform them of the risk of CV events and gastrointestinal bleeding with all NSAIDs. And companies that made nonselective NSAIDs were asked to conduct comprehensive reviews of their existing controlled clinical trial databases to evaluate CV safety.
The Oxford meta-analysis reinforces the agency’s conclusions from 2005, according to the briefing documents. It also brings into question whether Pfizer should continue its long-term study, Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen (PRECISION), which was begun in the wake of the 2005 panel meeting at the agency’s behest.
The necessity – and wisdom – of continuing that trial is one of the issues that will be discussed at the Feb. 10-11 joint advisory committee meeting.
On Twitter @aliciaault