Advisors Call for No New Heart Warnings for NSAIDs

Abstract

SILVER SPRING, MD – No major change is needed to the warning labels on prescription and over-the-counter nonsteroidal anti-inflammatory medications, according to two panels of Food and Drug Administration advisers. The members of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee said that the evidence about potentially new cardiovascular (CV) risks, which may target arthritis patients with drugs in the class, was not sufficient to change labeling. And they said there were not enough data to suggest that naproxen presented a substantially lower risk of CV events than did either ibuprofen or selective NSAIDs, such as cyclooxygenase-2 inhibitors. But some panelists said that even without a label change, the evidence on naproxen – which showed a trend toward a better safety profile – would probably sway them to prescribe or recommend it more often, especially in patients at risk for CV side effects. However, there was concern for patients with rheumatic diseases, who are considered to be at higher risk for CV events. Robert Lahita, MD, PhD, an arthritis committee member and a professor of medicine at Rutgers Biomedical and Health Sciences, Newark, NJ, said that his rheumatoid patients “take NSAIDs like candy.” Irwin J. Russell, MD, PhD, a fibromyalgia researcher at the Arthritis and Osteoporosis Center of South Texas, San Antonio, said that the data on NSAIDs should prompt inquiries into whether the elevated cardiovascular disease risk in rheumatic patients might be linked to their chronic use of the medications. In June 2005, the FDA required all prescription NSAIDs to have a boxed warning on the potential for serious adverse CV events. NSAIDs also carry a warning on the potential for gastrointestinal adverse events. A Medication Guide was developed for patients to inform them of the risk of CV events and gastrointestinal bleeding with all NSAIDs. PA/LTC PerspectiveUniversity of Maryland School of Nursing Professor Barbara Resnick, PhD, CRNP, FAAN, FAANP, said that several issues regarding NSAIDs raise concerns in the PA/LTC population.“For some individuals, NSAIDs provide extraordinary pain relief and truly optimize quality of life. For others, these medications make little difference, and the pain they experience may be better managed by behavioral interventions and other treatment options. Thus, use of NSAIDs, including naproxen, should be individualized and considered as a short-term option for pain relief.” University of Maryland School of Nursing Professor Barbara Resnick, PhD, CRNP, FAAN, FAANP, said that several issues regarding NSAIDs raise concerns in the PA/LTC population. “For some individuals, NSAIDs provide extraordinary pain relief and truly optimize quality of life. For others, these medications make little difference, and the pain they experience may be better managed by behavioral interventions and other treatment options. Thus, use of NSAIDs, including naproxen, should be individualized and considered as a short-term option for pain relief.” The latest panel meeting was held because “9 years later, there are more data available and questions still remain,” said John Jenkins, MD, director of the FDA's Center for Drug Evaluation and Research. The committee did say that it would like to see clearer warnings on over-the-counter NSAIDs, especially emphasizing that patients should take the lowest possible dose for the shortest period of time. In briefing documents that were issued ahead of the joint meeting, the FDA said that naproxen may carry a lower risk of CV thromboembolic events than that of other selective or nonselective NSAIDs. According to the documents, the primary evidence for a better CV safety profile for naproxen comes from a meta-analysis conducted by the Coxib and traditional NSAID Trialists’ (CNT) Collaboration at Oxford University (Lancet 2013;382[9894]:769–79). The Oxford meta-analysis brings into question whether Pfizer should continue its long-term study comparing the safety of naproxen, ibuprofen, and celecoxib, which was begun in the wake of the 2005 events and at the agency's behest.