A class of painkillers known as nonsteroidal anti-inflammatory drugs (NSAIDs) are popular painkillers. A downside of these medications is that they pose a risk for cardiovascular events such as heart attacks and stroke. On January 28, the Food and Drug Administration announced that Aleve (naproxen), manufactured by Bayer AG, appears to have less risk of a cardiovascular event than other NSAIDs (e.g., ibuprofen (Motrin and Advil) and celecoxib (Celebrex), which is a prescription medication manufactured by Pfizer Inc.
The FDA cites evidence from a number of clinical studies that the agency has evaluated since 2005, when the cardiovascular risks of NSAIDs became an issue of widespread public concern. At the time, the FDA assessed the evidence and concluded that the data “did not permit rank ordering of the drugs with regard to cardiovascular risk.” However, the latest analysis may modify that opinion. The FDA plans to convene an advisory committee of independent cardiologists and other physicians to advise whether to distinguish among the drugs in labeling. Obviously, the findings of the advisory committee could provide an advantage to Bayer.
The FDA notes that current evidence “raises the possibility that, in contrast to the 2005 conclusions, there may be a lower risk for one NSAID, naproxen.” After holding a hearing in 2005, the agency required makers of prescription-strength NSAIDs to convey its strictest boxed warning regarding the increased risks of heart attacks and strokes in addition to potentially life-threatening stomach bleeding. Makers of over-the-counter such as Advil, Motrin, Aleve and generic versions of the products were required to add additional information regarding bleeding risks and more detailed instructions about how to use the medications. At that time, the FDA noted that there did not appear to be an increased risk of heart attacks and strokes with the over-the-counter painkillers, which usually contain lower doses than prescription-strength medications. The FDA stated that short-term use of the drugs to control acute pain appeared to be comparatively safe.
The most recent study evaluated certain particularly vulnerable patients, including a Danish registry of patients hospitalized for heart failure. In the Danish study of NSAIDs, naproxen was not related to an apparent increase in risk of death; however the other NSAIDs were, except for low doses of ibuprofen. The new study reported: “Risks in absolute terms are considerably higher for vulnerable patients, but NSAID use has also been shown to increase cardiovascular events among apparently healthy patients.”
The FDA has also requested Pfizer to conduct a safety study that would evaluate potential cardiovascular risks with Celebrex compared to naproxen and ibuprofen. The study is currently ongoing; however, in the January 28 announcement, the FDA has recommended halting the study because naproxen has since been shown to be safer.
In a document prepared for the FDA’s upcoming advisory committee meeting, Bayer noted, the “body of evidence supports the [cardiovascular] safety of naproxen at both over-the-counter and prescription doses.” Materials that Pfizer presented to the FDA advisory committee noted that the evidence that has emerged since 2005 “has not provided a definitive answer to remaining issues on cardiovascular safety of this class of drugs” and that existing labeling for the drugs is appropriate. In a January 28 statement, Pfizer noted that the risk profiles of its pain killer medication “remain positive” and that “current class labeling for prescription and over-the-counter NSAIDs is appropriate.” It added that “current evidence does not support changes or differential labeling within the class.”