The widespread use of NSAIDs means that there is considerable interest in the regulation of this therapeutic class. Additionally, following the voluntary discontinuation of Vioxx (rofecoxib) in 2004, regulators became concerned about potential adverse cardiovascular outcomes.

FDA advisory committee meetings in 2005 and 2014 concluded that NSAIDs increase the risk of myocardial infarction (MI) in high-risk populations, and they supported the need for additional label warnings and studies to further clarify the increased risk. Whether the risk is really a disease-like effect or the result of cyclooxygenase (COX)-2 selectivity. The 2005 meeting changed the labeling of all NSAIDs, including over-the-counter NSAIDs, to emphasize this risk what is naproxen

The 2014 FDA Advisory Committee Meeting on NSAID Cardiovascular Risk included FDA's review of data available after 2005, emphasizing that naproxen's potential cardiovascular risk is lower than that of other NSAIDs, and a review of PRECISION Discussion of Progress (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen), an ongoing cardiovascular safety study [9]. The committee reiterated its position that class labeling is appropriate and should not differentiate between products, forms, and dosages (including over-the-counter medicines). Still, many committee members said the data suggested that naproxen had a more favorable cardiovascular risk profile than other NSAIDs, even though it did not meet the evidence criteria to support a regulatory label change. In addition, the risk can be reduced with lower doses or shorter periods of use, such as over-the-counter naproxen. Additionally, many other regulatory agencies have contributed to the safety of NSAIDs, but country-by-country recommendations vary by ingredient. For example, in the United Kingdom, where diclofenac was reverted from over-the-counter to prescription status due to safety concerns, the European Medicines Agency (EMA) determined that naproxen "may be associated with a lower risk of arterial thrombotic events than COX-2 inhibitors and other NSAIDs." inflammatory drugs, but small risks cannot be ruled out” [10].

We reviewed the body of evidence on naproxen and cardiovascular safety in the context of NSAIDs as a class.