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Published online: 8 November 2016
© The Author(s) 2016. This article is published with open access at Springerlink.com
Abstract The voluntary withdrawal of Vioxx (rofecoxib) from the market in 2004, as well as the 2005 and 2014 US FDA Advisory Committee meetings about non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, have raised questions surrounding the use of NSAIDs in atrisk populations. This paper discusses the cardiovascular safety profile of naproxen in the context of the NSAID class. The balance of evidence suggests that cardiovascular risk correlates with cyclooxygenase (COX)-2 selectivity, and the low COX-2 selectivity of naproxen results in a lower cardiovascular risk than that of other NSAIDs. The over-the-counter (OTC) use of naproxen is expected to pose minimal cardiovascular risk; however, the benefitrisk ratio and appropriate use should be considered at an individual patient level, particularly to assess underlying conditions that may increase the risk of events. Likewise, regulatory authorities should revisit label information periodically to ensure labeling reflects the current understanding of benefits and risks.
1Introduction
1.1 Non-Steroidal Anti-Inflammatory Drug (NSAID) Background
1.1.1 Therapeutic Importance
Musculoskeletal aches and pains are one of the most common medical complaints around the world, and increasing life expectancies are driving an increased incidence of degenerative joint disease, burdening patients and healthcare systems [1]. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used class of analgesic drugs, with approximately 30 million users worldwide daily [2] and over 100 million prescriptions every year in the USA [3]. NSAIDs continue to be one of the most effective and widely used forms of non-surgical pain relief for osteoarthritis [1]. A significant portion of the population appropriately manages pain with over-thecounter (OTC) NSAIDs [4]. In contrast, other prescription pain relievers (e.g., opioids) lend themselves to abuse, which has become a growing epidemic [5].
1.1.2 Regulatory Interest
The widespread use of NSAIDs means there is significant regulatory interest in this therapeutic category. Furthermore, after the voluntary withdrawal of Vioxx (rofecoxib) in 2004, regulatory authorities have focused on potential adverse cardiovascular outcomes.
The US FDA Advisory Committee meetings in both 2005 and 2014 concluded that NSAIDs increased the risk of myocardial infarction (MI) in high-risk individuals, and they supported the need for additional label warnings and studies to further clarify whether the increased...