CURRENT OPINION Coxibs Refocus Attention on the Cardiovascular Risks of Non-Aspirin NSAIDs Dixon Thomas 1 • Zoya Ali 1 • Seeba Zachariah 1 • Kishore Gnana Sam Sundararaj 1 • Matthew Van Cuyk 2 • Jason C. Cooper 2 Ó Springer International Publishing Switzerland 2017 Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) were differentiated from steroidal anti-inflam- matory medicines to help clinicians who needed to use anti-inflammatory agents that were safer than steroids. With market entry of rofecoxib in 1999, NSAIDs were then further classified into traditional NSAIDs and cyclooxy- genase (COX)-2 inhibitors (coxibs), the latter posing potentially fewer gastrointestinal risks. In 2005, rofecoxib was withdrawn from the market because of concerns about the risk of heart attack and stroke with long-term use, and clinical practice began focusing more on the cardiovascular versus gastrointestinal safety of coxibs. Since then, many coxibs have remained unapproved by the US FDA or have been removed from the market. This article explains how coxibs refocused attention on the cardiovascular safety of NSAIDs and the general implications of that. COX-2 activity/specificity is one factor associated with increased cardiovascular risks; however, these risks cannot be attributed to coxibs alone. The traditional NSAIDs (i.e., meloxicam, etodolac, and nabumetone) have significant COX-2 specificity, but naproxen and ibuprofen have less specificity. All NSAIDs, whether traditional or a coxib, pose some cardiovascular risks. It is possible that clinicians continue to focus more on decreasing the immediate gastric risks than preventing the later cardiovascular risks. The cardiovascular risks posed by NSAIDs should not be dis- regarded for the sake of achieving gastrointestinal benefits. Current recommendations suggest NSAIDs should be considered a single class of non-aspirin NSAIDs. Preferred NSAIDs are ibuprofen and naproxen. Coxibs are preferred in patients with low cardiovascular risk and high gas- trointestinal risk who are intolerant to anti-dyspepsia therapy. Key Points Non-steroidal anti-inflammatory drugs (NSAIDs) are now considered as one class: non-aspirin NSAIDs. Cardiovascular safety should not be disregarded for the sake of achieving gastrointestinal benefits; NSAIDs of preference are ibuprofen and naproxen. Coxibs should be used in patients who are at risk of gastrointestinal side effects and intolerant to anti- dyspepsia therapy. 1 Introduction The classification of non-steroidal anti-inflammatory drugs (NSAIDs) has been difficult. When cyclooxygenase (COX)-2 inhibitors (coxibs) entered the market, NSAIDs were separated into coxibs and traditional NSAIDs. The key marketing promotions for coxibs focused on the ben- efits of reduced gastrointestinal adverse effects compared with those associated with traditional NSAIDs [1]. How- ever, when the cardiovascular risks posed by coxibs were discovered, coxibs were no longer considered safer than traditional NSAIDs [2]. Like in any other pharmacological & Dixon Thomas dixon.thomas@gmail.com 1 College of Pharmacy, Gulf Medical University, Post Box: 4184, Ajman, United Arab Emirates 2 Medical University of South Carolina Drug Information Center, Charleston, SC, USA Am J Cardiovasc Drugs DOI 10.1007/s40256-017-0223-6