A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a diverse class of drugs and are among the most commonly used analgesics for arthritic pain worldwide, though long-term use is associated with a spectrum of adverse effects. The introduction of cyclooxygenase-2-selective NSAIDs early in the last decade offered an alternative to traditional NSAIDs with similar efficacy and improved gastrointestinal tolerability; however, emerging concerns about cardiovascular safety resulted in the withdrawal of two agents (rofecoxib and valdecoxib) in the mid-2000s and, subsequently, in an overall reduction in NSAID use. It is now understood that all NSAIDs are associated with some varying degree of gastrointestinal and cardiovascular risk. Guidelines still recommend their use, but little is known of how patients use these agents. While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level.

Fig. 1

Proportion of global sales for NSAIDs [24]. Adapted by permission from IMS Health, copyright 2008

Fig. 2

Efficacy of NSAIDs compared with placebo for the treatment of OA of the knee [3]. Knee OA studies 2–13 weeks in length. Adapted by permission from BMJ Publishing Group Limited (Bjordal JM et al. BMJ; 329: 1317, copyright 2004)

Fig. 3

Risk of upper gastrointestinal bleeding/perforation with individual NSAIDs from published studies since 1990 [59]. ^aStudies published after 2000. P-values derived from heterogeneity test and n (number of studies). Adapted by permission from John Wiley & Sons, Inc (Massó González EL et al. Arthritis Rheum; 62: 1592, copyright 2010)

Fig. 4

Risk of vascular events with COX-2-selective agents versus nsNSAIDs [78]. Adapted by permission from BMJ Publishing Group Limited (Kearney PM et al. BMJ; 332: 1302, copyright 2006)