Risks versus Benefits of COX-2-selective NSAIDs
Purpose: A summary of the basic science underlying the current controversies regarding cyclooxygenase-2 (COX-2)-selective nonsteroidal antiinflammatory drugs (NSAIDs), including data on their cardiovascular safety, their gastrointestinal (GI) benefits, cost-effectiveness, physician-prescribing trends, and recommendations for prescribing these agents is presented.
Summary: A number of randomized controlled trials (RCTs) have reported that COX-2-selective NSAIDs increase cardiovascular events, although there appear to be gradations of risks among the COX-2-selective NSAIDs. In addition, traditional NSAIDs may increase the risk for cardiovascular events, complicating the interpretation of RCTs that use traditional NSAIDs as comparators. Selective inhibitors of COX-2-selective NSAIDs are effective antiinflammatory and analgesic drugs with improved upper-GI safety compared to traditional NSAIDs. Data on the cost-effectiveness of COX-2-selective NSAIDs indicate that they should be limited to patients at high risk for upper-GI adverse effects. However, they had been increasingly used in patients with lower GI risks until recent events reversed that trend. Circumstances under which COX-2-selective NSAIDs may be appropriate are in patients at high GI risk and in patients who did not respond to multiple traditional NSAIDs. The national spotlight in the United States on NSAID-related adverse events and recent lawsuits against health care providers prescribing COX-2-selective NSAIDs further highlights the need for provider-patient communication and risk disclosure. The relative cardiovascular risks of NSAIDs are similar in magnitude to other currently prescribed therapies.
Conclusion: Health care providers must consider the efficacy, GI and cardiovascular risks, concomitant medications, and costs when determining the appropriateness of COX-2-selective NSAID therapy.

Cyclooxygenase-2 (COX-2)-selective nonsteroidal antiinflammatory drugs (NSAIDs) have often been used in recent years due to their apparent gastrointestinal (GI) safety advantage over traditional or nonselective NSAIDs (hereafter referred to as traditional NSAIDs). In the United States, there were three COX-2-selective NSAIDs available (celecoxib, rofecoxib, valdecoxib). The labeling for celecoxib, rofecoxib, and valdecoxib was approved by the Food and Drug Administration (FDA) in December 1998, May 1999, and November 2001, respectively. Celecoxib is the only agent in this class currently available in the United States. In Europe, three additional agents are available: lumiracoxib, etoricoxib, and parecoxib, the parenteral form of valdecoxib.

Although traditional and COX-2-selective NSAIDs have commonly been used for their antiinflammatory and analgesic effects in many diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA), concerns regarding the safety of these drugs have been raised, particularly for increased risk of arterial thrombotic events (i.e., myocardial infarction, unstable angina, cardiac thrombus, resuscitated cardiac arrest, sudden or unexplained death, ischemic stroke, and transient ischemic attacks). In light of the overwhelming and sometimes contradictory information for patients and physicians regarding the apparent safety of NSAIDs, this article will summarize the basic science underlying the current controversies for the cardiovascular safety data, the GI protective benefits of COX-2-selective NSAIDs, cost-effectiveness, trends in physician prescribing of NSAIDs in response to recently released cardiovascular safety data, and, finally, contemporary recommendations for prescribing of COX-2-selective NSAIDs.