COX-2 inhibition: what we learned--a controversial update on safety data.

IMPORTANCE: Cyclooxygenase type 2 (COX-2)-selective nonsteroidal anti-inflammatory drugs (NSAIDs) (c2sNSAIDs) have been scrutinized relative to the less costly nonselective NSAIDs (nsNSAIDs). The conclusions reached were not always consistent with the data, and best treatment choices for patients were not always recommended.
OBJECTIVE: The data that were used to criticize the c2sNSAIDs are reexamined in a controversial light, demonstrating that the presence of reverse bias was often, but not always, present. EVIDENCE REVIEW: A review of both Pubmed and news media articles relating to nsNSAIDs and c2sNSAIDs was conducted. References were selected on the basis of relevance to the controversies.
FINDINGS: The initial claims for the c2sNSAIDs of reduced gastrointestinal (GI) injury and preservation of platelet function were soon dwarfed by concerns regarding increased cardiovascular (CV) risk with publication of the Vioxx Gastrointestinal Outcomes Research trial for rofecoxib. Initial prothrombotic theories had a poor basis for explaining these concerns and have since largely been replaced with more credible explanations, including blood pressure elevations known to occur with all NSAIDs. Between data suggesting increased CV risk and under political pressure and public outcry, rofecoxib was withdrawn from the market in 2004. Soon, all c2sNSAIDs were under scrutiny. The Food and Drug Administration has since grouped all NSAIDs, whether c2sNSAID or nsNSAID, into one class with similar warnings regarding skin, CV, renal, and GI side effects. CONCLUSIONS AND RELEVANCE: The entire "COX-2 debacle" is reminiscent of past events with NSAIDs. Amid this public, media, and political hysteria, it is not clear if we will see any more NSAIDs (selective or otherwise) approved in the near future. Wiley Periodicals, Inc.