Coxibs versus combination NSAID and PPI therapy for chronic pain: an exploration of the risks, benefits, and costs.

Objective: To systematically review studies qualitatively to compare the risks (gastrointestinal [GI] and cardiovascular) and benefits (pain control) of cyclooxygenase-2 inhibitors (coxibs) relative to an alternative therapy of a nonselective nonsteroidal antiinflammatory drug (NSAID) combined with a proton-pump inhibitor (PPI) and explore circumstances when coxibs may be appropriate.

Methods: Relevant studies were identified through a search of MEDLINE (Ovid Technologies, 1985-November 2005; English language, clinical trial), PubMed (1985-November 2005; English language, clinical trial, humans), and the Cochrane Collaboration using the terms selective COX-2 inhibitors and coxibs, as well as the various chemical names for specific coxib agents. Studies that compared a coxib with a nonselective NSAID and provided data concerning our outcomes of interest were included and categorized by the outcome variable, as well as by the specific coxib studied.

Results: The majority of the numerous studies that evaluated pain as an endpoint showed no difference between coxib and nonselective NSAID therapy. However, while limited, preliminary safety data regarding the effects of both classes on the upper and lower GI tract suggest coxib superiority. Although coxibs are associated with an increased risk of cardiovascular adverse events (CVEs) compared with placebo, this effect has not been conclusively shown compared with nonselective NSAIDs. Currently, coxib therapy is more expensive than combination therapy using a nonselective NSAID plus a PPI.

Conclusions: Compared with combination therapy including a nonselective NSAID and PPI, coxibs provide equivalent pain control and may have a lower GI tract complication profile, but at an unknown increased risk of CVEs and a greater financial cost. Coxib therapy may be an appropriate treatment for chronic pain in select patients with higher risks of GI complications, lower risk of CVEs, and in whom greater cost is not a restraint.