Risks versus benefits of cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs

Abstract

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

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

“…Taking into account the high cost of COX-2 selective inhibitors (17,18), such as valdecoxib, in comparison with the conventional NSAIDS like piroxicam, our data support the suggestion that there are no sufficient clinical advantages for the prescription of valdecoxib after lower third molar removal.…”

“…It is worth mentioning that recent reports have suggested an increased risk of cardiovascular events for patients taking coxibs. Therefore, clinicians must consider the efficacy, gastrointestinal and cardiovascular risks, concomitant medications and costs when determining the appropriateness of COX-2 selective NSAID therapy (14)(15)(16)(17)(18)(19).…”

“…In contrast, there are only seven reports in the dental literature concerning the clinical use of valdecoxib, a COX-2 selective inhibitor, for postoperative pain control in patients who undergo dental surgeries (13,(25)(26)(27)(28)(29)(30). In these studies, either different doses of valdecoxib or its injectable prodrug parecoxib were tested (9,16,17,19) or a comparison with rofecoxib, another COX-2 selective inhibitor, was performed (25,28,30). Additionally, only one study compared valdecoxib with a traditional non-selective NSAID (ketorolac), with both agents being parenterally administered (29).…”

Organ and prenatal toxicity of nonsteroidal anti-inflammatory drugs

“…As expected, both selective and non-selective COX inhibitors can impair renal flow and glomerular filtration, as well as sodium and potassium excretion, which leads to swelling, pressure increase and hyperkalemia. This was confirmed by numerous studies [16,18]. Moreover, it was demonstrated that selective COX-2 inhibitors inhibit renin secretion in the macula densa, stimulated by a decrease in sodium concentration.…”

“…This situation comes about depending on the inhibition of platelet activity by COX-1. Selective COX-2 inhibitors do not display antithrombotic action, but can intensify blood coagulation by inhibiting the synthesis of prostacyclins in the endothelium [18,27]. This, however, was not explicitly confirmed in clinical trials [23].…”