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Analgesics for Osteoarthritis—An Update

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Knowledge Gaps and Future Research Needs (2 of 3)

Meta-analyses of the risks associated with selective COX-2 inhibitors need to better assess the effects of dose and duration, as most of the CV adverse effects have only occurred with prolonged use and at higher doses.

The CV safety of nonselective NSAIDs has not been adequately assessed in large, long-term clinical trials. Naproxen in particular might have a different CV safety profile than other NSAIDs and should be investigated in long-term, appropriately powered trials.

Large, long-term trials of the GI and CV safety associated with full-dose aspirin, salsalate, or acetaminophen in comparison to nonaspirin NSAIDs or placebo are lacking.

The effects of alternative dosing strategies, such as intermittent dosing or drug holidays, have not been well studied. Studies evaluating the benefits and risks associated with such strategies when compared with conventional dosing could help clarify the effects of these alternative dosing strategies. In addition, although there is speculation that once-daily versus twice-daily dosing of certain COX-2 inhibitors could affect CV risk; this hypothesis has not yet been tested in a clinical trial.