Comparative benefits of NSAIDs
Comparisons among the selective NSAID celecoxib, partially selective NSAIDs (etodolac, meloxicam), and nonselective NSAIDs revealed no differences in efficacy. ●●●
Comparisons among various nonselective NSAIDs exhibit no differences in efficacy for the relief of osteoarthritic symptoms. ●●●
For NSAIDs in general, higher doses increase efficacy for some measures of pain relief. ●●●
Topical diclofenac is similar to oral NSAIDs in efficacy for treating localized osteoarthritis. The risk of GI adverse events is lower with topical diclofenac than with oral NSAIDs, but dermatologic adverse effects (dry skin, rash, itching) are more likely with diclofenac. ●●○
GI adverse effects of NSAIDs
Higher doses of nonselective NSAIDs increase the risk of GI bleeding, but there is no clear association between duration of therapy and the risk of GI bleeding. ●●●
The risk of GI bleeding is higher in persons who had previous bleeding. ●●○
The risk of serious GI adverse effects is higher with naproxen than with ibuprofen. ●●●
The partially selective NSAIDs meloxicam and etodolac are associated with lower risk of ulcer-related complications and symptomatic ulcers than nonselective NSAIDs. ●●○
Concomitant use of nonselective NSAIDs and anticoagulants increases the risk of GI bleeding three- to sixfold over the risk with anticoagulants only. ●●○
Selective NSAIDs as a class are associated with a lower risk of ulcer complications than the nonselective NSAIDs naproxen, ibuprofen, and diclofenac. However, concomitant use of low-dose aspirin eliminates these GI benefits, resulting in risks similar to those of nonselective NSAIDs. ●●●
Concomitant use of low-dose aspirin and nonselective or selective NSAIDs increases the rate of endoscopically detected ulcers by about 6 percent. ●●●
Managing GI adverse effects of NSAIDs
Adding a histamine H2 antagonist, misoprostol, or PPI reduces the risk of endoscopically detected gastric and duodenal ulcers in patients prescribed a nonselective NSAID. ●●●
		•Indirect comparisons suggest that double-dose H2 antagonists could be more effective than standard dose.●●●
Adding a high-dose PPI lowers the risk of GI bleeding associated with celecoxib. ●●●
Adding a PPI could reduce the risk of GI adverse effects associated with the use of low-dose aspirin and celecoxib or nonselective NSAIDs. ●●●
In persons with average risk of GI bleeding:
		• Misoprostol reduces the risk of ulcer complications associated with nonselective NSAIDs. However, persons could adverse GI symptoms while taking misoprostol. ●●●
		• Adding a PPI reduces the risk of endoscopically detected ulcers and ulcer complications associated with ●●●
In persons with increased risk of GI bleeding who were prescribed a nonselective NSAID, PPIs:
		• Reduce the risk of endoscopically detected gastric or duodenal ulcers more than H2 antagonists.
		• Lower the risk of endoscopically detected duodenal ulcers more than misoprostol. Gastric ulcer risks were these agents. ●●●
Cardiovascular adverse effects of NSAIDs
All NSAIDs have deleterious effects on blood pressure, edema, and kidney function, but no consistent, clinically relevant differences have been found in risks of hypertension, heart failure, or impaired kidney function. ●●○
Celecoxib is associated with an increased risk of cardiovascular adverse effects compared with placebo. ●●○ Higher doses increase the risk, but there is no clear association between the duration of therapy and cardiovascular adverse effect risks. ●●●
Ibuprofen and diclofenac are associated with an increased risk of cardiovascular adverse effects and myocardial infarction, compared with placebo. Naproxen has not been associated with an increased risk of myocardial infarction. ●●○
Other findings on adverse effects of NSAIDs
Higher doses increase the risk of adverse effects in some cases. ●●●
The absolute risk of serious GI and cardiovascular complications increases with age. ●●○
Comparative benefits of NSAIDs and other agents
Acetaminophen:
	• Is modestly inferior to NSAIDs in reducing osteoarthritic pain. ●●●
	• Poses less risk of GI adverse effects than ●●●NSAIDs), but may cause elevations of liver enzymes at therapeutic doses in healthy (persons (●○○ to ●●○).
Glucosamine* and chondroitin:
	• No clear difference in effect on pain or function was found between oral NSAIDs (●●●) or chondroitin (and glucosamine ●○○).
	• A systematic review of higher quality, placebo controlled trials shows that glucosamine has some small benefits ●●●
Other analgesics
Salsalate and full-dose aspirin have similar efficacy. Comparisons to NSAIDs were unavailable in the included studies. ●●●
Topical capsaicin is effective for treating osteoarthritis compared with placebo, but is associated with increased local adverse effects. (Topical capsaicin has not been compared with NSAIDs.) ●○○
Topical salicylates are not effective for osteoarthritis in placebo comparisons, and are associated with increased local adverse effects. ●○○
Strength of evidence scale
High: ●●● There are consistent results from good-quality studies. Further research is very unlikely to change the conclusions.
Moderate: ●●○ Findings are supported, but further research could change the conclusions.
Low: ●○○ There are very few studies, or existing studies are flawed.
Insufficient: ○○○ Research is either unavailable or does not permit estimation of a treatment effect.