The Agency for Healthcare Research and Quality (AHQR) released a recent report that reviewed all of the studies published on analgesics (pain relievers) for osteoarthritis. Here are excerpts from their report. It’s written for prescribers, but I think many in the lay audience will benefit from it.
Clinical Bottom Line:
NSAIDs versus NSAIDs
1. No difference in efficacy in relieving osteoarthritic pain was found between celecoxib, the partially selective NSAIDs meloxicam and etodolac, and nonselective NSAIDs.
2. No difference in efficacy was found among various nonselective NSAIDs for the relief of osteoarthritic symptoms.
NSAIDs versus other agents
- Acetaminophen was modestly inferior to NSAIDs in reducing osteoarthritic pain but was associated with less risk of GI adverse effects than were NSAIDs.
- No clear difference was found between glucosamine* and oral NSAIDs for pain or function. Evidence from a systematic review of higher quality trials suggests that glucosamine had some small benefits for pain over placebo.
- No clear difference was found between chondroitin and oral NSAIDs for pain or function.
*Note: Most trials showing therapeutic benefits from glucosamine were conducted with pharmaceutical-grade glucosamine not available in the United States. Therefore, the findings of these trials may not be applicable to currently available over-the-counter preparations.
Comparative Adverse Effects of Oral Agents
- Acetaminophen could cause elevations of liver enzymes at therapeutic doses in healthy people.
- Selective NSAIDs as a class were associated with less risk of ulcer complications than were the nonselective NSAIDs naproxen, ibuprofen, and diclofenac.
- The partially selective NSAIDs meloxicam and etodolac were associated with less risk of ulcer-related complications and symptomatic ulcers than were various nonselective NSAIDs.
- A higher risk of serious GI adverse effects was found with naproxen than with ibuprofen.
- Celecoxib and the nonselective NSAIDs ibuprofen and diclofenac were associated with an increased risk of CV adverse effects when compared with placebo.
- The nonselective NSAIDs ibuprofen and diclofenac, but not naproxen, were associated with an increased risk of heart attack when compared with placebo.
- All NSAIDs had deleterious effects on blood pressure, edema, and kidney function. There were no consistent clinically relevant differences between celecoxib, partially selective NSAIDs, and nonselective NSAIDs in the risk of hypertension, heart failure, or impaired kidney function.
Comparing Dosage and Duration of Treatment
- Higher doses of NSAIDs were associated with greater efficacy for some measures of pain relief but also with more adverse effects in some cases.
- Higher doses of celecoxib increased the risk of CV adverse effects; however, there was no clear association between the duration of therapy and the risk of CV adverse effects.
- Higher doses of nonselective NSAIDs increased the risk of GI bleeding; however, there was no clear association between the duration of therapy and the risk of GI bleeding.
Factors Affecting Outcomes Concomitant Medication Use
- Concomitant use of low-dose aspirin with celecoxib or a nonselective NSAID increased the rate of endoscopic ulcers by about 6 percent.
- Concomitant use of low-dose aspirin eliminated the GI benefits of selective NSAIDs, resulting in risks similar to those for nonselective NSAIDs. However, adding a PPI could reduce the risk of GI adverse effects associated with the use of either celecoxib or nonselective NSAIDs plus low-dose aspirin.
- Concomitant use of anticoagulants and nonselective NSAIDs increased the risk of GI bleeding three-fold to six-fold when compared with anticoagulant use without NSAIDs.
Adding an H-2 Antagonist, Misoprostol, or a PPI on GI Adverse Effects Associated With NSAIDs
- Adding an H-2 antagonist, misoprostol, or a PPI reduced the risk of endoscopically detected gastric and duodenal ulcers in patients prescribed a nonselective NSAID.
- Misoprostol was the only gastroprotective agent to reduce the risk of ulcer-related complications versus placebo in individuals with average risk of GI bleeding who were prescribed nonselective NSAIDs. However, individuals could experience other adverse GI symptoms while taking misoprostol.
- In individuals with increased risk of GI bleeding who were prescribed a nonselective NSAID, adding a PPI resulted in a reduced risk of endoscopically detected duodenal ulcers when compared with misoprostol or H-2 antagonists, a lower risk of endoscopically detected gastric ulcers when compared with H-2 antagonists, and a similar risk of endoscopically detected gastric ulcers when compared with misoprostol.
- Celecoxib plus a PPI could reduce the risk of endoscopic ulcers and ulcer-related complications when compared to celecoxib alone in individuals at average risk. Celecoxib plus a high-dose PPI lowered the risk of GI bleeding when compared to celecoxib alone.
- When compared with placebo, double-dose H-2 antagonists could be more effective than standard-dose H-2 antagonists for reducing endoscopically detected gastric and duodenal ulcers.
- Topical diclofenac was similar in efficacy to oral NSAIDs for treating localized osteoarthritis.
- Topical NSAIDs were associated with a lower risk of GI adverse effects but a higher risk of dermatologic adverse effects (dry skin, rash, and itching) when compared to oral NSAIDs.
- Topical salicylates were not effective for patients with osteoarthritis and were associated with increased risk of local adverse effects. Topical salicylates were not compared to NSAIDs
- Topical capsaicin was effective for treating osteoarthritis but was associated with an increase in local adverse effects. Topical capsaicin was not compared to NSAIDs.
COX = cyclooxygenase; CV = cardiovascular; GI = gastrointestinal; H-2 antagonist = histamine-2 receptor antagonist; NSAID = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor.
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