Are there any important differences between available nonsteroidal anti-inflammatory drugs (NSAIDs)?

TRADE-OFF BETWEEN BENEFITS AND HARMS

Choice Between Different NSAIDs. Systematic reviews showed no important differences in effectiveness between different NSAIDs for the symptoms of musculoskeletal disorders. Systematic reviews showed that cyclooxygenase-2 (COX-2) inhibitors reduced symptomatic ulcers compared with older NSAIDs. However, the COX-2 inhibitor rofecoxib was withdrawn from the market in 2004 after it was found to increase the risk of myocardial infarction, and there is good evidence that other COX-2 inhibitors also may increase cardiovascular risk.

UNLIKELY TO BE BENEFICIAL

NSAIDs in Increased Doses. Systematic reviews showed that the benefits of NSAIDs increased towards a maximum value at high doses. Recommended doses are close to creating the maximum benefit. In contrast, three systematic reviews showed no ceiling for adverse effects, which increased in an approximately linear fashion with dose.

What are the effects of cotreatments on reducing the risk of the adverse gastrointestinal effects of NSAIDs?

TRADE-OFF BETWEEN BENEFITS AND HARMS

Misoprostol in Persons Who Cannot Avoid NSAIDs. One systematic review showed that misoprostol reduced serious gastrointestinal complications and symptomatic ulcers compared with placebo. The review did not assess adverse effects of misoprostol. However, another systematic review showed that misoprostol increased withdrawals caused by adverse events, mainly diarrhea and abdominal pain, compared with placebo. Randomized controlled trials (RCTs) provided insufficient evidence to compare the effects of misoprostol with proton pump inhibitors (PPIs) or histamine H₂ blockers.

UNKNOWN EFFECTIVENESS

H2Blockers in Persons Who Cannot Avoid NSAIDs. One systematic review provided insufficient evidence about the effects of H₂ blockers on serious gastrointestinal complications and symptomatic ulcers. It showed that H₂ blockers reduced endoscopically diagnosed ulcers compared with placebo, but the clinical relevance of this finding is uncertain. RCTs provided insufficient evidence to compare the effects of H₂ blockers with misoprostol or PPIs.

PPIs in Persons Who Cannot Avoid NSAIDs. One systematic review provided insufficient evidence regarding the effects of PPIs compared with placebo on serious gastrointestinal complications and symptomatic ulcers. Another systematic review showed that PPIs reduced endoscopically diagnosed ulcers compared with placebo, but the clinical relevance of this finding is uncertain. RCTs provided insufficient evidence to compare the effects of PPIs with Misoprostol or H₂ blockers.

What are the effects of topical NSAIDs?

LIKELY TO BE BENEFICIAL

Topical NSAIDs (For Up to Two Weeks). One systematic review that included persons with acute musculoskeletal pain conditions showed limited evidence that topical NSAIDs reduced pain compared with placebo at one week. One systematic review that included persons with osteoarthritis showed limited evidence that topical NSAIDs reduced pain compared with placebo at two weeks but showed no significant difference between treatments at four weeks.

UNKNOWN EFFECTIVENESS

Topical NSAIDs (For Longer than Two Weeks). One systematic review that included persons with osteoarthritis showed no significant difference between topical NSAIDs and placebo at four weeks. The review showed no evidence regarding the effects of topical NSAIDs compared with placebo for longer than four weeks.

Topical vs. Systemic NSAIDs or Alternative Analgesics. Two systematic reviews showed insufficient evidence to compare topical with oral NSAIDs for pain in acute musculoskeletal pain conditions or osteoarthritis. We found no systematic review or RCT comparing topical NSAIDs with paracetamol for musculoskeletal conditions.

Definition

NSAIDs have anti-inflammatory, analgesic, and antipyretic effects, and they inhibit platelet aggregation. This chapter focuses on the use of NSAIDs for the treatment of the symptoms of musculoskeletal conditions. NSAIDs have no documented effect on the course of musculoskeletal diseases such as osteoarthritis. NSAIDs inhibit the enzyme COX, which has two known isoforms, COX-1 and COX-2. NSAIDs often are categorized according to their ability to inhibit the individual isoforms; newer NSAIDs predominantly inhibit the COX-2 isoform, and older NSAIDs often are less specific inhibitors.

Incidence

NSAIDs are widely used. Almost 10 percent of persons in the Netherlands used a non-aspirin NSAID in 1987, and the overall use was 11 defined daily doses per 1,000 persons.¹ In Australia in 1994, overall use was 35 defined daily doses per 1,000 persons, with 36 percent receiving NSAIDs for osteoarthritis, 42 percent for sprain and strain or low back pain, and 4 percent for rheumatoid arthritis. Thirty-five percent of the persons receiving NSAIDs were older than 60 years.²