Clinical Evidence Concise
A Publication of BMJ Publishing Group
Nonsteroidal Anti-inflammatory Drugs
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Am Fam Physician. 2006 Feb 1;73(3):507-508.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been systematically reviewed by an AAFP-approved source. The evidence is available at http://www.clinicalevidence.com/ceweb/conditions/msd/1108/1108/jsp.
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 However, the COX-2 inhibitor rofecoxib was withdrawn from the market in 2004 after it was found to increase the risk of myocardial infarction, and there is good evidence that other COX-2 inhibitors also may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.
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.
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.
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.
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
1. Leufkens HG, Ameling CB, Hekster YA, et al. Utilization patterns of non-steroidal anti-inflammatory drugs in an open Dutch population. Pharm Weekbl Sci. 1990;12:97–103.
2. McManus P, Primrose JG, Henry DA, et al. Pattern of non-steroidal anti-inflammatory drug use in Australia 1990–1994. A report from the drug utilization subcommittee of the pharmaceutical benefits advisory committee. Med J Aust. 1996;164:589–92.
editor’s note: Paracetamol is called acetaminophen in the United States.
search date: December 2004
Adapted with permission from GØtzsche PC. Non-steroidal anti-inflammatory drugs. Clin Evid Concise 2005;14:388–9.
This is one in a series of chapters excerpted fromClinical Evidence Concise, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom.Clinical Evidence Concise is published in print twice a year and is updated monthly online. Each topic is revised every 12 months, and subscribers should view the most up-to-date version at http://www.clinicalevidence.com. If you are interested in contributing toClinical Evidence, please send an e-mail to CEcommissioning@bmj.com. This series is part of the AFP’s CME. See “Clinical Quiz” on page 387.
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