Expired CME Article

Treatment of Osteoarthritis

Authors: Elena V. Barnes, M.D., N Lawrence Edwards, M.D.

Abstract

Objectives: Although cyclooxygenase-2 inhibitors (coxibs) were developed to cause less gastrointestinal hemorrhage than nonselective nonsterodial antiinflammatory drugs (NSAIDs), there has been concern about their cardiovascular safety. The relative risk of acute myocardial infarction (AMI) was studied among users of celecoxib, rofecoxib, and NSAIDs in Medicare beneficiaries with a comprehensive drug benefit.


Methods: A matched case-control study was conducted of 54,475 patients 65 years of age or older who received their medications through two state-sponsored pharmaceutical benefits programs in the United States. All healthcare use encounters were examined to identify hospitalizations for AMI. Each of the 10,895 cases of AMI were matched to four controls on the basis of age, gender, and the month of index date. A matched logistic regression model was constructed, including indicators for patient demographics, healthcare use, medication use, and cardiovascular risk factors to assess the relative risk of AMI in patients who used rofecoxib compared with persons taking no NSAID, taking celecoxib, or taking NSAIDs.


Results: Current use of rofecoxib was associated with an elevated relative risk of AMI compared with celecoxib (OR 1.14; 95% CI, 1.05–1.46; P = 0.011), and with no NSAID (OR, 1.14; 95% CI, 1.00–1.31; P = 0.054). The adjusted relative risk of AMI was also elevated in dose-specific comparasions; rofecoxib ≤25 mg versus celecoxib ≤200 mg (OR 1.21; 95% CI, 1.01–1.44; P = 0.036) and rofecoxib >25 mg versus celecoxib >200 mg (OR 1.70; 95% CI, 1.07–2.71; P = 0.026). The adjusted relative risks of AMI associated with rofecoxib use of 1 to 30 days (OR, 1.40; 95% CI, 1.12–1.75; P = 0.005) and 31 to 90 days (OR, 1.38; 95% CI, 1.11–1.72; P = 0.003) were higher than >90 days (OR, 0.96; 95% CI, 0.72–1.25; P = 0.8) compared with celecoxib use of similar duration. Celecoxib was not associated with an increased relative risk of AMI in these comparisions.


Conclusions: In this study, current rofecoxib use was associated with an elevated relative risk of AMI compared with celecoxib use and no NSAID use. Dosages of rofecoxib greater than 25 mg were associated with a higher risk than dosages of 25 mg or less. The risk was elevated in the first 90 days of use, but not thereafter.


Key Points


* Osteoarthritis is the most common cause of chronic pain and disability in the US.


* Nonpharmacologic modalities are underutilized in the treatment of osteoarthritis.


* Weight loss is an important component in both the prevention of osteoarthritis and in the lessening symptoms.


* Pharmacologic therapy for osteoarthritis is directed at pain relief so that function can be maintained.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Minor MA, Hewett JE, Webel RR, et al. Efficacy of physical conditioning exercise in patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 1989;32:1396–1405.
 
2. Minor MA, Hewett JE, Webel RR, et al. Exercise tolerance and disease related measures in patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 1988;15:905–911.
 
3. Ettinger WH Jr, Burns R, Messier SP, et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis: the Fitness Arthritis and Seniors Trial (FAST). JAMA 1997;277:25–31.
 
4. Felson DT, Anderson JJ, Naimark A, et al. Obesity and knee osteoarthritis: the Framingham Study.Ann Intern Med 1988;109:18–24.
 
5. Felson DT, Zhang Y, Anthony JM, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women: the Framingham Study. Ann Intern Med 1992;116:535–539.
 
6. Minor MA. Exercise in the management of osteoarthritis of the knee and hip. Arthritis Care Res1994;7:198–204.
 
7. Warsi A, La Valley MP, Wang PS, et al. Arthritis self-management education programs: a meta-analysis of the effect on pain and disability. Arthritis Rheum 2003;48:2207–2213.
 
8. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum2000;43:1905–1915.
 
9. Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 1988;109:359–363.
 
10. Langman MJ. Treating ulcers in patients receiving anti-arthritic drugs. Q J Med 1989;73:1089–1091.
 
11. Roth S, Agrawal N, Mahowald M, et al. Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin. Arch Intern Med 1989;149:775–779.
 
12. Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307–314.
 
13. Bradley JD, Brandt KD, Katz BP, et al. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991;325:87–91.
 
14. Schnitzer TJ, Kamin M, Olson WH. Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study.Arthritis Rheum 1999;42:1370–1377.
 
15. Roth SH, Agrawal N, Mahowald M. Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis. J Rheumatol 1998;25:1358–1363.
 
16. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 1991;13:383–395.
 
17. Hollander JL. Intra-articular hydrocortisone in arthritis and allied conditions: a summary of two years’ clinical experience. J Bone Joint Surg Am 1953;35-A:983–990.
 
18. Gray RG, Gottlieb NL. Intra-articular corticosteroids: an updated assessment. Clin Orthop1983;177:235–263.
 
19. Raynauld JP, Buckland-Wright C, Ward R, et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial.Arthritis Rheum 2003;48:370–377.
 
20. Adams ME, Atkinson MH, Lussier AJ, et al. The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone.Osteoarthritis Cartilage 1995;3:213–225.
 
21. Altman RD, Moskowitz R. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial: Hyalgan Study Group. J Rheumatol1998;25:2203–2212.
 
22. Simon LS. Viscosupplementation therapy with intra-articular hyaluronic acid: fact or fantasy?Rheum Dis Clin North Am 1999;25:345–357.
 
23. da Camara CC, Dowless GV. Glucosamine sulfate for osteoarthritis. Ann Pharmacother1998;32:580–587.
 
24. Michalsen A, Moebus S, Spahn G, et al. Leech therapy for symptomatic treatment of knee osteoarthritis: results and implications of a pilot study. Altern Ther Health Med 2002;8:84–88.
 
25. Michalsen A, Klotz S, Ludtke R, et al. Effectiveness of leech therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 2003;139:724–730.
 
26. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331:889–895.
 
27. Pelletier JP, Caron JP, Evans C, et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 1997;40:1012–1019.
 
28. Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004;109:2068–2073.