HEALTH-SYSTEM EDITION
CLINICAL TWISTERS

Osteoarthritis dilemma

A 70-year old male with osteoarthritis has been hospitalized with a bleeding NSAID-induced ulcer. His history includes coronary heart disease with myocardial infarction at age 65. With bleeding stopped, current medications include lansoprazole 30 mg q.d. and metoprolol 50 mg q.d. His physician now needs to prescribe some medication to control osteoarthritis pain and inflammation for the patient to take once he is home. (The patient had previously taken naproxen 500 mg b.i.d.). The physician is also pondering whether to resume aspirin 180 mg q.d., which was begun following myocardial infarction. She asks for a pharmacist consult. What recommendations would you make?

The patient should first be tried on acetaminophen or salsalate therapy. These agents might control pain without further risk of GI ulceration. Although NSAID-induced ulcer disease may be treated, it is preferable to stop NSAID therapy. Many patients, however, must remain on NSAIDs because of chronic pain. Additionally, with this patient's age and history, 81-325 mg of aspirin daily would be advisable.

Because this patient is at high risk for hemorrhage and perforation from aspirin and NSAIDs, prophylaxis should be considered after treatment for acute ulcer. High-dose H₂-antagonists can prevent duodenal ulcers associated with NSAIDs. Misoprostol, 800 mcg/day, is another choice. Proton pump inhibitors, such as lansoprazole, can be used to heal and prevent NSAID-induced ulcers. They have higher healing rates than the H₂-antagonists.

Although COX-2 selective agents (rofecoxib and celecoxib) were marketed with the claim that they significantly reduce GI toxicities, recent evidence from the Celecoxib Arthritis Safety Study (CLASS) indicates long-term data (> six months) showing no benefit in GI toxicity was withheld in favor of short-term data (six months) which did.

Reevaluation of CLASS study and the Vioxx Gastrointesti-nal Outcomes Research Study (VIGOR) data indicates patients taking COX-2 inhibitors may have a greater risk for cardiovascular events. VIGOR included more than 8,000 participants with rheumatoid arthritis but excluded patients taking daily aspirin therapy. Twice as many patients taking rofecoxib had cardiovascular events than those taking naproxen.

CLASS included more than 8,000 patients with osteoarthritis and allowed daily aspirin therapy. Nevertheless, more patients taking celecoxib had cardiovascular events (not statistically significant). Physiologically, this makes sense, as COX-1 induces platelet aggregation.

It is not known how adding aspirin to COX-2 inhibitor therapy affects the risk of GI toxicity; even low-dose aspirin affects the COX-1 enzyme. CLASS suggests patients taking celecoxib and aspirin have a higher risk of cardiovascular events than those taking aspirin and NSAIDs. The CLASS trial also demonstrated that celecoxib with aspirin does not have a reduced risk of GI toxicity.

If acetaminophen or salsalate is ineffective for pain relief, continue a proton pump inhibitor plus naproxen. Regardless, continue one aspirin per day.

Jannet M. Carmichael, Pharm.D., FCCP, BCPS
Clinical Pharmacy Coordinator
VA Sierra Nevada Health Care System, Reno
Associate Professor of Medicine
University of Nevada, School of Medicine

For this patient's osteoarthritis pain, consider a therapeutic trial of acetaminophen 1,000 mg q.i.d. Acetaminophen is considered first-line therapy due to its efficacy, favorable side-effect profile, and low cost. The patient may also benefit from topical capsaicin. Depending on which joints are affected, nonpharmacologic options may also be appropriate, including reducing joint loading; weight loss; occupational therapy; and physical therapy including an exercise program to maintain range of motion, muscle strength, and general health.

Patients suspected of NSAID-induced ulcers should be tested for H. pylori. If infected, eradication therapy facilitates ulcer healing and reduces recurrence.

In general, the benefits of low-dose aspirin prophylaxis for patients with known coronary artery disease substantially outweigh risks of major bleeding. However, because NSAIDs can delay ulcer healing and contribute to bleeding, it is reasonable to temporarily withhold aspirin for six to eight weeks. Aspirin can be reintroduced at 81 mg q.d. Although probably not necessary with naproxen discontinued and aspirin dose reduced, co-therapy with a proton pump inhibitor would reduce risk of NSAID-induced ulcers and recurrent bleeding.

Elizabeth A. Chester, Pharm.D., BCPS
Clinical Pharmacy Specialist, Primary Care
Kaiser Permanente Colorado Region
Adjoint Assistant Professor
University of Colorado School of Pharmacy

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Kathy Hitchens. CLINICAL TWISTERS.

Drug Topics

2002;6:hse20.