Clinical Twisters: Improving RA control post-MI

March 21, 2005

A 60-year-old woman, A.R., with rheumatoid arthritis for two years, is being discharged from your hospital after acute myocardial infarction (MI). She uses methotrexate (MTX) 30 mg weekly subcutaneously but still experiences joint pain and swelling; she takes naproxen regularly. Dismissal orders are nitroglycerin 0.4 mg sublingual p.r.n., metoprolol 25 mg, atorvastatin 40 mg, aspirin 162 mg, warfarin 2.5 mg (all q.d.); INR level twice weekly; lipid levels in six weeks. Her physician is pondering whether to add etanercept (Enbrel, Immunex) or another disease-modifying antirheumatic drug (DMARD) to MTX to better control RA. What do you recommend?

A 60-year-old woman, A.R., with rheumatoid arthritis for two years, is being discharged from your hospital after acute myocardial infarction (MI). She uses methotrexate (MTX) 30 mg weekly subcutaneously but still experiences joint pain and swelling; she takes naproxen regularly. Dismissal orders are nitroglycerin 0.4 mg sublingual p.r.n., metoprolol 25 mg, atorvastatin 40 mg, aspirin 162 mg, warfarin 2.5 mg (all q.d.); INR level twice weekly; lipid levels in six weeks. Her physician is pondering whether to add etanercept (Enbrel, Immunex) or another disease-modifying antirheumatic drug (DMARD) to MTX to better control RA. What do you recommend?

RA patients have an increased risk for MI. Those treated with MTX have demonstrated reduced MI incidence, but no data show whether other DMARDs or biologics impact cardiovascular outcomes.

I'd choose drug therapy based on RA activity, not MI history. However, because A.R. is on the one drug that may have an impact on cardiovascular risk in RA patients, I would be more in favor of adding a second DMARD, such as leflunomide (Arava, Aventis), sulfasalazine, or hydroxychloroquine, or perhaps a biologic agent, such as adalimumab (Humira, Abbott) or etanercept, depending on RA severity, rather than discontinuing MTX.

Arthur Schuna, M.S., FASHPClinical Pharmacy Coordinator William S. Middleton Memorial VA Medical Center Clinical Professor of Pharmacy University of Wisconsin Madison, Wis.

Before recommendation, consider the following: MTX duration, time at 30 mg, why SC instead of oral, naproxen dose, duration, which joints are painful/swollen, and how long an acute flare?

The initial concern is relief of joint pain and swelling. This may be done by arthrocentesis and corticosteroid injection(s) for major joint problems, and/or a short course of tapering oral corticosteroids.

Based on additional information obtained, consider the following: MTX is optimized. Other DMARDs (sulfasalazine and/or hydroxychloroquine) could be added; adding a biologic agent would be more aggressive and obtain a better outcome. TNF alpha-blockers (etanercept, adalimumab) could be used. Anakinra (Kineret, Amgen), an IL-1 receptor antagonist, would be less effective.

Concurrent MTX with NSAIDs has resulted in severe bone marrow suppression, aplastic anemia, and gastrointestinal toxicity from the MTX. Monitoring is important. The FDA now recommends naproxen limited to < 440 mg/day for 10 days pending further study following an NIH study showing use for up to three years increased the risk of strokes and heart attacks by 50%. Patients may be switched to acetaminophen, aspirin, or ibuprofen; acetaminophen is less effective for RA inflammation.

Aspirin 162 mg daily is appropriate post-MI; although later, a prophylactic dose will not interfere with INR levels. Consistent dosing and symptom and INR monitoring are necessary: Aspirin may decrease ibuprofen concentrations, warfarin interacts with NSAIDs or acetaminophen. Six months of atorvastatin (Lipitor, Pfizer) 40 mg daily has shown benefit in decreasing disease activity score for active RA in addition to affecting cardiac disease markers. For A.R. it may have a dual benefit.

Ralph E. Small, Pharm.D. Professor of Pharmacy and Medicine Virginia Commonwealth University Richmond, Va.