Non-Steroidal Anti-Inflammatory Drugs For Osteoarthritis: Villains Or Heroes?

Osteoarthritis (OA) is the most common form of arthritis. It has been estimated that more than 20 million Americans are afflicted with OA, and that number will rise to 40 million by the year 2020.

In recent months there has been a contentious debate between cardiologists and rheumatologists regarding the use of non-steroidal anti-inflammatory drugs (NSAIDS) for OA. Behind this disagreement is controversy that exists as to the safest and most effective way of treating OA, particularly with respect to the use of NSAIDs, both non-selective and selective (so-called COX-2 selective agents or coxibs). Adverse reactions related to the gastrointestinal tract, particularly with the non-selective NSAIDs, have been described. And, more recently, concerns have been raised regarding cardiovascular events with both groups of agents.

A recent scientific statement from the American Heart Association (AHA) made recommendations with regard to the treatment of OA. (E.M. Antman, J.S. Bennett, A. Daugherty, C. Furberg, H. Roberts, K.A. Taubert, Use of nonsteroidal antiinflammatory drugs. An update for clinicians: a scientific statement from the American Heart Association, Circulation. 2007;113:2906-2913). The recommendations come in the form of â€oeguidelines.â€� These include:

•COX-2 inhibition can result in an increased risk for thrombosis due to increased activity of thromboxane A2 and reduced activity of prostacyclin. In addition, all NSAIDs can increase sodium and water retention, increasing the risk for exacerbations of hypertension and heart failure. Finally, COX-2 up-regulation may reduce myocardial ischemia and infarction during acute cardiac events, and inhibition of this isoenzyme can increase infarct size and lead to myocardial rupture.

•"Nonselective" NSAIDs also differ with regard to COX selectivity. Diclofenac has greater COX-2 selectivity than ibuprofen, which in turn has greater COX-2 selectivity compared with naproxen.

•Initial treatment of musculoskeletal pain should include nonpharmacologic therapy, including physical therapy, heat/cold, and orthotics. Acetaminophen and aspirin are probably the best initial choices for analgesia, although these agents should be used at the lowest possible dose for the shortest possible period.

•For patients who fail conservative therapy for musculoskeletal pain, NSAIDs may be chosen as a next step. Clinicians and patients should realize that the use of NSAIDs may slightly increase the risk for cardiovascular and cerebrovascular events. With this in mind, clinicians should try to use NSAIDs with lower selectivity for COX-2.

•Naproxen is probably the NSAID associated with the lowest risk for thrombosis. The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) questioned the safety of naproxen, but this trial had significant limitations.

•Patients with a history of gastrointestinal tract bleeding or who are at high risk for bleeding who require analgesia should be prescribed acetaminophen first. For these patients who require NSAID therapy, proton-pump inhibitors have been demonstrated to reduce the risk for recurrent gastrointestinal tract bleeding among patients receiving low-dose aspirin.

•Patients with active atherosclerotic processes are at increased risk for the thromboembolic complications of COX-2 inhibitors. Renal function and blood pressure should be monitored during treatment with COX-2 inhibitors.

•Ibuprofen, but not acetaminophen or diclofenac, appears to reduce the physiologic efficacy of aspirin in preventing thrombosis. Current recommendations call for delaying ibuprofen dosing until at least 30 minutes after taking aspirin or at least 8 hours prior to aspirin dosing.
The upshot? Use NSAIDS for OA as a last resort!

In an editorial in the journal, Osteoarthritis and Cartilage, a panel of arthritis research experts has vehemently- and not surprisingly- disagreed with these proposals.

The editorial summarizes the outcomes of an international workshop organized by the Osteoarthritis Research Society International (OARSI) and the International COX-2 Study Group, held 24--25 March 2007. (R.W. Moskowitz, S. Abramson, F Berenbaum, L.S.Simon, M. Hochberg, Coxibs and NSAIDS - Is the air any clearer? Perspectives from the OARSI international COX-2 workshop 2007, Osteoarthritis and Cartilage. 2007;15:849-856).

The authors urge that an evidence-based approach must be taken when making recommendations to patients.

The editorial questions the recommendation made in the AHA statement which described a stepped care approach to pharmacologic therapy for musculoskeletal diseases.

The authors also strongly recommend that several aspects of the AHA statement be reconsidered. For example, they urge that the AHA withdraw their non-evidence-based recommendations that high-dose aspirin be administered alone as a first line therapy for patients with chronic pain and arthritis.

Dr Roland W. Moskowitz, Professor of Medicine at Case Western Reserve University/University Hospitals of Cleveland and the lead author of the editorial commented, "Careful review of the pros and cons of using these agents, and the situations in which they are most safely and effectively used, is required to help us understand how best to take advantage of their availability".

The upshot of this whole discussion is that rheumatologists and cardiologists differ in their approach. It becomes an issue of â€oegut feelingâ€� versus evidence. What needs to be considered is not only data regarding cardiovascular risk which is still far from clear but also the effects on the quality of life for patients with OA. Stay tuned!