Et tu, acetaminophen?

Acetaminophen is among the most commonly used of all medications, widely accepted as a safe and effective analgesic for mild-to-moderate pain. First prescribed for clinical use in 1893 by von Mering, acetaminophen did not appear commercially in the US until 1950 (1). It is now a frequent first-line choice for pain management in the elderly, particularly in patients with osteoarthritis (OA) (2–4). The rationale for this treatment approach has been based on the opinion that acetaminophen offers efficacy comparable with that of nonsteroidal antiinflammatory drugs (NSAIDs), with fewer side effects and less cost (2,4–6). Recently, there have been challenges to the recommendation that acetaminophen, rather than an NSAID, be prescribed for the initial treatment of OA (7,8). Two factors have contributed to this reevaluation. First, selective cyclooxygenase 2 (COX-2) inhibitors appear to have improved the gastrointestinal (GI) safety profile of conventional NSAIDs, a view that contributed to the modification, in 2000, of the American College of Rheumatology guidelines for the treatment of OA (3). Second, recent clinical trials and patient surveys indicate that NSAIDs provide superior efficacy in the treatment of OA, particularly among individuals with more severe symptoms and, possibly, in those with disease of the hip (7–11). However, even in studies that demonstrate superior efficacy of NSAIDs in the treatment of OA, many individuals (20–40%) report comparable or superior benefit from acetaminophen. Therefore, based on cost alone, it would not be unreasonable to continue to advocate initial use of acetaminophen in OA, provided that assumptions regarding its superior safety profile compared with NSAIDs are correct. In this issue of Arthritis & Rheumatism, Rahme and colleagues report the results of a retrospective cohort analysis that examined rates of adverse GI events in elderly patients treated with NSAIDs or acetaminophen (12). The authors utilized the Government of Quebec Health Care Fund database, which contains demographic, medical, and prescription information on 97% of elderly (age 65 years) patients in Quebec. The analysis included 21,000 patients who filled an acetaminophen prescription and 26,000 patients who had been prescribed an NSAID. The study period included the years 1994–1996, so the NSAID prescriptions were limited to nonselective agents. Study subjects were required to have 1 full year of observation in the database prior to enrollment, which was initiated by the first filled nonrenewal prescription for acetaminophen or non-aspirin NSAID. The database was searched for occurrence of GI events during only the duration of the prescription or 30 days, whichever was less. The provocative finding of the study was that patients taking higher doses of acetaminophen ( 2,600 mg/day) had higher rates of GI adverse events compared with those receiving lower doses. Indeed, when the data were adjusted for GI “risk susceptibility,” those taking high-dose acetaminophen experienced similar rates of GI events as did those taking high-dose NSAIDs. These findings are similar to those of Garcı́a Rodrı́guez and Hernandez-Diaz (13), in a recently reported nested case–control study that utilized the United Kingdom General Practitioners Research database. Those investigators reported that dosages of acetaminophen in excess of 2,000 mg/day conferred a risk for upper GI complications as great as that with traditional NSAIDs. High-dose acetaminophen increased the risk of GI adSteven B. Abramson, MD, New York University School of Medicine and the New York University–Hospital for Joint Diseases, New York, New York. Address correspondence and reprint requests to Steven B. Abramson, MD, 301 East 17th Street, New York, NY 10003. E-mail: steven.abramson@med.nyu. edu. Submitted for publication July 11, 2002; accepted July 19, 2002. Arthritis & Rheumatism