Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly population

Abstract

Objective. Acetaminophen is recommended as initial therapy for patients with arthritis, particularly those at increased risk of nonsteroidal antiinflammatory drug (NSAID)-induced gastrointestinal (GI) side effects. However, higher doses of acetaminophen inhibit prostaglandin synthesis and have been associated with GI events. This study was undertaken to compare the observed and adjusted rates of GI events (hospitalizations, ulcers, dyspepsia, GI prophylaxis) occurring with higher versus lower doses of acetaminophen.Methods. This was a retrospective cohort study of subjects ages >65 years who received a prescription for acetaminophen or NSAID between 1994 and 1996. Pharmaceutical and medical records were reviewed for 1 year of historical data prior to the index prescription of acetaminophen or non-aspirin NSAID. Risk factors for GI events were identified based on the historical data. To further control for bias, patients were categorized by propensity score (the likelihood of receiving acetaminophen, given defined risk factor values). Records were then reviewed for the duration of the index prescription or 30 days, whichever was less, to generate data on the occurrence of GI events. Determinants of acetaminophen utilization were identified using logistic regression, and rates of GI events for each therapy were examined using Poisson regression analyses, controlling for duration of exposure, individual risk factors, and propensity scores.Results. . Unadjusted rates of GI hospitalization, ulcer, and dyspepsia were higher for patients in the acetaminophen cohort than for those in the NSAID cohort. The occurrence of GI events in acetaminophen-treated patients was dose dependent, with rate ratios (compared with high-dose NSAIDs and adjusted for risk susceptibility) ranging from 0.6 (95% confidence interval 0.5-0.7) for <650 mg/day to 1.0 (0.9-1.1) for >3,250 mg/day.Conclusion. In this cohort, acetaminophen utilization is more common in patients at higher risk of GI events. After adjustment for risk susceptibility, patients receiving higher doses of acetaminophen have higher rates of GI events compared with those receiving lower doses.Practice guidelines endorsed by the American College of Rheumatology (ACR) recommend acetaminophen (up to 4 gm/day) as initial therapy for the treatment of arthritis (1,2), to avoid the gastrointestinal (GI) toxicity attributable to conventional nonsteroidal antiinflammatory drugs (NSAIDs) (3-9). Acetaminophen can also be used for patients with a history of NSAID intolerance or GI disease. (1,2,10) Recognized risk factors for GI events include age Ͼ65 years, previous GI disease, concomitant use of corticosteroids or anticoagulants, and comorbidities (3,8,9,11,12).However, several studies have associated acetaminophen with increased dyspepsia (13-15), and at Supported by Pfizer Inc.

Do proton‐pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?

“…The RAMQ and Med-Echo databases are linkable through a unique patient identifier. These databases have been used in previous studies (14,15) and have been shown to be valid for pharmacoepidemiologic research (16).…”

“…We chose that period to be 25% of the exposure duration and tested this choice in a sensitivity analysis. Most prescriptions for NS-NSAIDs and celecoxib in Quebec are dispensed with a medication supply for Յ30 days (14,15). Extending the exposure period by 25% of the number of supplied days means that GI hospitalizations that occurred during therapy or up to a week immediately following that therapy would be accounted for.…”

Acetaminophen not associated with gastrointestinal toxicity: Comment on the article by Rahme et al

“…The rate of dyspepsia symptoms in the acetaminophen cohort appeared to be dose dependent (1). Thus, patients receiving a daily dose of acetaminophen exceeding 2,600 mg were found to have rates of GI events comparable with those observed in the NSAID cohort, even after adjustment for GI risk susceptibility (1).…”

“…In a retrospective cohort study, Rahme et al compared the rates of gastrointestinal (GI) events occurring with higher versus lower doses of acetaminophen (1). They concluded that patients receiving higher doses of acetaminophen have higher rates of GI events compared with those receiving lower doses.…”

Et tu, acetaminophen?

“…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 ϳ97% of elderly (age Ն65 years) patients in Quebec.…”