Potential for Drug–Drug Interactions in Patients Taking Analgesics for Mild-to-Moderate Pain and Low-Dose Aspirin for Cardioprotection

Millions of individuals in the United States take low-dose aspirin for cardioprotection. Physicians face a clinical dilemma when those same patients also have pain from arthritis or another condition. Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal (GI) complications when used in conjunction with aspirin. In addition, NSAIDs, particularly ibuprofen, may interfere with the antithrombotic benefits of aspirin through competitive interaction with platelet cyclooxygenase-1 (COX-1). Evidence suggests that naproxen has antithrombotic effects; however, as with other NSAIDs, it poses a risk of gastrotoxicity. Selective COX-2 inhibitors reduce the risk of GI side effects, and although they inhibit platelet COX-1, it is to a far lesser extent than COX-2. However, it is unclear to what degree COX-2 inhibitors remain gastroprotective in the presence of aspirin. In addition, recent long-term trials have raised concerns about adverse cardiovascular events with prolonged use of both traditional and selective NSAIDs. Conversely, acetaminophen is well tolerated, has not been shown to contribute to gastrotoxicity when taken with aspirin, and has not been shown to interfere with the inhibition of platelet aggregation produced by aspirin. Acetaminophen is considered a first-line therapy for patients with mild-to-moderate joint pain.