A Mechanism-Based Strategy to Prevent NSAID-Induced Gastrointestinal Injury: Step-down Switching to Acetaminophen Based on 1-Week Evaluation of NSAID Efficacy

Conventional strategies for preventing nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) injury have primarily focused on gastroprotective agents, particularly proton pump inhibitors (PPIs). However, PPIs do not fully prevent NSAID-induced GI injury and are associated with an increased risk of lower GI injury and various PPI-related adverse events. This review discusses clinical strategies to minimize NSAID exposure. Based on limited evidence, the following strategies are suggested: 1. Because the efficacy of NSAIDs for neuropathic or nociplastic pain (NNP) is limited, NSAIDs may be avoided in patients with predominantly NNP. 2. Prioritize topical NSAIDs or acetaminophen for mild pain. 3. Analgesic efficacy may be evaluated approximately 1 week after NSAID initiation. However, this evaluation may be delayed by up to 2 weeks. Patients referred from other institutions may be managed using the same evaluation time frame. 4. If pain is reduced at the time of evaluation, NSAIDs may be discontinued or switched to acetaminophen to reduce NSAID exposure, or once adequate pain relief is achieved, without waiting for 1 week. 5. If pain is not reduced at the time of evaluation, reevaluate the pain mechanism and consider modifying management: NNP-targeted agents may be considered if NNP predominates, or opioids or more potent NSAIDs if NcP predominates. In addition, adjunctive strategies—including topical NSAIDs, non-pharmacologic interventions, and Helicobacter pylori eradication therapy—may further contribute to reducing overall NSAID exposure. However, COX-2-selective NSAIDs do not sufficiently mitigate risks. These strategies were implemented in clinical practice, markedly reducing overall NSAID use without any reported cases of severe NSAID-induced GI injury in the author’s clinical experience. By focusing on the reduction of unnecessary NSAID exposure, this approach may serve as a practical strategy to prevent NSAID-induced GI injury and may additionally mitigate other NSAID-related adverse events, including renal impairment and cardiovascular events.