A 48-year-old woman on chronic NSAIDs for rheumatoid arthritis develops a gastric ulcer. She is H. pylori-negative on serology. Regarding the management and pathophysiology of NSAID-induced peptic ulcer disease, all of the following are correct EXCEPT:

Explanation

## NSAID-Induced Peptic Ulcer Disease **Key Point:** PPIs and misoprostol are both effective for preventing NSAID-induced ulcers, but **PPIs are superior** in terms of efficacy and tolerability. Misoprostol is less commonly used due to side effects (diarrhea, abdominal cramps). ### Prevention Strategies for NSAID-Induced Ulcers | Strategy | Efficacy | Tolerability | Notes | |---|---|---|---| | **PPI (e.g., omeprazole 20 mg daily)** | Excellent (>95%) | Excellent | First-line; well-tolerated | | **Misoprostol (200 µg QID)** | Excellent (~95%) | Poor | Diarrhea, cramping limit compliance | | **H2-blocker (e.g., famotidine)** | Moderate (~70%) | Good | Less effective than PPI | | **COX-2 selective inhibitor** | Good (~80%) | Good | Lower GI risk but cardiovascular concerns | **High-Yield:** In meta-analyses and clinical trials, **PPIs are equivalent or superior to misoprostol** for both prevention and healing of NSAID-induced ulcers, with significantly better tolerability. ### Why Each Statement Is Correct (Except #1) **Statement 1 — COX-2 selective inhibitors have lower ulcer risk:** - **This is TRUE** — Celecoxib and other COX-2 inhibitors reduce GI complications by ~50% vs. non-selective NSAIDs - However, they carry increased cardiovascular risk (MI, stroke) - Used selectively in high-risk GI patients with acceptable CV risk **Statement 2 — Misoprostol superior to PPIs:** - **FALSE** — This is the incorrect statement - PPIs are at least as effective as misoprostol for prevention and healing - PPIs have superior tolerability (misoprostol causes diarrhea in 15–30%) - PPIs are now first-line for NSAID ulcer prevention - Misoprostol is a prostaglandin analog that increases mucosal protection and reduces acid, but GI side effects limit use **Statement 3 — Gastric ulcers more common than duodenal with NSAIDs:** - **TRUE** — NSAIDs preferentially cause gastric ulcers (~70% of NSAID ulcers) - H. pylori-induced ulcers more commonly affect the duodenum - This is a key distinguishing feature in the clinical vignette **Statement 4 — Discontinuation of NSAID is most effective:** - **TRUE** — Stopping the offending NSAID is the gold standard - Ulcers heal rapidly once the NSAID is withdrawn - If NSAID continuation is necessary, combine with PPI or COX-2 inhibitor **Clinical Pearl:** In an H. pylori-negative patient with NSAID-induced ulcer, the priority is NSAID cessation + PPI therapy. If NSAIDs must be continued (e.g., severe RA), switch to a COX-2 inhibitor or add a PPI. **Mnemonic:** **PPIS > MISO** — PPIs are preferred over misoprostol for NSAID ulcer prevention due to superior efficacy and tolerability.