What is the recommended management for a patient with peptic ulcer disease, possibly related to Helicobacter pylori (H. pylori) infection or Non-Steroidal Anti-Inflammatory Drug (NSAID) use?

Management of Peptic Ulcer Disease

Immediate Diagnostic and Treatment Priorities

All patients with peptic ulcer disease must be tested for H. pylori infection and receive eradication therapy if positive, while simultaneously discontinuing NSAIDs if applicable—these two interventions are the cornerstone of preventing recurrence and reducing mortality. 1, 2, 3

Initial Assessment and Risk Stratification

• Test all patients for H. pylori using noninvasive methods: urea breath test or stool antigen test are preferred over serology 2, 4
• Be aware that H. pylori tests have increased false-negative rates during acute bleeding episodes—if initial testing is negative during active bleeding, repeat testing after the acute phase 1, 2
• Identify NSAID use immediately and document aspirin use (including low-dose for cardiovascular protection), as this affects treatment strategy 2, 3
• For patients under 60 years without alarm symptoms (bleeding, perforation, weight loss, dysphagia), proceed with test-and-treat strategy rather than immediate endoscopy 2
• For patients 60 years and older or those with alarm symptoms, endoscopy is mandatory for diagnosis and risk stratification 2, 4

Primary Pharmacological Management

Standard PPI Therapy for Uncomplicated Ulcers

• Start omeprazole 20-40 mg once daily for duodenal ulcers (4-8 weeks) or gastric ulcers (6-8 weeks for complete mucosal healing) 2, 5, 6
• Alternative PPIs with equivalent efficacy: lansoprazole 30 mg daily, rabeprazole 20 mg daily, or esomeprazole 20-40 mg daily 2, 6
• Avoid pantoprazole when possible due to lower potency (40 mg pantoprazole equals only 9 mg omeprazole equivalent) 7
• Most duodenal ulcers heal within 4 weeks; gastric ulcers larger than 2 cm may require 8 weeks 5, 3

High-Dose PPI for Bleeding Ulcers

• For bleeding ulcers with high-risk stigmata after endoscopic hemostasis: administer 80 mg PPI bolus followed by 8 mg/hour continuous infusion for 72 hours 2, 8
• After 72 hours, transition to pantoprazole 40 mg twice daily for days 4-14, then switch to once-daily dosing 2
• This twice-daily regimen reduces rebleeding risk by 63% compared to once-daily dosing (RR 0.37, CI 0.19-0.73) in high-risk patients 2
• PPI infusion does not replace urgent endoscopy—endoscopy remains first-line for diagnosis and hemostasis 1, 2

H. pylori Eradication Regimens

First-Line Therapy (Low Clarithromycin Resistance Areas)

• Standard triple therapy for 14 days: PPI (standard dose twice daily) + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily 2, 5, 9
• This regimen achieves >90% eradication rates when clarithromycin resistance is low 6, 9
• Eradication reduces ulcer recurrence from 50-60% to 0-2% 2, 3

Alternative First-Line Therapy (High Clarithromycin Resistance or Bismuth Available)

• Bismuth quadruple therapy for 14 days (preferred when resistance patterns unknown): PPI twice daily + bismuth + metronidazole + tetracycline 2, 7, 4
• Concomitant 4-drug therapy (nonbismuth quadruple therapy) is an alternative when bismuth unavailable 2, 7

Second-Line Therapy After Treatment Failure

• Levofloxacin-amoxicillin triple therapy for 10 days: PPI twice daily + levofloxacin 500 mg once daily + amoxicillin 1000 mg twice daily 2
• Perform susceptibility testing if available after first-line failure; if clarithromycin resistance demonstrated, avoid clarithromycin-based regimens 5

Confirmation of Eradication

• Document H. pylori eradication 4-6 weeks after completing therapy using urea breath test or stool antigen test (not serology) 2, 8
• Failure to confirm eradication is a critical pitfall—persistent infection leads to 40-50% recurrence rates over 10 years 2

NSAID-Associated Ulcer Management

Immediate NSAID Management

• Discontinue all NSAIDs immediately when peptic ulcer diagnosed—this heals 95% of ulcers and reduces recurrence from 40% to 9% 2, 3
• This includes low-dose aspirin unless cardiovascular risk outweighs bleeding risk 2, 10
• Continue standard PPI therapy (omeprazole 20-40 mg daily) for 4-8 weeks even after NSAID discontinuation 2, 10

When NSAIDs Cannot Be Discontinued

• Switch to selective COX-2 inhibitor (celecoxib) combined with PPI therapy for ongoing gastroprotection 2, 4
• Alternative: use lowest-risk nonselective NSAID (ibuprofen) with PPI co-therapy 2
• Test for and eradicate H. pylori if present—eradication in NSAID users reduces peptic ulcer likelihood by 50% 2, 4
• Continue PPI therapy indefinitely as long as NSAID use continues 2, 10

Prevention Strategy for Chronic NSAID Users

• PPIs reduce NSAID-related ulcers by 90% and are superior to H2-receptor antagonists 7, 10
• H2-receptor antagonists (ranitidine, cimetidine) are inadequate—they only protect against duodenal ulcers, not gastric ulcers 8, 7
• Misoprostol 600-800 mg daily reduces gastric ulcers by 74% but causes diarrhea/abdominal pain in 20% of patients, limiting tolerability 7, 10

Long-Term Maintenance Therapy

After H. pylori Eradication

• Maintenance PPI therapy is generally not necessary after successful H. pylori eradication in patients who discontinue NSAIDs 8
• Exception: consider maintenance therapy up to 12 months in select high-risk cases (history of complications, recurrent ulcers despite eradication) 8

For Chronic NSAID Users

• Continue PPI indefinitely for patients requiring ongoing NSAID therapy who cannot discontinue 2, 8
• Consider repeat endoscopy to confirm healing before resuming NSAIDs in patients with complicated ulcers 8

For Idiopathic (H. pylori-Negative, NSAID-Negative) Ulcers

• These ulcers are increasingly common as H. pylori prevalence falls and are more aggressive with higher recurrence and bleeding risk 9, 10
• Long-term maintenance PPI therapy is recommended (often at half the healing dose) to prevent recurrence 10

Critical Pitfalls to Avoid

• Never use H2-receptor antagonists as first-line therapy—they are significantly less effective than PPIs for ulcer healing (80-100% healing with PPIs vs. lower rates with H2RAs) 8, 6, 3
• Do not use potassium-competitive acid blockers (vonoprazan) as first-line therapy—higher costs, limited availability, and less robust long-term safety data compared to PPIs 2
• Avoid combining multiple NSAIDs—this dramatically increases GI bleeding risk, especially when combined with aspirin 7
• Do not assume buffered or coated aspirin reduces GI risk—these formulations do not significantly decrease ulcer risk 7
• Never skip H. pylori eradication confirmation testing—relying solely on symptom resolution leads to persistent infection and complications 7
• Recognize that 60-76% of rebleeding episodes occur within 72 hours—patients with high-risk stigmata after endoscopic hemostasis should be hospitalized for at least 72 hours 2