What is the best management of peptic ulcer disease?

Management of Peptic Ulcer Disease

The best management of peptic ulcer disease requires immediate proton pump inhibitor (PPI) therapy, testing and eradication of Helicobacter pylori if present, and discontinuation of NSAIDs/aspirin when possible, as this approach reduces mortality from 8.6% for bleeding ulcers and 23.5% for perforated ulcers while preventing recurrence. 1, 2

Immediate Assessment and Risk Stratification

For uncomplicated peptic ulcer disease without alarm features (bleeding, perforation, obstruction) in patients under 60 years, proceed directly with PPI therapy and H. pylori testing rather than immediate endoscopy. 3 However, if the patient presents with hematemesis, melena, hemodynamic instability, severe abdominal pain suggesting perforation, or persistent vomiting, urgent endoscopy is mandatory as hemorrhage carries 8.6% mortality and perforation carries 23.5% mortality. 1

For bleeding peptic ulcers specifically, stabilize hemodynamics first with intravenous fluid resuscitation and blood products before endoscopy, then perform urgent endoscopy for both diagnosis and therapeutic hemostasis. 4 Administer pre-endoscopy erythromycin 250 mg IV to improve gastric visualization and reduce need for repeat endoscopy. 4, 3

Pharmacological Management: PPI Therapy

For Uncomplicated Peptic Ulcer Disease

Start omeprazole 20 mg once daily (or equivalent PPI) for duodenal ulcers, continuing for 4 weeks; some patients may require an additional 4 weeks. 5 For gastric ulcers, use omeprazole 40 mg once daily for 4-8 weeks, as gastric ulcers larger than 2 cm may require the full 8 weeks. 5, 2 This approach heals 80-100% of peptic ulcers within the specified timeframe. 2

For Bleeding Peptic Ulcers (High-Risk)

After successful endoscopic hemostasis, administer 80 mg PPI bolus immediately, followed by 8 mg/hour continuous intravenous infusion for 72 hours. 1, 4, 6 This high-dose protocol is critical as 60-76% of rebleeding episodes occur within the first 72 hours. 4, 3

After completing the 72-hour infusion, switch to oral PPI 40 mg twice daily for the next 11 days (completing 14 days total of high-dose therapy), which reduces rebleeding risk by 63% compared to once-daily dosing. 3 Then reduce to 40 mg once daily and continue for a total duration of 6-8 weeks to allow complete mucosal healing. 4, 6, 3

A critical pitfall: PPIs do not replace urgent endoscopy in patients with active bleeding—endoscopy remains essential for both diagnosis and therapeutic intervention. 4, 3

Helicobacter pylori Testing and Eradication

Test all patients with peptic ulcer disease for H. pylori infection before discharge using urea breath test (88-95% sensitivity, 95-100% specificity) or stool antigen test (94% sensitivity, 92% specificity). 1, 3 Avoid serology as it cannot distinguish active from past infection. 3

Important caveat: Tests for H. pylori have increased false-negative rates during acute bleeding episodes due to the bleeding itself and high-dose PPI therapy, so repeat testing 4-8 weeks after the bleeding episode if initial results are negative. 4, 6, 3

First-Line Eradication Therapy

In areas with low clarithromycin resistance (<15%), use standard triple therapy for 14 days: 1, 3

• PPI standard dose (omeprazole 20 mg or equivalent) twice daily
• Clarithromycin 500 mg twice daily
• Amoxicillin 1000 mg twice daily (or metronidazole 500 mg twice daily if penicillin allergy)

Start eradication therapy after 72-96 hours of intravenous PPI administration when oral feeding is reintroduced. 1, 4

Alternative Therapy for High Clarithromycin Resistance

Use 10-day sequential therapy if compliance can be maintained and clarithromycin resistance is high: 1, 3

• Days 1-5: PPI twice daily + amoxicillin 1000 mg twice daily
• Days 6-10: PPI twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily

Second-Line Therapy

If first-line therapy fails, use 10-day levofloxacin-amoxicillin triple therapy: 1, 3

• PPI standard dose twice daily
• Levofloxacin 500 mg once daily (or 250 mg twice daily)
• Amoxicillin 1000 mg twice daily

Document H. pylori eradication after treatment completion, as successful eradication reduces ulcer recurrence from 50-60% to 0-2%. 3, 2, 7 Failure to eradicate leads to recurrence rates of 40-50% over 10 years. 3

NSAID and Aspirin Management

Immediately discontinue all NSAIDs and aspirin when peptic ulcer is diagnosed, as this heals 95% of ulcers and reduces recurrence from 40% to 9%. 4, 3, 2 This single intervention is one of the most powerful in preventing recurrence.

If NSAIDs Must Be Continued

When NSAIDs cannot be discontinued for valid medical reasons: 3, 2

• Switch to a selective COX-2 inhibitor (celecoxib) or lower-risk nsNSAID (ibuprofen)
• Combine with long-term PPI therapy (omeprazole 20-40 mg daily)
• Test for and eradicate H. pylori if present, as eradication in NSAID users reduces peptic ulcer likelihood by 50%

For Patients Requiring Aspirin for Cardiovascular Disease

Restart aspirin within 1-7 days (ideally 1-3 days) once hemostasis is achieved, combined with PPI therapy. 6 The combination of PPI with aspirin reduces GI bleeding risk while maintaining cardiovascular benefits. 3

Follow-Up and Monitoring

For gastric ulcers specifically, perform follow-up endoscopy at 6 weeks to confirm healing and exclude malignancy, as gastric ulcers carry risk of underlying malignancy. 6 This is mandatory for gastric ulcers but not required for duodenal ulcers. 6

Hospitalize patients who undergo endoscopic hemostasis for high-risk stigmata (active arterial bleeding, visible vessels, adherent clots) for at least 72 hours. 4, 3 If rebleeding occurs despite optimal medical and endoscopic therapy, seek surgical consultation or consider percutaneous angiographic embolization. 4

Duration of PPI Therapy

For uncomplicated duodenal ulcer with successful H. pylori eradication: 6-8 weeks total, then discontinue PPI as rebleeding becomes extremely rare. 4, 6

Continue indefinite PPI therapy only for: 6, 3

• Chronic NSAID users who cannot discontinue (use with COX-2 inhibitor)
• Aspirin users with cardiovascular disease
• Patients with recurrent ulcers despite H. pylori eradication

Surgical Intervention

For perforated peptic ulcers or intractable bleeding unresponsive to endoscopic therapy, surgical intervention becomes necessary. 1 Perforation is the most common indication for emergency operation and causes about 40% of all ulcer-related deaths. 1 Successful management involves prompt recognition, resuscitation, appropriate antibiotic therapy, and timely surgical treatment. 1

Common Pitfalls to Avoid

• Never use potassium-competitive acid blockers (P-CABs like vonoprazan) as first-line therapy due to higher costs, limited availability, and less robust long-term safety data compared to PPIs. 3
• Do not rely on initial negative H. pylori testing during acute bleeding—repeat testing outside the acute context is essential. 4, 6
• Do not continue maintenance PPI therapy indefinitely without indication—discontinue after documented H. pylori eradication and NSAID cessation unless specific risk factors persist. 6, 3
• For gastric ulcers, never skip follow-up endoscopy—malignancy must be excluded. 6