What is the recommended treatment for a patient with Peptic Ulcer Disease (PUD), possibly caused by Helicobacter pylori infection or Non-Steroidal Anti-Inflammatory Drug (NSAID) use?

Treatment of Peptic Ulcer Disease

For patients with peptic ulcer disease, initiate proton pump inhibitor (PPI) therapy at standard doses (omeprazole 20-40 mg daily or equivalent) for 4-8 weeks, test all patients for H. pylori and provide eradication therapy if positive, and discontinue NSAIDs/aspirin whenever possible. 1, 2, 3

Initial Diagnostic and Treatment Approach

H. pylori Testing

• Test all patients with peptic ulcer disease for H. pylori infection using noninvasive methods (urea breath test or stool antigen test preferred over serology) 4, 5, 3
• For patients younger than 60 years without alarm symptoms, use the test-and-treat strategy rather than immediate endoscopy 2, 5
• Important caveat: Tests for H. pylori have increased false-negative rates during acute bleeding episodes, so repeat testing outside the acute context if initial results are negative 4, 1

PPI Therapy for Uncomplicated Ulcers

• Duodenal ulcers: Omeprazole 20 mg once daily (or equivalent PPI) for 4 weeks heals most ulcers; some patients may require an additional 4 weeks 6, 7, 3
• Gastric ulcers: Omeprazole 40 mg once daily (or equivalent PPI) for 4-8 weeks, as gastric ulcers require longer treatment duration than duodenal ulcers 6, 7, 3
• All PPIs show similar efficacy: Omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, or rabeprazole 20 mg daily are equally effective 7
• Take PPIs before meals for optimal efficacy 6

H. pylori Eradication Regimens

First-Line Treatment Options

Bismuth quadruple therapy or concomitant therapy (nonbismuth quadruple therapy) is preferred over clarithromycin-based triple therapy due to increasing clarithromycin resistance 2, 5

Standard triple therapy (use only in areas with low clarithromycin resistance <15%):

• Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 10-14 days 6, 8, 2
• If ulcer is present at initiation, continue omeprazole 20 mg once daily for an additional 18 days for ulcer healing 6

Alternative dual therapy (less effective, use only if triple therapy not feasible):

• Omeprazole 40 mg once daily + clarithromycin 500 mg three times daily for 14 days 6
• If ulcer present, add 14 additional days of omeprazole 20 mg once daily 6

Confirming Eradication

• Document H. pylori eradication after treatment completion to ensure successful therapy, as eradication reduces ulcer recurrence from 50-60% to 0-2% 4, 2, 3

NSAID-Associated Ulcers

Immediate Management

• Discontinue all NSAIDs and aspirin immediately when peptic ulcer is diagnosed, as this heals 95% of ulcers and reduces recurrence from 40% to 9% 4, 2, 3
• Initiate PPI therapy at standard doses for 4-8 weeks 1, 2
• Test for and eradicate H. pylori if present, as eradication in NSAID users reduces peptic ulcer likelihood by 50% 4, 5

When NSAIDs Cannot Be Discontinued

If NSAIDs must be continued for valid medical reasons:

• Switch to a selective COX-2 inhibitor (celecoxib) or lower-risk nsNSAID (ibuprofen) combined with PPI therapy 4, 2
• Maintain long-term PPI therapy for secondary prophylaxis 4, 1, 2
• Avoid combining multiple NSAIDs, aspirin, antiplatelet drugs, or anticoagulants whenever possible 4
• Use the lowest effective NSAID dose for the shortest duration 4

Critical warning: The combination of H. pylori infection and NSAID use synergistically increases bleeding ulcer risk more than sixfold 5

Management of Bleeding Peptic Ulcers

Acute Phase (First 72 Hours)

For high-risk stigmata after endoscopic hemostasis:

• Administer IV PPI with 80 mg bolus followed by 8 mg/hour continuous infusion for 72 hours 1, 2, 9
• This regimen significantly reduces rebleeding rates, need for surgery, and mortality 1, 9
• Pre-endoscopic PPI administration may reduce need for endoscopic therapy but does not improve mortality or rebleeding outcomes and should not delay urgent endoscopy 1, 2

Transition and Maintenance

• After 72-hour infusion, switch to oral PPI 40 mg twice daily for 11 days (completing 14 days total of high-dose therapy) 1
• Then reduce to standard dose (20-40 mg once daily) and continue for total duration of 6-8 weeks to allow complete mucosal healing 1, 2
• Most patients should be hospitalized for at least 72 hours, as 60-76% of rebleeding episodes occur within this timeframe 2

Special Considerations

Potassium-Competitive Acid Blockers (P-CABs)

• Do NOT use P-CABs (vonoprazan) as first-line therapy for peptic ulcer disease due to higher costs, limited availability, and less robust long-term safety data compared to PPIs 4, 2, 9
• P-CABs may be useful in PPI treatment failures, assuming ulcers are not secondary to non-acid causes (cancer, opportunistic infections, vasculitis, ischemia) 4, 9
• For H. pylori eradication specifically, P-CABs show superior or non-inferior results to PPIs, but cost considerations remain 4

Follow-Up for Gastric Ulcers

• Perform follow-up endoscopy at 6 weeks for all gastric ulcers to confirm healing and exclude malignancy 1
• This is mandatory for gastric ulcers (unlike duodenal ulcers) due to risk of underlying malignancy 1

Long-Term PPI Therapy

Discontinue PPI after 6-8 weeks unless:

• Chronic NSAID use that cannot be discontinued 1, 2
• Recurrent ulcers despite H. pylori eradication 2
• Aspirin users with cardiovascular disease requiring ongoing prophylaxis 1
• H. pylori-negative ulcers, which are more aggressive with high recurrence rates and may benefit from long-term PPI therapy 10

Potential risks of long-term PPI use include fractures, interaction with antiplatelet medications, chronic kidney disease, C. difficile infection, and micronutrient deficiencies (magnesium, calcium, vitamin B12) 5

Aspirin in Cardiovascular Disease Patients

• For patients requiring cardiovascular prophylaxis with aspirin who develop bleeding ulcers, restart aspirin within 1-7 days (ideally 1-3 days) once hemostasis is achieved, along with PPI therapy 1
• Combining PPI with aspirin reduces GI bleeding risk while maintaining cardiovascular benefits 4