What is the recommended management protocol for a patient with peptic ulcer disease, possibly complicated by Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAIDs) use, and smoking?

Management Protocol for Peptic Ulcer Disease

Immediate Actions Upon Diagnosis

Immediately discontinue all NSAIDs and aspirin, initiate a proton pump inhibitor (PPI) at standard dosing (omeprazole 20-40 mg once daily or equivalent), and test for H. pylori infection with eradication therapy if positive. 1

• Counsel on complete smoking cessation, as smoking impairs ulcer healing and increases complication rates 1
• Avoid combining multiple NSAIDs, antiplatelet drugs, anticoagulants, or corticosteroids, as these dramatically increase gastric ulcer risk 1
• For uncomplicated ulcers, standard-dose PPI therapy (omeprazole 20-40 mg once daily) should be continued for 6-8 weeks to allow complete mucosal healing 2
• Take PPI 30 minutes before meals for optimal efficacy 1

H. pylori Testing and Eradication

Test all patients with peptic ulcer disease for H. pylori using noninvasive methods—urea breath test or stool antigen test are preferred over serology. 3, 1

First-Line Eradication Therapy

• Standard triple therapy for 14 days (if local clarithromycin resistance is <15%): 3, 4

  • 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 allergic)

• Bismuth quadruple therapy or concomitant therapy is preferred in areas with high clarithromycin resistance (>15%) 5

Sequential Therapy (Alternative for High Clarithromycin Resistance)

• Days 1-5: PPI standard dose twice daily + amoxicillin 1000 mg twice daily 3
• Days 6-10: PPI standard dose twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily 3

Second-Line Therapy (If First-Line Fails)

• 10-day levofloxacin-amoxicillin triple therapy: 3
  • PPI standard dose twice daily
  • Levofloxacin 500 mg once daily (or 250 mg twice daily)
  • Amoxicillin 1000 mg twice daily

Confirmation of Eradication

• Confirm H. pylori eradication 4-6 weeks after completing therapy using urea breath test or stool antigen test (not serology) 3, 1
• 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 3, 6
• After successful H. pylori eradication, maintenance PPI therapy is generally not necessary 1

NSAID-Associated Ulcer Management

If NSAIDs cannot be discontinued, continue omeprazole 40 mg once daily indefinitely for gastroprotection while on NSAIDs, and consider switching to a COX-2 selective inhibitor (celecoxib) plus PPI in high-risk patients. 1

• Discontinuing NSAIDs heals 95% of ulcers and reduces recurrence from 40% to 9% 7
• H. pylori eradication alone is insufficient to prevent NSAID-induced damage in patients with previous ulcer history; additional PPI therapy is mandatory 1
• Eradicating H. pylori in NSAID users reduces the likelihood of peptic ulcers by 50% 5
• High-risk patients (history of bleeding ulcer, age >65, concurrent anticoagulation/antiplatelet therapy) require intensive gastroprotection with PPI plus COX-2 inhibitor 1
• Use the lowest effective NSAID dose for the shortest duration possible 1

Management of Bleeding Peptic Ulcers

Acute Phase (First 72 Hours)

For patients with bleeding ulcers with high-risk stigmata who have undergone successful endoscopic therapy, administer 80 mg PPI bolus followed by 8 mg/hour continuous infusion for 72 hours. 3, 2

• Endoscopy is the first-line treatment for diagnosis and management of bleeding ulcers 2
• Pre-endoscopy erythromycin improves visualization and reduces the need for repeat endoscopy 2
• Most patients who undergo endoscopic hemostasis for high-risk stigmata should be hospitalized for at least 72 hours, as 60-76% of rebleeding episodes occur within this timeframe 2

Transition Phase (Days 4-14)

• Switch to oral PPI 40 mg twice daily for the next 11 days (completing 14 days total of high-dose therapy) after completing the 72-hour infusion 2, 6
• This reduces rebleeding risk by 63% compared to once-daily dosing in high-risk patients 2

Maintenance Phase (Weeks 3-8)

• Reduce to PPI 40 mg once daily after the initial 14 days and continue for a total duration of 6-8 weeks 6
• Continue oral PPI therapy for 6-8 weeks total to allow complete mucosal healing 2, 6

Addressing Underlying Causes in Bleeding Ulcers

• Test all patients for H. pylori infection and provide eradication therapy if confirmed positive, with documentation of cure 3, 6
• Immediately discontinue all NSAIDs and aspirin during the acute bleeding episode 6
• For patients requiring cardiovascular prophylaxis with aspirin, restart aspirin within 1-7 days (ideally 1-3 days) once hemostasis is achieved, along with PPI therapy 6

Follow-Up and Long-Term Management

Gastric Ulcers (Mandatory Follow-Up)

• Perform follow-up endoscopy approximately 6 weeks after hospital discharge to confirm ulcer healing and exclude malignancy 6
• This follow-up endoscopy is mandatory in gastric ulcers (unlike duodenal ulcers) due to the risk of underlying malignancy 6

Duodenal Ulcers

• Endoscopic confirmation of healing is not routinely necessary unless patient must continue NSAID therapy 1

Long-Term PPI Therapy Beyond 8 Weeks

• Discontinue PPI after documented H. pylori eradication, as rebleeding becomes extremely rare 6
• Maintain indefinite PPI therapy for: 6
  • NSAID-associated ulcers if NSAIDs must be continued (preferably with COX-2 inhibitor)
  • Aspirin users with cardiovascular disease
  • Patients with recurrent ulcers despite H. pylori eradication

Antiplatelet and Anticoagulation Management

• For patients with previous ulcer bleeding receiving single- or dual-antiplatelet therapy, use PPI therapy 3
• For patients with previous ulcer bleeding requiring continued anticoagulant therapy (vitamin K antagonists, DOACs), use PPI therapy 3
• Combining PPI with aspirin reduces GI bleeding risk while maintaining cardiovascular benefits 2

Critical Warnings and Pitfalls

• Do not use H2-receptor antagonists as first-line therapy, as they reduce duodenal ulcer risk but NOT gastric ulcer risk, making them inadequate for gastric ulcer treatment 1
• Poor compliance with PPI therapy increases NSAID-induced adverse events 4-6 fold; emphasize adherence 1
• Long-term PPI use may be associated with increased risks of pneumonia, hip fracture, Clostridium difficile infection, chronic kidney disease, and micronutrient deficiencies (magnesium, calcium, vitamin B12); use the lowest effective PPI dose for maintenance therapy 1, 5
• Failure to test for H. pylori can lead to recurrence rates of 40-50% over 10 years 2
• The combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold 5
• Seek surgical consultation for patients for whom endoscopic therapy has failed; percutaneous embolization can be considered as an alternative where available 3