What's the best Proton Pump Inhibitor (PPI) to start with for heartburn?

Best PPI to Start with for Heartburn

Start with standard-dose omeprazole 20 mg once daily or lansoprazole 30 mg once daily, taken 30-60 minutes before meals, as these are the most evidence-based and cost-effective first-line PPIs for heartburn. 1, 2

First-Line PPI Selection

• Omeprazole 20 mg once daily is the most widely studied PPI with the strongest evidence base and is recommended as initial therapy by the American Gastroenterological Association 1, 2

• Lansoprazole 30 mg once daily is an equally acceptable alternative with comparable efficacy to omeprazole 2, 3

• All PPIs as a drug class are superior to H2-receptor antagonists, which are in turn superior to placebo for treating heartburn 1

• Take the PPI 30-60 minutes before meals (typically before breakfast) to ensure the medication is present when postprandial acid secretion peaks 1, 2, 4

Why Not Higher-Potency PPIs Initially?

• Esomeprazole 40 mg and rabeprazole 40 mg are more potent (esomeprazole 20 mg = 32 mg omeprazole equivalent; rabeprazole 20 mg = 36 mg omeprazole equivalent), but should be reserved for step-up therapy rather than initial treatment due to higher cost without proven superiority in treatment-naive patients 1

• The evidence for starting with higher-potency PPIs comes primarily from H. pylori eradication studies, not simple heartburn management 1

Dosing Timeline and Response Assessment

• Assess symptom response at 4-8 weeks after initiating standard-dose once-daily PPI therapy 2

• Onset of antisecretory effect occurs within 1-2 hours, with maximum effect at 2 hours and duration lasting up to 72 hours 4, 3

• If heartburn resolves within the first week, this predicts sustained response (85% of patients heartburn-free on days 5-7 remain symptom-free at week 4) 2

Step-Up Approach for Inadequate Response

If standard once-daily dosing fails after 4-8 weeks:

• Increase to twice-daily dosing (e.g., omeprazole 20 mg twice daily or lansoprazole 30 mg twice daily) before meals 1, 2

• Expert consensus strongly supports twice-daily dosing for inadequate responders, even though most clinical trial data comes from once-daily studies 1

• Switching to a different PPI at standard dose is equally effective as doubling the dose of the original PPI (54.4% vs 57.5% heartburn-free days) 5

When to Stop Empiric Therapy

• Patients who fail twice-daily PPI therapy should be considered treatment failures and require objective testing (endoscopy, pH monitoring) rather than further dose escalation 1, 2

• The upper limit of empirical therapy is 8-12 weeks of twice-daily PPI dosing 1, 2

• Endoscopy in PPI treatment failures has low diagnostic yield—only 6.7% show erosive esophagitis compared to 30.8% in treatment-naive patients 6

Common Pitfalls to Avoid

• Do not start with P-CABs (vonoprazan, tegoprazan) as first-line therapy for uncomplicated heartburn—they should be reserved for documented PPI failures due to higher cost and limited long-term safety data 1, 2

• Do not use metoclopramide as monotherapy or adjunctive therapy—it is ineffective for heartburn based on fair evidence 1

• Do not prescribe cisapride—it has been withdrawn due to cardiac toxicity 1

• Do not add nighttime H2-receptor antagonists to twice-daily PPI therapy—there is no evidence this improves efficacy 1

Cost Considerations

• In the original Norwegian cost analysis, omeprazole 20 mg daily (NOK 18.90/day) and ranitidine 300 mg twice daily (NOK 18.80/day) had nearly identical costs, making the superior efficacy of PPIs the deciding factor 1

• Generic omeprazole and lansoprazole are now widely available and cost-effective, eliminating historical cost barriers to PPI use 1

Adjunctive Measures

• Antacids provide rapid symptom relief while awaiting PPI effect and can be used as needed for breakthrough symptoms 1, 2

• Elevate the head of the bed for patients with nighttime heartburn or regurgitation 1

• Avoid specific trigger foods (alcohol, coffee, spicy foods) only if they consistently provoke symptoms in that individual patient 1

• Weight loss is reasonable for overweight/obese patients as it may reduce long-term need for acid suppression 1

Prevalence of Partial Response

• Approximately 14-20% of GERD patients experience partial heartburn response to standard-dose PPI therapy (more common in non-erosive reflux disease at 19.9% than erosive esophagitis at 14.0%) 7

• Complete non-response to PPIs is rare (only 1.4-2.4% of patients) 7

• This means the vast majority of heartburn patients will respond adequately to standard-dose PPI therapy, supporting its use as first-line treatment 7