Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough

Gastroenterology. 2002 Mar;122(3):625-32. doi: 10.1053/gast.2002.31876.


Background & aims: Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue.

Methods: Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28.

Results: Eighteen controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time pH < 4 (P = 0.001). The administration of PPI + 1 day of H2RA was the only therapy that significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P < 0.001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily alone and either 1 week or 1 month of PPI + bedtime H2RA.

Conclusions: The combination of H2RA and PPI therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Ulcer Agents / administration & dosage
  • Drug Therapy, Combination
  • Female
  • Gastric Acid / metabolism*
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / metabolism*
  • Histamine H2 Antagonists / administration & dosage*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Omeprazole / administration & dosage
  • Prospective Studies
  • Ranitidine / administration & dosage*
  • Supine Position
  • Treatment Outcome


  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Ranitidine
  • Omeprazole