Landmark Developments in Gastroenterology

A 20-Year Review

David A. Johnson, MD


June 20, 2015

In This Article

Gastroesophageal Reflux Disease and Proton Pump Inhibitors

The treatment of gastroesophageal reflux disease (GERD) has been transformed since the introduction of the first proton pump inhibitor (PPI) into clinical trials. Its superior efficacy in the treatment of GERD over conventional therapy with histamine-2 antagonists redefined the standard of care for patients with moderate to severe GERD. This treatment class has changed the natural history of GERD and its related complications, particularly recurrent esophageal strictures.

When I was in training in the early 1980s, we had stricture dilation clinics where patients would come in on a regular basis for esophageal dilation because of ineffective control of GERD. Some patients were even doing their own bougienage dilations at home. Today, refractory esophageal strictures due to GERD are virtually never seen, which is clearly due to effective therapy with PPIs.

This class of drugs has progressed through a number of advances to further enhance prolonged acid reduction, including the development of isomers of the racemate index agent (eg, esomeprazole from omeprazole, dexlansoprazole from lansoprazole) to take advantage of metabolic pathways that provide more predictable and slower clearance. Dual delayed-release formulations (ie, dexlansoprazole) provide a second release of the compound 4-6 hours after the initial dose. This second release provides a pharmacodynamic effect on gastric pH that is similar to twice-daily PPI dosing, which is believed to be needed in approximately 25% of patients.

Additionally, the concomitant use of PPIs in patients at risk for gastroduodenal ulcers and complications due to nonsteroidal anti-inflammatory drugs (NSAIDs) has had a profound effect on risk reduction and related clinical complications. These adverse gastrointestinal outcomes have resulted in significant morbidity and mortality. It has been reported that as many as 25% of chronic NSAID users will develop ulcer disease,[1] and 2%-4% will have major complications of bleeding or perforation of the stomach or intestine.[2] In the late 1990s, it was recognized that these gastrointestinal events resulted in more than 100,000 hospital admissions annually in the United States and 7000-10,000 deaths, especially among those who had been designated as high risk. In fact, in 1997, NSAID-related complications were a recognized leading cause of death in the United States, essentially equal to the rate of death from AIDS.[3]

PPIs have had an amazing impact on mitigating the risk of common upper gastrointestinal disease complications.


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