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Classic Literature

The Case for PPI Use with Peptic Ulcer Disease

By Bradley A. Sharpe, MD

Lau JY, Sung JJ, Lee KK, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med. 2000;343:310-316.

Background: Many patients with acute upper gastrointestinal bleeding (UGIB) are treated empirically with intravenous proton pump inhibitors (PPI) prior to endoscopy. The literature supporting this practice has been limited and its widespread adoption likely reflects extrapolation from studies with limited inclusion criteria.

Methods: Researchers at a single institution in Hong Kong undertook a prospective, randomized, double-blind, placebo-controlled trial of high-dose PPIs in the treatment of peptic ulcer disease. All patients with acute UGIB underwent endoscopy within 24 hours of admission. Those with high-risk ulcers (active bleeding or visible vessel) underwent local therapy with epinephrine and thermocoagulation. Those with high-risk ulcers were then randomized to receive a 72-hour infusion of intravenous omeprazole or placebo. All patients subsequently received eight weeks of oral PPI. The researchers measured re-bleeding rates, need for emergent surgery, and mortality at 30 days.

Results: Of 739 patients with UGIB, 267 were found to have high-risk ulcers. Twenty-seven were excluded from randomization because of early emergent surgery or terminal disease. A total of 240 patients were randomized and followed for 30 days. At 30 days, re-bleeding rates were 22.5% (27/120) in the placebo-treated group versus 6.7% (8/120) in the omeprazole group (p<0.001). The majority of re-bleeding occurred in the first three days. Rates of necessary surgery and death were higher in the placebo group at 30 days, but not statistically significantly so. There were no adverse events noted.

Discussion: This landmark trial in 2000 put intravenous PPIs on the map, presenting strong evidence for their use in the management of peptic ulcer disease. In the trial, the number needed to treat to prevent one episode of re-bleeding was six. Most importantly for the current practice of hospitalists, though, are not the impressive results but instead the strict inclusion criteria. None of the patients were treated with acid suppression prior to endoscopy and only those patients with high-risk ulcers (active bleeding or visible vessel) were randomized. There have been no high-quality trials examining the blanket empiric use of PPIs—either oral or intravenous—prior to endoscopy in all patients with UGIB. A multi-disciplinary consensus statement published in the Annals of Internal Medicine in 2003 makes empiric PPI therapy before EGD a class C recommendation (poor evidence to support).

Hospitalists should be aware there are very limited data supporting the routine use of intravenous PPIs in the initial empiric management of UGIB. The intravenous formulations are expensive and like any pharmacologic therapy, there are risks of adverse reactions. While we await higher-quality studies, many experts in the field recommend oral PPIs in low-risk patients and intravenous PPIs in high-risk (ICU) patients prior to EGD. All argue, though, that PPI therapy should be stopped in the absence of high-risk ulcers at endoscopy, unless otherwise indicated.