Oral vs. Intravenous Proton Pump Inhibitors in Patients with Peptic Ulcer Bleeding

A recent meta-analysis indicates treatment with oral proton pump inhibitors (PPIs) produces outcomes similar to those obtained with treatment with intravenous PPIs in patients with peptic ulcer bleeding.

Although there have been several trials that compared head-to-head efficacy of oral and intravenous PPIs in peptic ulcer bleeding, they have involved relatively small numbers of patients and have featured “variations in entry criteria on bleeding stigmata, treatment responses between oral and intravenous PPIs, and time of outcome measures.”

To gain a clearer picture of the relative efficacy of these two forms of PPIs in this patient population, the authors of “Meta-analysis: Comparison of Oral vs. Intravenous Proton Pump Inhibitors in Patients with Peptic Ulcer Bleeding,” published in Alimentary Pharmacology & Therapeutics, conducted a literature search and identified six randomized controlled trials involving patients with peptic ulcer bleeding who received endoscopic therapy and were treated with either oral or intravenous PPIs. To be included in this study, trials had to report at least one of the following outcomes: recurrent bleeding, surgical intervention, or mortality.

The six studies included a total of 615 patients who were randomized to receive oral PPIs (n = 302) vs. intravenous PPIs (n = 313). The mean age of patients enrolled in the studies was 60 years, and 437 of the 615 patients were male (71%).

The authors reported that patients “showed a wide range of bleeding stigmata, including clean base ulcer (26%), flat/red spot (8%), adherent clot (19%), nonbleeding vessel (14%), visible vessel (10%), and active bleeding, including spurting and oozing vessel (23%).”

All patients received endoscopic procedures within 24 hours of admission for peptic ulcer bleeding. Patients received intravenous PPIs in the first three days following treatment, and then oral PPIs for 1-2 months after. In two trials, patients received twice-daily 40 mg doses of intravenous PPI; in the other four trials, patients received “high-dose” infusions of 80 mg once per day. Reported PPIs used included pantoprazole, omeprazole, rabeprazole, and lansoprazole.

In terms of primary outcomes, the authors wrote that “All trials reported recurrent bleeding. Heterogeneity among the trials was not statistically significant (P = 0.90) and the combined result showed no significant difference on the recurrent bleeding between the oral (8.6%) and intravenous (9.3%) PPIs groups (RR: 0.92, 95% CI: 0.56—1.50).”

There were no significant differences between oral vs. intravenous PPIs in terms of 15-day and 30-day recurrent bleeding in the trials that reported those outcomes.

Although there were also no significant differences between oral vs. intravenous PPIs in terms of mean volume of blood transfused, requirement of surgical intervention, and all-cause mortality, the researchers did find that patients who received treatment with oral PPIs spent significantly less time in the hospital compared with patients who received intravenous PPIs (−0.74 day, 95% CI: −1.10 day to −0.39 day).

Analysis of data from trials in which patients receive high-dose intravenous PPIs (80 mg intravenous bolus PPIs and 8 mg/h infusion) revealed no statistically significant difference in terms of recurrent bleeding, volume of blood transfused, length of hospital stay, and all-cause mortality.

In their discussion of these results, the authors wrote that “Intravenous PPIs showed no distinct advantage over the oral PPIs in terms of recurrent bleeding, volume of blood transfused, requirement of surgery, and overall mortality but extended hospital stay for intravenous infusion of medication.”

The authors concluded that, although this study “demonstrates that oral PPIs have similar clinical effectiveness,” these findings are limited by insufficient sample size. They recommend conducting a larger double-blinded controlled trial to confirm the non-inferior effectiveness of oral PPIs. In the meantime, they feel “it is worth considering a shorter term of IV PPIs with early conversion oral PPIs for those without the high risk of bleeding stigmata, so that patients can be discharged earlier after endoscopy.”