Meta‐analysis: proton‐pump inhibition in high‐risk patients with acute peptic ulcer bleeding

Abstract
Recent data suggest that profound acid suppression may improve outcomes of patients in peptic ulcer bleeding. To better characterize the role of different pharmacological therapies in this population. MEDLINE was used to identify randomized trials (01/1990-04/2003) that assessed the efficacy of pharmacological treatments for patients with bleeding peptic ulcers exhibiting high-risk stigmata (Forrest Ia-IIb). Three groups of treatment were assessed: proton-pump inhibitors given as high-dose bolus followed by intravenous constant infusion (40-80 mg and at least 6 mg/h), high-dose oral proton-pump inhibitors (at least twice the standard dosage), non-high-dose proton-pump inhibitors (other proton-pump inhibitors dosing schedules). Mixed-effect models were used to determine rate differences between treatment and control groups. Eighteen studies (1855 patients) were included. High-dose intravenous proton-pump inhibitors significantly reduced rebleeding (-14.6%), surgery (-5.4%) and mortality (-2.7%) compared with placebo, and rebleeding (-20.6%) compared with H(2)RA. Compared with placebo, high-dose oral proton-pump inhibitors significantly reduced only rebleeding (-11.8%), while non-high-dose proton-pump inhibitor treatment significantly improved all three outcomes. High-dose intravenous proton-pump inhibitor significantly decreases ulcer rebleeding, surgery and mortality. Early data on high-dose oral proton-pump inhibitor suggest improved rebleeding. The non-high-dose proton-pump inhibitor regimens, including a broad range of dosing, also improved outcomes, suggesting that doses inferior to those in the high-dose intravenous proton-pump inhibitor may be effective.