Effect of proton pump inhibitors on the outcomes of peptic ulcer bleeding: comparison of event rates in routine clinical practice and a clinical trial

Abstract

Objective. To assess clinical outcomes in patients treated with proton pump inhibitors (PPIs) after endoscopic hemostasis in routine clinical care, and to compare these outcomes to those seen in a randomized controlled trial (RCT) of i.v. esomeprazole. Materials and methods. Patients with peptic ulcer bleeding and endoscopic stigmata of recent hemorrhage, who were treated with i.v. esomeprazole or pantoprazole ≥120 mg/day following therapeutic endoscopy, were identified from 12 hospitals in Spain (n = 539). Outcomes assessed included further bleeding, all-cause mortality and surgery. The results were compared to those of the RCT. Results. Overall, 9.1% (95% confidence interval [CI]: 6.7–11.5) of patients experienced further bleeding within 72 h following initial endoscopy, 14.3% (95% CI: 11.3–17.2) of patients had further bleeding within 30 days and 3.3% (95% CI: 1.8–4.9) of patients died within 30 days. In the RCT, the rate of rebleeding within 72 h was significantly lower in the esomeprazole arm (5.9%) than in the placebo arm (10.3%; p = 0.026). The further bleeding rate in patients treated with esomeprazole in routine clinical practice (7.8%; 95% CI: 4.6–11.1) was between these two values. Similar results were seen with the other outcomes studied. Conclusions. The proportion of patients treated with i.v. esomeprazole in routine clinical practice who experienced further bleeding following endoscopic treatment for peptic ulcer bleeding was between the rates observed in the esomeprazole group and the placebo group in the RCT.

Key Words::

• peptic ulcer hemorrhage
• proton pump inhibitors
• randomized controlled trial

Declaration of interest: This study was funded by AstraZeneca. We acknowledge and thank Dr. Enrique Quintero, Dr. Senador Moran, Dr. Manuel Lopez Artimez, Dr. Rosa M^a Gómez Espín, Dr. Teresa Martínez Gimenez, Dr. Manuel Dominguez, Dr. Maria Badía, Dr. Enrique-Perez-Cuadrado, Dr. Katalin Aspuru, Pilar Sebastian and Saga Johansson for their help with the study in routine clinical practice. We also acknowledge and thank Susan Bromley and Catherine Hill from Oxford PharmaGenesis^™ Ltd who provided writing support funded by AstraZeneca R&D Mölndal. Angel Lanas has received grant/research support from Pfizer Inc. and AstraZeneca, fees for participating in advisory committees or review panels for Pfizer Inc., Bayer and Nicox, and fees for speaking or teaching from AstraZeneca. Luis A García Rodríguez has received grant/research support from AstraZeneca and Bayer Schering Pharma. Joseph JY Sung has received consulting fees from AstraZeneca Pharmaceuticals and fees for speaking or teaching from GlaxoSmithKline, Nycomed, Roche, AstraZeneca Pharmaceuticals and Novartis Pharmaceuticals. Xavier Calvet has received grant/research support from Oxoid Ltd and Janssen-Cilag, consultancy fees from Abbott Laboratories and Almirall Prodesfarma, fees for participating in advisory committees or review panels from AstraZeneca and Schering-Plough Corp., and fees for speaking or teaching from AstraZeneca, Schering-Plough Corp., Abbott Laboratories and Almirall Prodesfarma. Faust Feu has received consultancy fees and speaker fees from AstraZeneca. Julio Ponce has received grant/research support and consulting fees from AstraZeneca. Mónica Polo-Tomas, Santiago García, MaríaTeresa Arroyo Villarino, Angeles Perez-Aisa, Luis Bujanda and José L Calleja have no conflicts of interest to declare.

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