Proton pump inhibitor treatment for acute peptic ulcer bleeding

 

Abstract

Background

Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer (PU) bleeding yield conflicting results.

Objectives

To evaluate the efficacy of PPIs in acute bleeding from PU using evidence from RCTs.

Search strategy

We searched CENTRAL, The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), proceedings of major meetings to November 2004, and reference lists of articles. We contacted pharmaceutical companies and experts in the field.

Selection criteria

RCTs of PPI treatment (oral or intravenous) compared with placebo or H₂-receptor antagonist (H₂RA) in acute bleeding from PU.

Data collection and analysis

Two reviewers extracted data independently, assessed study validity, summarised studies and undertook meta-analysis. The influence of study characteristics on the outcomes was examined by subgroup analyses and meta-regression.

Main results

Twenty-four RCTs comprising 4373 participants in total were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.04), but not for all-cause mortality (P = 0.24) or surgery (P = 0.45). There was no significant difference in all-cause mortality rates between PPI and control treatment; pooled rates were 3.9% on PPI versus 3.8% on control (odds ratio (OR) 1.01; 95% CI 0.74 to 1.40). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI versus 17.3% with control treatment (OR 0.49; 95% CI 0.37 to 0.65). PPI treatment significantly reduced surgery compared with control; pooled rates were 6.1% on PPI versus 9.3% on control (OR 0.61; 95% CI 0.48 to 0.78). There was no evidence to suggest that results on mortality and rebleeding were dependent on study quality, route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. PPIs significantly reduced surgery compared with placebo but not when compared with H₂RA. There was no evidence to suggest that study quality, route of PPI administration or application of initial endoscopic haemostatic treatment influenced results on surgery. PPI treatment appeared more efficacious in studies conducted in Asia compared to studies conducted elsewhere. All-cause mortality was reduced only in Asian studies; reductions in rebleeding and surgery were quantitatively greater in Asian studies. Among patients with active bleeding or non-bleeding visible vessel, PPI treatment reduced mortality (OR 0.53; 95% CI 0.31 to 0.91), rebleeding and surgery.

Authors' conclusions

PPI treatment in PU bleeding reduces rebleeding and surgery compared with placebo or H₂RA, but there is no evidence of an overall effect on all-cause mortality.

 

Plain language summary

In people with a bleeding ulcer in the stomach or duodenum there is no evidence of a difference in the risk of death if they are treated with a proton pump inhibitor, or an H₂-receptor antagonist, or if they are given no specific drug treatment. However, proton pump inhibitors do reduce the risk of further bleeding and the need for surgery.

Bleeding from ulcers in the stomach or duodenum is a common medical emergency. Research has suggested that reducing the amount of acid in the stomach may help to control the bleeding. The review compared the effect of one type of anti-acid drug (proton pump inhibitor) with either no treatment (placebo) or with another type of anti-acid drug (H₂ receptor antagonist). Proton pump inhibitors reduced further bleeding from the ulcer and the need for surgery but overall the numbers of people who died were not lowered. It was not possible to find out why the reduction in further bleeding and surgery with proton pump inhibitors did not result in lower death rates.