WITHDRAWN: Proton pump inhibitor treatment for acute peptic ulcer bleeding.
BACKGROUND
Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer (PU) bleeding yield conflicting results.


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


METHODS
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.


METHODS
RCTs of PPI treatment (oral or intravenous) compared with placebo or H(2)-receptor antagonist (H(2)RA) in acute bleeding from PU.


METHODS
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.


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 H(2)RA. 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.


CONCLUSIONS
PPI treatment in PU bleeding reduces rebleeding and surgery compared with placebo or H(2)RA, but there is no evidence of an overall effect on all-cause mortality.
Leontiadis
Grigorios I
GI
Department of Medicine, Division of Gastroenterology, McMaster University, 1200 Main Street West, HSC 4W8B, Hamilton, Ontario, Canada, L8N 3Z5.
Sharma
Virender Kumar
VK
Howden
Colin W
CW
D000208:Acute Disease; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002423:Cause of Death; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D010438:Peptic Ulcer Hemorrhage / Q000188:drug therapy* / Q000401:mortality; D054328:Proton Pump Inhibitors; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors