Proton pump inhibitor treatment for acute peptic ulcer bleeding.
BACKGROUND
Peptic ulcer (PU) bleeding is associated with substantial morbidity, mortality and healthcare cost. Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer bleeding have yielded conflicting results.


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


METHODS
We performed a search of CENTRAL, The Cochrane Library (Issue 3, 2003), MEDLINE (1966 to February 2003) and EMBASE (1980 to February 2003) and proceedings of recent major meetings through to February 2003. We searched the reference lists of articles and contacted pharmaceutical companies and experts in the field for additional published or unpublished data.


METHODS
RCTs of PPI treatment (oral or intravenous) compared with either placebo or H(2)-receptor antagonist (H(2)RA) in patients with acute bleeding from PU were included if they met pre-defined criteria.


METHODS
Two reviewers extracted data independently on a purpose-designed data extraction form. Validity of included studies was assessed by adequacy of randomisation method and other pre-defined criteria. Studies were summarised and meta-analysis was undertaken. The influence of factors on the outcomes was assessed.


RESULTS
Twenty-one RCTs with a total of 2915 participants were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.05), but not for mortality (P = 0.26) or surgery (P = 0.42). There was no significant difference in mortality rates between PPI and control treatment; pooled rates were 5.2% on PPI versus 4.6% on control (odds ratio (OR) 1.11; 95% CI 0.79 to 1.57). PPI treatment significantly reduced rates of surgical intervention compared with control; pooled rates were 8.4% on PPI versus 13.0% on control (OR 0.59; 95% CI 0.46 to 0.76). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI (range: 0% to 24.4%) versus 18.7% with control treatment (range: 2.3% to 39.1%), the OR was 0.46 (95% CI 0.33 to 0.64). Results on mortality and rebleeding rates were independent of route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. Surgical intervention rates varied with type of control (PPI significantly reduced surgical intervention rates compared with placebo and not when compared with H(2)RA) but not with route of PPI administration or application of initial endoscopic haemostatic treatment.


CONCLUSIONS
PPI treatment in PU bleeding reduces rebleeding and surgical intervention rates in studies comparing treatment with placebo or H(2)RA, but there is no evidence of an effect on mortality.
Leontiadis
G I
GI
McIntyre
L
L
Sharma
V K
VK
Howden
C W
CW
D000208:Acute Disease; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D010438:Peptic Ulcer Hemorrhage / Q000188:drug therapy*; D054328:Proton Pump Inhibitors; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors