Purpose: To evaluate whether proton pump inhibitors are more effective than
H-2-antagonists (H-2-A) for the treatment of bleeding peptic ulcer.
Data sources: PubMed database until January 2000. Study selection: Comparat
ive randomized trials of proton pump inhibitors (omeprazole, lansoprazole,
or pantoprazole) vs. H-2-A (cimetidine, ranitidine or famotidine).
Data extraction: Meta-analysis combining the odds ratios (OR) of the indivi
dual studies in a global OR (Peto method).
Outcomes evaluated: Persistent or recurrent bleeding, need for surgery, or
Data synthesis: Eleven studies fulfilled the inclusion criteria and contain
ed data for at least one of the planned comparisons. Persistent or recurren
t bleeding was reported in 6.7% (95% CI: 4.9-8.6%) of the patients treated
with proton pump inhibitors, and in 13.4% (95% CI: 10.8-16%) of those treat
ed with H2-A (OR 0.4; 95% CI: 0.27-0.59) (chi (2)-homogeneity test, 18; P =
0.09). Surgery was needed in 5.2% (95% CI: 3.4-6.9%) of the patients treat
ed with proton pump inhibitors, and in 6.9% (95% CI: 4.9-8.9%) of the patie
nts treated with H-2-A (OR 0.7; 95% CI: 0.43-1.13), Respective percentages
for mortality were 1.6% (95% CI: 0.9-2.9%) and 2.2% (95% CI: 1.3-3.7%) (OR
0.69; 95% CI: 0.31-1.57).
Sub-analysis: Five studies evaluated the effect of both therapies given in
bolus injections on persistent or recurrent bleeding rate, which was 6% (95
% CI: 3.6-8.3%) and 8.1% (95% CI: 5.3-10.9%), respectively (OR, 0.57; 95% C
I: 0.31-1.05). Persistent or recurrent bleeding in high risk patients (Forr
est Ia, Ib and IIa) occurred in 13.2% (95% CI: 7.9-8%) of the patients trea
ted with proton pump inhibitors and in 34.5% (27-42%) of those treated with
H-2-A (OR 0.28; 95% CT: 0.16-0.48), In patients not having endoscopic ther
apy, persistent or recurrent bleeding was reported, respectively, in 4.3% (
95% CI: 2.7-6.7%) and in 12% (95% CI: 8.7-15%) (OR 0.24; 95% CI: 0.13-0.43)
. Less marked differences were observed in patients having adjunct endoscop
ic therapy: 10.3% (95% CI: 6.7-13.8%) and 15.2% (11.1-19.3%) (OR 0.59; 95%
CI: 0.36-0.97). Moreover, the significance disappeared in this group when a
single outlier study was excluded.
Conclusions: Proton pump inhibitors are more effective than H-2-A in preven
ting persistent or recurrent bleeding from peptic ulcer, although this adva
ntage seems to be more evident in patients not having adjunct sclerosis the
rapy. This beneficial effect seems to be similar or even more marked in pat
ients with Forrest Ia, Ib or IIa ulcers. However, proton pump inhibitors ar
e not more effective than H-2-A for reducing surgery or mortality rates. Ne
vertheless, the data are too scarce and heterogeneous to draw definitive co
nclusions, and further comparative trials are clearly warranted.