Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Jun 12;2013(6):CD007999.
doi: 10.1002/14651858.CD007999.pub2.

Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding

Ignacio Neumann  1 , Luz M Letelier, Gabriel Rada, Juan Carlos Claro, Janet Martin, Colin W Howden, Yuhong Yuan, Grigorios I Leontiadis
Affiliations
Meta-Analysis

Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding

Ignacio Neumann et al. Cochrane Database Syst Rev. .

Abstract

Background: Treatment with proton pump inhibitors (PPIs) improves clinical outcomes in patients with peptic ulcer bleeding. However, the optimal dose and route of administration of PPIs remains controversial.

Objectives: To evaluate the efficacy of different regimens of PPIs in the management of acute peptic ulcer bleeding using evidence from direct comparison randomized controlled trials (RCTs).We specifically intended to assess the differential effect of the dose and route of administration of PPI on mortality, rebleeding, surgical intervention, further endoscopic haemostatic treatment (EHT), length of hospital stay, transfusion requirements and adverse events.

Search methods: We searched CENTRAL (in The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (from inception to September 2010) and proceedings of major gastroenterology meetings (January 2000 to September 2010), without language restrictions. Original investigators were contacted to request missing data.

Selection criteria: RCTs that compared at least two different regimens of the same or a different PPI in patients with acute peptic ulcer bleeding, diagnosed endoscopically.

Data collection and analysis: Two reviewers independently selected studies, extracted data and assessed risk of bias. We synthesized data using the Mantel-Haenszel random-effects method and performed multivariate meta-regression with random permutations based on Monte Carlo simulation. We measured heterogeneity with the I² statistic and Cochrane Q test and assessed publication bias with funnel plots and Egger's test. We graded the overall quality of evidence using the GRADE approach.

Main results: Twenty two RCTs were included; risk of bias was high in 17 and unclear in 5. The main analysis included 13 studies (1716 patients) comparing "high" dose regimens (72-hour cumulative dose > 600 mg of intravenous PPI) to other doses; there was no significant heterogeneity for any clinical outcome. We found low quality evidence that did not exclude a potential reduction or increase in mortality, rebleeding, surgical interventions or endoscopic haemostatic treatment (EHT) with "high" dose regimens. For mortality, pooled risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.47 to 1.54); pooled risk difference (RD) was 0 more deaths per 100 patients treated with "high" dose (95% CI from 1 fewer to 2 more deaths per 100 treated). For rebleeding, pooled RR was 1.27 (95% CI 0.96 to 1.67); pooled RD was 2 more rebleeding events per 100 patients treated with "high" dose (95% CI from 0 fewer to 5 more rebleeding events per 100 treated). For surgical interventions, pooled RR was 1.33 (95% CI 0.63 to 2.77); pooled RD was 1 more surgical intervention per 100 patients treated with "high" dose (95% CI from 1 fewer to 2 more surgical interventions per 100 treated). For further EHT, pooled RR was 1.39 (95% CI 0.88 to 2.18), pooled RD was 2 more events per 100 patients treated with "high" dose PPI (95% CI from 1 fewer to 5 more events per 100 treated). We found moderate quality evidence suggesting no important difference between the two regimens with regards to length of hospital stay (mean difference (MD) 0.26 days; 95% CI -0.08 to 0.6 days) or blood transfusion requirements (MD 0.05 units; 95% CI -0.21 to 0.3 units). There was visual and statistical evidence of "inverse" publication bias for mortality (missing small studies with favourable outcomes for "high" dose), but not for any other outcome. The results were similar for all subgroup analyses (according to risk of bias, geographical location, route of administration for non-"high" dose regimens, continuous infusion vs. bolus administration for intravenous non-"high" regimens group), sensitivity analyses (restriction to patients who had EHT for high risk stigmata, use of different dose thresholds for comparative regimens) and post hoc analyses (inclusion of all studies (N = 22) that compared at least two PPI regimens with different cumulative 72 hour doses; restriction of the previous analysis to patients who had EHT for high risk stigmata). Meta-regression analysis did not show any statistically significant associations between treatment effect (for the outcomes of mortality, rebleeding and surgical intervention) and the three study-level factors that were assessed (geographical location (Asia versus not Asia), route of PPI administration (intravenous versus oral), within-study ratio among the 72-hour cumulative doses of the two PPI regimens).

Authors' conclusions: There is insufficient evidence for concluding superiority, inferiority or equivalence of high dose PPI treatment over lower doses in peptic ulcer bleeding.

PubMed Disclaimer

Conflict of interest statement

GI Leontiadis has received speaker honoraria and reimbursement for expenses to attend scientific meetings from AstraZeneca, Sanofi‐Aventis, Janssen‐Cilag and GlaxoSmithKline.

CW Howden has served as a consultant for Takeda, Otsuka and Santarus, and has received speaking honoraria from Takeda, Otsuka and GlaxoSmithKline International. Within the past five years, he has received research support from AstraZeneca for an investigator‐initiated project.

I Neumann, L Letelier, JC Claro, G Rada, Y Yuan and J Martin: no conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 High vs. non‐high (medium or low) dose regimen, outcome: 1.1 Mortality.
5
5
Funnel plot of comparison: 1 High vs. non‐high (medium or low) dose regimen, outcome: 1.2 Rebleeding.
6
6
Funnel plot of comparison: 1 High vs. non‐high (medium or low) dose regimen, outcome: 1.3 Surgery.
7
7
Funnel plot of comparison: 13 Post hoc analysis: studies that compared at least two PPI regimens with different cumulative 72 hour doses, outcome: 13.1 Mortality.
8
8
Funnel plot of comparison: 13 Post hoc analysis: studies that compared at least two PPI regimens with different cumulative 72 hour doses, outcome: 13.2 Rebleeding.
9
9
Funnel plot of comparison: 13 Post hoc analysis: studies that compared at least two PPI regimens with different cumulative 72 hour doses, outcome: 13.3 Surgery.
10
10
Meta‐regression (univariate) for dose ratio and mortality logOR
11
11
Meta‐regression (univariate) for dose ratio and rebleeding logOR
12
12
Post hoc analysis: Meta‐regression (univariate) for dose ratio and rebleeding logOR for all studies that compared at least two doses of PPIs
1.1
1.1. Analysis
Comparison 1 High vs. non‐high (medium or low) dose regimen, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 High vs. non‐high (medium or low) dose regimen, Outcome 2 Rebleeding.
1.3
1.3. Analysis
Comparison 1 High vs. non‐high (medium or low) dose regimen, Outcome 3 Surgery.
1.4
1.4. Analysis
Comparison 1 High vs. non‐high (medium or low) dose regimen, Outcome 4 Further EHT.
1.5
1.5. Analysis
Comparison 1 High vs. non‐high (medium or low) dose regimen, Outcome 5 Length of hospital stay.
1.6
1.6. Analysis
Comparison 1 High vs. non‐high (medium or low) dose regimen, Outcome 6 Blood transfusions.
2.1
2.1. Analysis
Comparison 2 Subgroup analysis: Risk of bias, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 Subgroup analysis: Risk of bias, Outcome 2 Rebleeding.
2.3
2.3. Analysis
Comparison 2 Subgroup analysis: Risk of bias, Outcome 3 Surgery.
2.4
2.4. Analysis
Comparison 2 Subgroup analysis: Risk of bias, Outcome 4 Further EHT.
2.5
2.5. Analysis
Comparison 2 Subgroup analysis: Risk of bias, Outcome 5 LOS.
2.6
2.6. Analysis
Comparison 2 Subgroup analysis: Risk of bias, Outcome 6 Blood transfusions.
3.1
3.1. Analysis
Comparison 3 Subgroup analysis: Geographical location, Outcome 1 Mortality.
3.2
3.2. Analysis
Comparison 3 Subgroup analysis: Geographical location, Outcome 2 Rebleeding.
3.3
3.3. Analysis
Comparison 3 Subgroup analysis: Geographical location, Outcome 3 Surgery.
3.4
3.4. Analysis
Comparison 3 Subgroup analysis: Geographical location, Outcome 4 Further EHT.
3.5
3.5. Analysis
Comparison 3 Subgroup analysis: Geographical location, Outcome 5 LOS.
3.6
3.6. Analysis
Comparison 3 Subgroup analysis: Geographical location, Outcome 6 Blood transfusions.
4.1
4.1. Analysis
Comparison 4 Subgroup analysis: Route of administration in non‐high dose regimen, Outcome 1 Mortality.
4.2
4.2. Analysis
Comparison 4 Subgroup analysis: Route of administration in non‐high dose regimen, Outcome 2 Rebleeding.
4.3
4.3. Analysis
Comparison 4 Subgroup analysis: Route of administration in non‐high dose regimen, Outcome 3 Surgery.
4.4
4.4. Analysis
Comparison 4 Subgroup analysis: Route of administration in non‐high dose regimen, Outcome 4 Further EHT.
4.5
4.5. Analysis
Comparison 4 Subgroup analysis: Route of administration in non‐high dose regimen, Outcome 5 LOS.
4.6
4.6. Analysis
Comparison 4 Subgroup analysis: Route of administration in non‐high dose regimen, Outcome 6 Blood transfusions.
5.1
5.1. Analysis
Comparison 5 Subgroup analysis: IV bolus vs. IV infusion in non‐high dose regimen, Outcome 1 Mortality.
5.2
5.2. Analysis
Comparison 5 Subgroup analysis: IV bolus vs. IV infusion in non‐high dose regimen, Outcome 2 Rebleeding.
5.3
5.3. Analysis
Comparison 5 Subgroup analysis: IV bolus vs. IV infusion in non‐high dose regimen, Outcome 3 Surgery.
5.4
5.4. Analysis
Comparison 5 Subgroup analysis: IV bolus vs. IV infusion in non‐high dose regimen, Outcome 4 Further EHT.
5.5
5.5. Analysis
Comparison 5 Subgroup analysis: IV bolus vs. IV infusion in non‐high dose regimen, Outcome 5 LOS.
5.6
5.6. Analysis
Comparison 5 Subgroup analysis: IV bolus vs. IV infusion in non‐high dose regimen, Outcome 6 Blood transfusions.
6.1
6.1. Analysis
Comparison 6 Subgroup analysis: Type of PPI in high dose regimen, Outcome 1 Mortality.
6.2
6.2. Analysis
Comparison 6 Subgroup analysis: Type of PPI in high dose regimen, Outcome 2 Rebleeding.
6.3
6.3. Analysis
Comparison 6 Subgroup analysis: Type of PPI in high dose regimen, Outcome 3 Surgery.
6.4
6.4. Analysis
Comparison 6 Subgroup analysis: Type of PPI in high dose regimen, Outcome 4 Further EHT.
6.5
6.5. Analysis
Comparison 6 Subgroup analysis: Type of PPI in high dose regimen, Outcome 5 LOS.
6.6
6.6. Analysis
Comparison 6 Subgroup analysis: Type of PPI in high dose regimen, Outcome 6 Blood transfusions.
7.1
7.1. Analysis
Comparison 7 Subgroup analysis: Ulcer site, Outcome 1 Mortality.
7.2
7.2. Analysis
Comparison 7 Subgroup analysis: Ulcer site, Outcome 2 Rebleeding.
7.3
7.3. Analysis
Comparison 7 Subgroup analysis: Ulcer site, Outcome 3 Surgery.
8.1
8.1. Analysis
Comparison 8 Sensitivity analysis: High vs. low dose, Outcome 1 Mortality.
8.2
8.2. Analysis
Comparison 8 Sensitivity analysis: High vs. low dose, Outcome 2 Rebleeding.
8.3
8.3. Analysis
Comparison 8 Sensitivity analysis: High vs. low dose, Outcome 3 Surgery.
9.1
9.1. Analysis
Comparison 9 Sensitivity analysis: High vs. medium dose, Outcome 1 Mortality.
9.2
9.2. Analysis
Comparison 9 Sensitivity analysis: High vs. medium dose, Outcome 2 Rebleeding.
9.3
9.3. Analysis
Comparison 9 Sensitivity analysis: High vs. medium dose, Outcome 3 Surgery.
10.1
10.1. Analysis
Comparison 10 Sensitivity analysis: Medium vs. low dose, Outcome 1 Mortality.
10.2
10.2. Analysis
Comparison 10 Sensitivity analysis: Medium vs. low dose, Outcome 2 Rebleeding.
10.3
10.3. Analysis
Comparison 10 Sensitivity analysis: Medium vs. low dose, Outcome 3 Surgery.
11.1
11.1. Analysis
Comparison 11 Sensitivity analysis: Non‐low (high or medium) dose vs. low dose, Outcome 1 Mortality.
11.2
11.2. Analysis
Comparison 11 Sensitivity analysis: Non‐low (high or medium) dose vs. low dose, Outcome 2 Rebleeding.
11.3
11.3. Analysis
Comparison 11 Sensitivity analysis: Non‐low (high or medium) dose vs. low dose, Outcome 3 Surgery.
12.1
12.1. Analysis
Comparison 12 Sensitivity analysis: High vs. non‐high dose; patients with high risk SRH, Outcome 1 Mortality.
12.2
12.2. Analysis
Comparison 12 Sensitivity analysis: High vs. non‐high dose; patients with high risk SRH, Outcome 2 Rebleeding.
12.3
12.3. Analysis
Comparison 12 Sensitivity analysis: High vs. non‐high dose; patients with high risk SRH, Outcome 3 Surgery.
13.1
13.1. Analysis
Comparison 13 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose, Outcome 1 Mortality.
13.2
13.2. Analysis
Comparison 13 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose, Outcome 2 Rebleeding.
13.3
13.3. Analysis
Comparison 13 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose, Outcome 3 Surgery.
13.4
13.4. Analysis
Comparison 13 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose, Outcome 4 Further EHT.
13.5
13.5. Analysis
Comparison 13 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose, Outcome 5 LOS.
13.6
13.6. Analysis
Comparison 13 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose, Outcome 6 Blood transfusions.
14.1
14.1. Analysis
Comparison 14 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose; high risk SRH, Outcome 1 Mortality.
14.2
14.2. Analysis
Comparison 14 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose; high risk SRH, Outcome 2 Rebleeding.
14.3
14.3. Analysis
Comparison 14 Post hoc analysis: Studies that compared at least two PPI regimens with different 72‐hour cumulative dose; high risk SRH, Outcome 3 Surgery.
15.1
15.1. Analysis
Comparison 15 Post hoc analysis: Comparison of regimens with the same 72‐hour cumulative dose, but different route or frequency, Outcome 1 Rebleeding.
16.1
16.1. Analysis
Comparison 16 Post hoc analysis: IV regimen vs. PO regimen, Outcome 1 Mortality.
16.2
16.2. Analysis
Comparison 16 Post hoc analysis: IV regimen vs. PO regimen, Outcome 2 Rebleeding.
16.3
16.3. Analysis
Comparison 16 Post hoc analysis: IV regimen vs. PO regimen, Outcome 3 Surgery.
16.4
16.4. Analysis
Comparison 16 Post hoc analysis: IV regimen vs. PO regimen, Outcome 4 Further EHT.
16.5
16.5. Analysis
Comparison 16 Post hoc analysis: IV regimen vs. PO regimen, Outcome 5 LOS.
16.6
16.6. Analysis
Comparison 16 Post hoc analysis: IV regimen vs. PO regimen, Outcome 6 Blood transfusions.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Andriulli 2008 {published data only}
    1. Andriulli A, Loperfido S, Focareta R, Leo P, Fornari F, Garripoli A, et al. High‐ versus low‐dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study. American Journal of Gastroenterology 2008;103(12):3011‐8. - PubMed
Bajaj 2007 {published data only}
    1. Bajaj JS, Dua KS, Hanson K, Presberg K. Prospective, randomized trial comparing effect of oral versus intravenous pantoprazole on rebleeding after nonvariceal upper gastrointestinal bleeding: a pilot study. Digestive Diseases and Sciences 2007;52(9):2190‐4. - PubMed
Cheng 2005 {published data only}
    1. Cheng HC, Kao AW, Chuang CH, Sheu BS. The efficacy of high‐ and low‐dose intravenous omeprazole in preventing rebleeding for patients with bleeding peptic ulcers and comorbid illnesses. Digestive Diseases and Sciences 2005;50(7):1194‐201. - PubMed
Cheng 2009 {published data only}
    1. Cheng HC, Chang WL, Yeh YC, Chen WY, Tsai YC, Sheu BS. Seven‐day intravenous low‐dose omeprazole infusion reduces peptic ulcer rebleeding for patients with comorbidities. Gastrointestinal Endoscopy 2009;70(3):433‐9. - PubMed
Choi 2009 {published data only}
    1. Choi KD, Kim N, Jang IJ, Park YS, Cho JY, Kim JR, et al. Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea. Journal of Gastroenterology and Hepatology 2009;24(10):1617‐24. - PubMed
Costamagna 1998 {published data only}
    1. Costamagna G, Mutignani M, Peril V, Colombo GM, Bruni A, Gabbrielli A, et al. Efficacy of i.v. lansoprazole in preventing bleeding relapse in upper gastrointestinal non variceal bleeding. Gastroenterology. 1998; Vol. 114 (Suppl 1):A95.
Dokas 2004 {published data only}
    1. Dokas SM, Lazaraki GI, Kontoninas Z, Kouklakis GS, Adamidou A, Tsiaousi E, et al. Bolus intravenous omeprazole b.i.d. vs. continuous intravenous omeprazole infusion combined with endoscopic hemostasis in the treatment of peptic ulcer bleeding. Preliminary results. Gut. 2004; Vol. 53 (Suppl VI):A290 .
Focareta 2004 {published data only}
    1. Focareta R, Ciarleglio A, Piai G, Levoli F, Forte G. Proton‐pump inhibitor (PPI) and acute peptic ulcer bleeding: effectiveness of oral esomeprazole vs intravenous omeprazole in reducing the risk of recurrent bleeding. Digestive and Liver Disease. 2004; Vol. 36:S250.
Garrido 2008 {published data only}
    1. Garrido A, Giráldez A, Trigo C, Leo E, Guil A, Márquez JL. Intravenous proton‐pump inhibitor for acute peptic ulcer bleeding‐‐is profound acid suppression beneficial to reduce the risk of rebleeding?. Revista Espanola de Enfermedades Digestivas 2008;100(8):466‐9. - PubMed
Hsu 2010 {published data only}
    1. Hsu YC, Perng CL, Yang TH, Wang CS, Hsu WL, Wu HT, et al. A randomized controlled trial comparing two different dosages of infusional pantoprazole in peptic ulcer bleeding. British Journal of Clinical Pharmacology 2010;69(3):245‐51. - PMC - PubMed
Hung 2007 {published data only}
    1. Hung WK, Li VK, Chung CK, Ying MW, Loo CK, Liu CK, et al. Randomized trial comparing pantoprazole infusion, bolus and no treatment on gastric pH and recurrent bleeding in peptic ulcers. Australian and New Zealand Journal of Surgery 2007;77(8):677‐81. - PubMed
Jang 2006 {published data only}
    1. Jang JY, Dong SH, Jung JH, Chae MJ, Kim NH, Lee SK, et al. High‐dose oral proton pump inhibitor is as effective as intravenous administration in the aspect of increasing intragastric pH and reducing rebleeding after endoscopic treatment of bleeding peptic ulcers. Gastroenterology. 2006; Vol. 130 (4 suppl 2):A467.
Lin 1997 {published data only}
    1. Lin HJ, Lo WC, Perng CL, Wang K, Lee FY. Can optimal acid suppression prevent rebleeding in peptic ulcer patients with a non‐bleeding visible vessel: a preliminary report of a randomized comparative study. Hepatogastroenterology 1997;44:1495‐9. - PubMed
Lin 2006 {published data only}
    1. Lin HJ, Lo WC, Cheng YC, Perng CL. Role of intravenous omeprazole in patients with high‐risk peptic ulcer bleeding after successful endoscopic epinephrine injection: a prospective randomized comparative trial. American Journal of Gastroenterology 2006;101(3):500‐5. - PubMed
Mesihovic 2009 {published data only}
    1. Mesihovic R, Vanis N, Mehmedovic A, Gornjakovic S, Gribajcevic M. Proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding. Medicinski Arhiv 2009;63(6):323‐7. - PubMed
Oh 2007 {published data only}
    1. Oh JH, Choi MG, Dong MS, Park JM, Paik CN, Cho YK, et al. Low‐dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients. Journal of Gastroenterology and Hepatology 2007;22(9):1429‐34. - PubMed
Schonekas 1999 {published data only}
    1. Schonekas H, Ahrens H, Pannewick U, Ell C, Koop H, Petritsch W, et al. Comparison of two doses of intravenous pantoprazole in peptic ulcer bleeding. Gastroenterology. 1999; Vol. 116 (4 Part 2):A305.
Sha 2001 {published data only}
    1. Sha W, Li Y, Nie Y, Wu W, Li Q, Zhou Y, et al. Effect of endoscopic therapy and omeprazole injection on patients with active bleeding peptic ulcer. Chinese Journal of Digestive Endoscopy 2001;18(2):87‐9.
Tsai 2009 {published data only}
    1. Tsai JJ, Hsu YC, Perng CL, Lin HJ. Oral or intravenous proton pump inhibitor in patients with peptic ulcer bleeding after successful endoscopic epinephrine injection. British Journal of Clinical Pharmacology 2009;67(3):326‐32. - PMC - PubMed
Udd 2001 {published data only}
    1. Udd M, Miettinen P, Palmu A, Heikkinen M, Janatuinen E, Pasanen P, et al. Regular‐dose versus high‐dose omeprazole in peptic ulcer bleeding: a prospective randomized double‐blind study. Scandinavian Journal of Gastroenterology 2001;36(12):1332‐8. - PubMed
Yilmaz 2006 {published data only}
    1. Yilmaz S, Bayan K, Tüzün Y, Dursun M, Canoruç F. A head to head comparison of oral vs intravenous omeprazole for patients with bleeding peptic ulcers with a clean base, flat spots and adherent clots. World Journal of Gastroenterology 2006;12(48):7837‐43. - PMC - PubMed
Yüksel 2008 {published data only}
    1. Yüksel I, Ataseven H, Köklü S, Ertuğrul I, Başar O, Odemiş B, et al. Intermittent versus continuous pantoprazole infusion in peptic ulcer bleeding: a prospective randomized study. Digestion 2008;78(1):39‐43. - PubMed

References to studies excluded from this review

Adamek 1993 {published data only}
    1. Adamek RJ, Wegener M. Combined intravenous and oral omeprazole/amoxicillin therapy in patients with Helicobacter pylori‐positive acute peptic ulcer bleeding. American Journal of Gastroenterology 1993;88(11):1980. - PubMed
Andrews 2005 {published data only}
    1. Andrews CN, Levy A, Fishman M, Hahn M, Atkinson K, Kwan P, et al. Intravenous proton pump inhibitors before endoscopy in bleeding peptic ulcer with high‐risk stigmata: a multicentre comparative study. Canadian Journal of Gastroenterology 2005;19(11):667‐71. - PubMed
Arasaradnam 2003 {published data only}
    1. Arasaradnam RP, Riley SA. Optimal medical therapy with proton pump inhibitor infusion to prevent recurrent ulcer hemorrhage in patients with adherent clots. Gastroenterology 2003;125(1):276. - PubMed
Arnesen 2007 {published data only}
    1. Arnesen Ø, Riis JS. Platelet inhibition and gastric problems [Blodplatehemming og mageproblemer]. Tidsskrift for Den Norske Laegeforening 2007;127(1):64. - PubMed
Bai 1995 {published data only}
    1. Bai G, Hu FL, Lu DH, Qin J. Efficacy of intravenous administration of omeprazole in the treatment of upper gastrointestinal hemorrhage caused by peptic ulcer and acute gastric mucosal lesion. Chinese Journal of Clinical Pharmacology 1995;11:206‐9.
Barkun 2004 {published data only}
    1. Barkun AN, Herba K, Adam V, Kennedy W, Fallone CA, Bardou M. The cost‐effectiveness of high‐dose oral proton pump inhibition after endoscopy in the acute treatment of peptic ulcer bleeding. Alimentary Pharmacology and Therapeutics 2004;20(2):195‐202. - PubMed
Bazzoli 2001 {published data only}
    1. Bazzoli F. Key points from the revised Maastricht Consensus Report: the impact on general practice. European Journal of Gastroenterology & Hepatology 2001;13(Suppl 2):S3‐7. - PubMed
Berstad 1997 {published data only}
    1. Berstad A. Does profound acid inhibition improve haemostasis in peptic ulcer bleeding? [comment]. Scandinavian Journal of Gastroenterology 1997;32(4):396‐8. - PubMed
Bolten 2003 {published data only}
    1. Bolten WW. In high risk patients cyclooxygenase inhibitor plus proton pump inhibitor [Bei hochrisikopatienten coxibe plus protonenpumpenhemmer]. MMW Fortschritte der Medizin 2003;145(5):9. - PubMed
Bour 1993 {published data only}
    1. Bour B, Pariente EA, Hamelin B, Garcia E. Orally administered omeprazole versus injection therapy in the prevention of rebleeding from peptic ulcer with visible vessel. A multicenter randomized study. Gastroenterologie Clinique et Biologique 1993;17(5):329‐33. - PubMed
Calvet 1998 {published data only}
    1. Calvet X, Garcia N, Campo R, Brullet E, Comet R, Navarro M. Two‐day quadruple therapy for cure of Helicobacter pylori infection: A comparative, randomized trial. American Journal of Gastroenterology 1998;93(6):932‐4. - PubMed
Chahin 2006 {published data only}
    1. Chahin NJ, Meli M, Zaccà F. Endoscopic injection plus continuous intravenous pantoprazole vs endoscopic injection plus continuous intravenous omeprazole for the treatment of upper non variceal bleeding. Canadian Journal of Gastroenterology 2006;20(Suppl A):112.
Chan 2008 {published data only}
    1. Chan FK. Proton‐pump inhibitors in peptic ulcer disease. Lancet 2008;372(9645):1198‐200. - PubMed
Chen 1996 {published data only}
    1. Chen CY, Chen CY, Chang TT, Lin XZ. Intravenous omeprazole plus antibiotics in Helicobacter‐related peptic ulcer patients with major stigmata of recent hemorrhage ‐ a preliminary report of a randomized controlled trial. Gut. 1996; Vol. 39, issue Suppl 3:A141.
Cherniakevich 2002 {published data only}
    1. Cherniakevich SA, Babkova IV, Mikhalev AI. Results of pre‐ and postoperative treatment of complicated duodenal ulcers with proton pump inhibitors [Rezul'taty lecheniia ingibitorami protonnoi pompy oslozhnennykh duodenal'nykh iazv do i posle operativnykh vmeshatel'stv]. Klinicheska Meditsina 2002;80(9):52‐4. - PubMed
Chilovi 2003 {published data only}
    1. Chilovi F, Piazzi L, Zancanella L, Guelmi A, Grasso T, Fede F, et al. Intravenous omeprazole and pantoprazole after endoscopic treatment of bleeding peptic ulcers. Gastrointestinal Endoscopy 2003;57(5):AB150.
Choi 2006 {published data only}
    1. Choi MG, Oh JH, Park JM, Paik CN, Lee JW, Cho YK, et al. The effect of various doses of pantoprazole on the intragastric acidity for preventing ulcer rebleeding after endoscopic therapy in Korean patients. Gastroenterology 2006;130(4 Suppl 2):A‐466.
Chua 1996 {published data only}
    1. Chua RT, Lin HJ, Wang K, Perng CL, Lo WC, Lee CH, et al. Intravenous omeprazole prevents rebleeding in peptic ulcer patients with a non‐bleeding visible vessel: a preliminary report of a randomized controlled study. Zhonghua Yi Xue Za Zhi 1996;57(2):139‐45. - PubMed
de‐Muckadell 1996 {published data only}
    1. de‐Muckadell OBS, Havelund T, Harling H, Boesby S, Snel P, Vreeburg EM, et al. The effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers: a randomized double‐blind placebo‐controlled multicentre study. Netherlands Journal of Medicine. 1996; Vol. 48:A3‐A4. - PubMed
Heldwein 1992 {published data only}
    1. Heldwein W, Schreiner J, Müller‐Lissner S. No ulcer hemorrhage without acid? [Ohne saure keine ulkusblutung?]. Zeitschrift fur Gastroenterologie 1992;30(11):820‐1. - PubMed
Kamada 1996a {published data only}
    1. Kamada T, Sugiyama M, Takemoto T, Ogawa N, Namiki M, Kimura K, et al. A late phase II evaluation of lansoprazole (AG‐1749) injection on upper gastrointestinal bleeding: a randomized dose finding study. Rinsho Iyaku 1996;12:2901‐25.
Kamada 1996b {published data only}
    1. Kamada T, Sugiyama M, Takemoto T, Ogawa N, Namiki M, Kimura K, et al. An early phase II study of lansoprazole (AG‐1749) injection on upper gastrointestinal bleeding: A randomized pilot study on clinical dosages. Rinsho Iyaku 1996;12:2885‐900.
Kovacs 1999 {published data only}
    1. Kovacs TO, Campbell D, Richter J, Haber M, Jennings DE, Rose P. Double‐blind comparison of lansoprazole 15 mg, lansoprazole 30 mg and placebo as maintenance therapy in patients with healed duodenal ulcers resistant to H2‐receptor antagonists. Alimentary Pharmacology and Therapeutics 1999;13(7):959‐67. - PubMed
Krizman 1997 {published data only}
    1. Krizman I, Ribnikar M, Kozjek F, Primozic S. Comparative amoxicillin ‐ Azithromycin treatment of Helicobacter pylori positive patients with bleeding duodenal ulcer. Acta Pharmaceutica 1997;47:183‐8.
Labenz 1997 {published data only}
    1. Labenz J, Beker JA, Dekkers CPM, Farley A, Klor H‐U, Jonsson A. Doubling the omeprazole dose (40 mg b.d. vs. 20 mg b.d.) in dual therapy with amoxicillin increases the cure rate of Helicobacter pylori infection in duodenal ulcer patients. Alimentary Pharmacology and Therapeutics 1997;11(3):515‐22. - PubMed
Laine 2008 {published data only}
    1. Laine L, Shah A, Bemanian S. Intragastric pH with oral vs intravenous bolus plus infusion proton‐pump inhibitor therapy in patients with bleeding ulcers. Gastroenterology 2008;134(7):1836‐41. - PubMed
Langman 1990 {published data only}
    1. Langman MJ. Problems in assessing pharmacologic treatment of acute upper gastrointestinal bleeding. Hepato‐Gastroenterology 1990;37(Suppl 1):29‐30. - PubMed
Lesur 2005 {published data only}
    1. Lesur G, Bour B. Proton pump inhibitors and upper gastrointestinal bleeding [Inhibiteurs de la pompe a protons et hemorragies digestives hautes]. Gastroenterologie Clinique et Biologique 2005;29(2):137‐9. - PubMed
Libby 2000 {published data only}
    1. Libby ED. Omeprazole to prevent recurrent bleeding after endoscopic treatment of ulcers. New England Journal of Medicine 2000;343(5):358‐9. - PubMed
Lin 1995 {published data only}
    1. Lin HJ, Wang K, Chua RT, Perng CL, Lee SD. Intravenous omeprazole prevents rebleeding in peptic ulcer patients with a non‐bleeding visible vessel ‐ A preliminary report of a randomized controlled trial (abstract). Endoscopy. 1995; Vol. 27:S5. - PubMed
Lin 2009 {published data only}
    1. Lin HJ. Proton pump inhibitors after endoscopy in peptic ulcer bleeding. American Journal of Gastroenterology 2009;104(6):1595. - PubMed
Miyoshi 1995 {published data only}
    1. Miyoshi AA. A dose finding study of omeprazole injection in upper gastrointestinal bleeding by a double‐blind method. Yakuri to Chiryo 1995;23:S2137‐52.
Mönkemüller 2002 {published data only}
    1. Mönkemüller KE, Eloubeidi MA. Bleeding peptic ulcers: what's new?. Gastrointestinal Endoscopy 2002;56(1):153‐7. - PubMed
Murthy 2007 {published data only}
    1. Murthy S, Keyvani L, Leeson S, Targownik LE. Intravenous versus high‐dose oral proton pump inhibitor therapy after endoscopic hemostasis of high‐risk lesions in patients with acute nonvariceal upper gastrointestinal bleeding. Digestive Diseases and Sciences 2007;52(7):1685‐90. - PubMed
Nehme 2001 {published data only}
    1. Nehme O, Barkin JS. Recurrent ulcer bleeding: is intravenous omeprazole the solution?. American Journal of Gastroenterology 2001;96(2):594‐5. - PubMed
Nishioka 1996 {published data only}
    1. Nishioka S, Ogoshi K, Ogawa N. Clinical study of lansoprazole (AG‐1749) injection on upper gastrointestinal bleeding: hemostatic effect of lansoprazole injection and preventive effect of lansoprazole capsules on re‐bleeding. Rinsho Iyaku 1996;12:2927‐52.
O'Leary 1991 {published data only}
    1. O'Leary MJ, Park GR. Intravenous omeprazole in upper gastrointestinal haemorrhage in critically ill patients. Digestion 1991;48(1):59‐60. - PubMed
Peitz 2004 {published data only}
    1. Peitz U, Leodolter A, Wex T, Schutze D, Wolle K, Welte T, et al. Diagnostics of Helicobacter pylori infection in patients with peptic ulcer bleeding. Zeitschrift fur Gastroenterologie 2004;42(2):141‐6. - PubMed
Peura 2005 {published data only}
    1. Peura DA. Clinical implications of immediate‐release PPI therapy in the management of GERD and upper GI bleeding. Introduction. Alimentary Pharmacology and Therapeutics 2005;22(Suppl 3):1. - PubMed
Ponce Romero 2003 {published data only}
    1. Ponce Romero M, Berenguer Lapuerta J. Current indications for proton pump inhibitors [Indicaciones actuales de los inhibidores de la bomba de protones]. Revista Clinica Espanola 2003;203(3):136‐8. - PubMed
Pulanic 2000 {published data only}
    1. Pulanic R, Brkic T, Opacic M, Katicic M, Duvnjak M, Babic Z, et al. Efficacy of different doses of intravenous pantoprazole application with regard to endoscopic sclerotherapy in prevention of rebleeding from gastroduodenal ulcers type forrest IIa, b. Endoscopy. 2000; Vol. 32:E30.
Rösch 2007 {published data only}
    1. Rösch T. Highlights of United European Gastroenterology Week 2006. Endoscopy 2007;39(3):238‐46. - PubMed
Salas 2002 {published data only}
    1. Salas M, Ward A, Caro J. Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials. BMC Gastroenterology 2002;2:17. - PMC - PubMed
Savides 2001 {published data only}
    1. Savides TJ, Pratha V. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Gastrointestinal Endoscopy 2001;54(1):130‐2. - PubMed
Scheurlen 2000 {published data only}
    1. Scheurlen M. Peptic ulcer hemorrhage: i.v. antacid prevents recurrence [Ulkusblutung: saurehemmer i.v. schutzt vor rezidiv]. MMW Fortschritte der Medizin 2000;142(45):30. - PubMed
Seppälä 1995 {published data only}
    1. Seppälä K, Haapiainen R, Sipponen P, Halttunen J, Färkkilä M, Sarna S, et al. Two weeks antimicrobials and omeprazole therapy is sufficient to cure Helibacter pylori positive bleeding peptic ulcer ‐ a randomized trial. Gut 1995;37(Suppl 2):A193.
Sonnenberg 1999 {published data only}
    1. Sonnenberg A, Olson CA, Zhang J. The effect of antibiotic therapy on bleeding from duodenal ulcer. American Journal of Gastroenterology 1999;94(4):950‐4. - PubMed
Spiegel 2006 {published data only}
    1. Spiegel BM, Dulai GS, Lim BS, Mann N, Kanwal F, Gralnek IM. The cost‐effectiveness and budget impact of intravenous versus oral proton pump inhibitors in peptic ulcer hemorrhage. Clinical Gastroenterology and Hepatology 2006;4(8):988‐97. - PubMed
Tseng 1999 {published data only}
    1. Tseng GY, Lin HJ, Lin HY, Perng CL, Lee FY, Lo WC, et al. The influence of intravenous omeprazole on intragastric pH and outcomes in patients with peptic ulcer bleeding after successful endoscopic therapy‐‐a prospective randomized comparative trial. Hepato‐Gastroenterology 1999;46(28):2183‐8. - PubMed
Udd 1999 {published data only}
    1. Udd M, Miettinen P, Janatuinen E, Heikkinen M, Tarvainen R, Pasanen P, et al. Regular vs. high dose of omeprazole for peptic ulcer bleeding ‐ prospective randomised double blind study. Annales Chirurgiae et Gynaecologiae 1999;88:169.
Vcev 1996 {published data only}
    1. Vcev A, Horvat D, Rubinic M, Stimac D, Vceva A, Uravic M, et al. Eradication of Helicobacter pylori reduces the possibility of rebleeding in duodenal ulcer disease. Acta Facultatis Medicae Fluminensis 1996;21:59‐65.
Wu 2000 {published data only}
    1. Wu XP, He JR, Wang CL, Ling QH. Effect of pantoprazole on non‐variceal bleeding. Bulletin of Hunan Medical University 2000;25:361‐2. - PubMed
Xu 1993 {published data only}
    1. Xu P, Zhou CX, Chen QF. Efficacy of omeprazole intravenously on peptic ulcer with hemorrhage of 90 patients. Chinese Journal of Practical Internal Medicine 1993;13:421.
Zhonglin 2002 {published data only}
    1. Zhonglin Y, Sanren L, Huiji W. Effectiveness and safety of pantoprazole i.v. and omeprazole i.v. in the treatment of patients with peptic ulcer bleeding. Journal of Gastroenterology and Hepatology 2002;17:A257.
Zimmerli 2003 {published data only}
    1. Zimmerli L. Regular‐dose versus high‐dose omeprazole in peptic ulcer bleeding: a prospective randomized double‐blind study. Schweizerische Rundschau fur Medizin Praxis 2003;92:205.

Additional references

Barkun 2010a
    1. Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Annals of Internal Medicine 2010;152(2):101‐11. - PubMed
Barkun 2010b
    1. Barkun A, Leontiadis G. Systematic review of the symptom burden, quality of life impairment and costs associated with peptic ulcer disease. American Journal of Medicine 2010;123(4):358‐66. - PubMed
Calvet 2005
    1. Calvet X, Gomollon F. What is potent acid inhibition, and how can it be achieved?. Drugs 2005;65(Suppl 1):13‐23. - PubMed
Chen 2012
    1. Chen J, Yuan YC, Leontiadis GI, Howden CW. Recent safety concerns with proton pump inhibitors. Journal of Clinical Gastroenterology 2012;46(2):93‐114. - PubMed
de Leest 2004
    1. Leest H, Dieten H, Tulder M, Lems WF, Dijkmans BA, Boers M. Costs of treating bleeding and perforated peptic ulcers in The Netherlands. Journal of Rheumatology 2004;31:788‐91. - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315:629‐34. - PMC - PubMed
Gralnek 2008
    1. Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. New England Journal of Medicine 2008;359:928‐37. - PubMed
Green 1978
    1. Green FJ, Kaplan MM, Curtis LE, Levine PH. Effects of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor to prolonged gastroduodenal mucosal haemorrhage. Gastroenterology 1978;74(1):38‐43. - PubMed
Higgins 2010
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Howden 2010
    1. Howden CW. Editorial: PPIs and clopidogrel: the band plays on............. American Journal of Gastroenterology 2010;105(11):2438‐9. - PubMed
Jensen 2006
    1. Jensen DM, Pace SC, Soffer E, Comer GM, 315 Study Group. Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: A U.S. multicenter randomized, double‐blind study. American Journal of Gastroenterology 2006;101(9):1991‐9. - PubMed
Klok 2003
    1. Klok RM, Postma MJ, Hout BA, Brouwers JR. Meta‐analysis: comparing the efficacy of proton pump inhibitors in short‐term use. Alimentary Pharmacology and Therapeutics 2003;17:1237‐45. - PubMed
Kwok 2012
    1. Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta‐analysis. American Journal of Gastroenterology 2012;107(7):1011‐9. - PubMed
Laine 2012
    1. Laine L, Jensen DM. Management of patients with ulcer bleeding. American Journal of Gastroenterology 2012;107(3):345‐60. - PubMed
Lassen 2006
    1. Lassen A, Hallas J, Schaffalitzky de Muckadell OB. Complicated and uncomplicated peptic ulcers in a Danish county 1993‐2002: a population‐based cohort study. American Journal of Gastroenterology 2006;101:945‐53. - PubMed
Leontiadis 2006a
    1. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD002094.pub3] - DOI - PubMed
Leontiadis 2006b
    1. Leontiadis GI, Howden CW. To establish the efficacy of PPI therapy for ulcer bleeding in the United States, do we need more patients or more PPI?. American Journal of Gastroenterology 2006;101(9):2000‐2. - PubMed
Leontiadis 2007a
    1. Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW, et al. Systematic reviews of the clinical effectiveness and cost‐effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technology Assessment 2007;11(51):1‐164. - PubMed
Leontiadis 2007b
    1. Leontiadis GI, Howden CW. Pharmacologic treatment of peptic ulcer bleeding. Current Treatment Options in Gastroenterology 2007;10(2):134‐42. - PubMed
Leontiadis 2009
    1. Leontiadis GI, Howden CW. The role of proton pump inhibitors in the management of upper gastrointestinal bleeding. Gastroenterology Clinics of North America 2009;38(2):199‐213. - PubMed
Leontiadis 2010
    1. Leontiadis GI, Howden CW. Proton pump inhibitor dose for ulcer bleeding: is less really more?. Archives of Internal Medicine 2010;170(18):1697‐8. - PubMed
Leontiadis 2011
    1. Leontiadis GI, Yuan Y, Howden CW. The interaction between proton pump inhibitors and clopidogrel and upper gastrointestinal bleeding. Gastrointestinal Endoscopy Clinics of North America 2011;21(4):637‐56. - PubMed
Leontiadis 2012
    1. Leontiadis GI, Miller MA, Howden CW. How much do PPIs contribute to C. difficile infections?. American Journal of Gastroenterology 2012;107(7):1020‐1. - PubMed
Levine 2004
    1. Levine JE, Leontiadis GI, Sharma VK, Howden CW. Meta‐analysis: the efficacy of intravenous H2‐receptor antagonists in bleeding peptic ulcer. Alimentary Pharmacology and Therapeutics 2002;16(6):1137‐42. - PubMed
Moayyedi 2012
    1. Moayyedi P, Leontiadis GI. The risks of PPI therapy. Nature Reviews. Gastroenterology & Hepatology 2012;9(3):132‐9. - PubMed
Ngamruengphong 2011
    1. Ngamruengphong S, Leontiadis GI, Radhi S, Dentino A, Nugent K. Proton pump inhibitors and risk of fracture: a systematic review and meta‐analysis of observational studies. American Journal of Gastroenterology 2011;106(7):1209‐18. - PubMed
NICE 2012
    1. National Institute for Health and Clinical Excellence. CG141 Acute upper GI bleeding: NICE guideline. http://guidance.nice.org.uk/CG141/NICEGuidance/pdf (accessed 17 October 2012).
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12. - PubMed
Sreedharan 2010
    1. Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010, Issue 7. [DOI: 10.1002/14651858.CD005415.pub3] - DOI - PubMed
Stata 2005 [Computer program]
    1. StataCorp LP. Intercooled STATA for Windows. Version 8.2. College Station, USA: StataCorp LP, 2005.
StatsDirect 2008 [Computer program]
    1. StatsDirect Ltd. StatsDirect version 2.7.8. England: StatsDirect Ltd, 2008.
Targownik 2006
    1. Targownik LE, Nabalamba A. Trends in management and outcomes of acute nonvariceal upper gastrointestinal bleeding: 1993‐2003. Clinical Gastroenterology and Hepatology 2006;4(12):1459‐66. - PubMed
Vakil 2009
    1. Vakil N. Acid inhibition and infections outside the gastrointestinal tract. American Journal of Gastroenterology 2009;104(Suppl 2):17‐20. - PubMed
van Boxel 2010
    1. Boxel OS, Oijen MG, Hagenaars MP, Smout AJ, Siersema PD. Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. American Journal of Gastroenterology 2010;105(11):2430‐6. - PubMed
van Leerdam 2003
    1. Leerdam ME, Vreeburg EM, Rauws EA, Geraedts AA, Tijssen JG, Reitsma JB, et al. Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. American Journal of Gastroenterology 2003;98(7):1494‐9. - PubMed
Wang 2010
    1. Wang CH, Ma MH, Chou HC, Yen ZS, Yang CW, Fang CC, et al. High‐dose vs non‐high‐dose proton pump inhibitors after endoscopic treatment in patients with bleeding peptic ulcer: a systematic review and meta‐analysis of randomized controlled trials. Archives of Internal Medicine 2010;170(9):751‐8. - PubMed
Wu 2010
    1. Wu LC, Cao YF, Huang JH, Liao C, Gao F. High‐dose vs low‐dose proton pump inhibitors for upper gastrointestinal bleeding: a meta‐analysis. World Journal of Gastroenterology 2010;16(20):2558‐65. - PMC - PubMed
Yacyshyn 2002
    1. Yacyshyn BR, Thomson AB. The clinical importance of proton pump inhibitor pharmacokinetics. Digestion 2002;66:67‐78. - PubMed

MeSH terms

Substances