Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Ian M. Gralnek; Jean-Marc Dumonceau; Ernst J. Kuipers; Angel Lanas; David S. Sanders; Matthew Kurien; Gianluca Rotondano; Tomas Hucl; Mario Dinis-Ribeiro; Riccardo Marmo; Istvan Racz; Alberto Arezzo; Ralf-Thorsten Hoffmann; Gilles Lesur; Roberto de Franchis; Lars Aabakken; Andrew Veitch; Franco Radaelli; Paulo Salgueiro; Ricardo Cardoso; Luís Maia; Angelo Zullo; Livio Cipolletta; Cesare Hassan

doi:10.1055/s-0034-1393172

Endoscopy, Table of Contents

Endoscopy 2015; 47(10): a1-a46
DOI: 10.1055/s-0034-1393172

Guideline

Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Ian M. Gralnek

¹Institute of Gastroenterology and Liver Diseases, Ha'Emek Medical Center, Afula, Israel

²Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa, Israel

,

Jean-Marc Dumonceau

³Gedyt Endoscopy Center, Buenos Aires, Argentina

,

Ernst J. Kuipers

⁴Departments of Internal Medicine and Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands

,

Angel Lanas

⁵University of Zaragoza, Aragon Health Research Institute (IIS Aragon), CIBERehd, Spain

,

David S. Sanders

⁶Department of Gastroenterology, Sheffield Teaching Hospitals, United Kingdom

,

Matthew Kurien

⁶Department of Gastroenterology, Sheffield Teaching Hospitals, United Kingdom

,

Gianluca Rotondano

⁷Division of Gastroenterology and Digestive Endoscopy, Maresca Hospital, Torre del Greco, Italy

,

Tomas Hucl

⁸Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

,

Mario Dinis-Ribeiro

⁹Department of Gastroenterology, IPO Porto, Portugal and CINTESIS, Porto Faculty of Medicine, Portgal

,

Riccardo Marmo

¹⁰Division of Gastroenterology, Hospital Curto, Polla, Italy

,

Istvan Racz

¹¹First Department of Internal Medicine and Gastroenterology, Petz Aladar, Hospital, Gyor, Hungary

,

Alberto Arezzo

¹²Department of Surgical Sciences, University of Torino, Torino, Italy

,

Ralf-Thorsten Hoffmann

¹³Institute and Polyclinic for Diagnostic Radiology, University Hospital Dresden-TU, Dresden, Germany

,

Gilles Lesur

¹⁴Department of Gastroenterology, Ambroise Paré Hospital, Boulogne, France

,

Roberto de Franchis

¹⁵Department of Biomedical and Clinical Sciences, University of Milan, Gastroenterology Unit, Luigi Sacco University Hospital, Milan, Italy

,

Lars Aabakken

¹⁶Department of Medical Gastroenterology, Rikshospitalet University Hospital, Oslo, Norway

,

Andrew Veitch

¹⁷Department of Gastroenterology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom

,

Franco Radaelli

¹⁸Department of Gastroenterology, Valduce Hospital, Como, Italy

,

Paulo Salgueiro

¹⁹Department of Gastroenterology, Centro Hospitalar do Porto, Portugal

,

Ricardo Cardoso

²⁰Department of Gastroenterology, Centro Hospitalar e Universitário de Coimbra, Portugal

,

Luís Maia

¹⁹Department of Gastroenterology, Centro Hospitalar do Porto, Portugal

,

Angelo Zullo

²¹Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy

,

Livio Cipolletta

²²Gastroenterology and Endoscopy Department, Antonio Cardarelli Hospital, Naples, Italy

,

Cesare Hassan

²³Digestive Endoscopy Unit, Catholic University, Rome, Italy

› Author Affiliations

Abstract

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH).

Main Recommendations

MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence).

MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence).

MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 – 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence).

MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence).

MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence).

MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 – 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence).

MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence).

MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence).

MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence).

MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence).

MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence).

MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence).

MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence).

MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence).

MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).

Full Text

References

References
1 van Leerdam ME. Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol 2008; 22: 209-224
2 Hearnshaw SA, Logan RF, Lowe D et al. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut 2011; 60: 1327-1335
3 Guyatt GH, Oxman AD, Vist GE et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924-926
4 Dumonceau JM, Hassan C, Riphaus A et al. European Society of Gastroinestinal Endoscopy (ESGE) guideline development policy. Endoscopy 2012; 44: 626-629
5 Baradarian R, Ramdhaney S, Chapalamadugu R et al. Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol 2004; 99: 619-622
6 Kwan I, Bunn F, Chinnock P et al. Timing and volume of fluid administration for patients with bleeding. Cochrane Database Syst Rev 2014; 3: CD002245
7 Spahn DR, Bouillon B, Cerny V et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care 2013; 17: R76
8 Roberts I, Alderson P, Bunn F et al. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2004; 4: CD000567
9 Myburgh JA, Finfer S, Bellomo R et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367: 1901-1911
10 Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med 2008; 36: 2667-2674
11 Restellini S, Kherad O, Jairath V et al. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther 2013; 37: 316-322
12 Villanueva C, Colomo A, Bosch A et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368: 11-21
13 Jairath V, Kahan BC, Stanworth SJ et al. Prevalence, management, and outcomes of patients with coagulopathy after acute nonvariceal upper gastrointestinal bleeding in the United Kingdom. Transfusion 2013; 53: 1069-1076
14 Shingina A, Barkun AN, Razzaghi A et al. Systematic review: the presenting international normalized ratio (INR) as a predictor of outcome in patients with upper nonvariceal gastrointestinal bleeding. Aliment Pharmacol Ther 2011; 33: 1010-1018
15 Karam O, Tucci M, Combescure C et al. Plasma transfusion strategies for critically ill patients. Cochrane Database Syst Rev 2013; 12: CD010654
16 Razzaghi A, Barkun AN. Platelet transfusion threshold in patients with upper gastrointestinal bleeding: a systematic review. J Clin Gastroenterol 2012; 46: 482-486
17 Rockall TA, Logan RF, Devlin HB et al. Risk assessment after acute upper gastrointestinal haemorrhage. Gut 1996; 38: 316-321
18 Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet 2000; 356: 1318-1321
19 de Groot NL, Bosman JH, Siersema PD et al. Prediction scores in gastrointestinal bleeding: a systematic review and quantitative appraisal. Endoscopy 2012; 44: 731-739
20 Lee JG, Turnipseed S, Romano PS et al. Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial. Gastrointest Endosc 1999; 50: 755-761
21 Cipolletta L, Bianco MA, Rotondano G et al. Outpatient management for low-risk nonvariceal upper GI bleeding: a randomized controlled trial. Gastrointest Endosc 2002; 55: 1-5
22 Brullet E, Campo R, Calvet X et al. A randomized study of the safety of outpatient care for patients with bleeding peptic ulcer treated by endoscopic injection. Gastrointest Endosc 2004; 60: 15-21
23 Longstreth GF, Feitelberg SP. Outpatient care of selected patients with acute non-variceal upper gastrointestinal haemorrhage. Lancet 1995; 345: 108-111
24 Longstreth GF, Feitelberg SP. Successful outpatient management of acute upper gastrointestinal hemorrhage: use of practice guidelines in a large patient series. Gastrointest Endosc 1998; 47: 219-222
25 Rockall TA, Logan RF, Devlin HB et al. Selection of patients for early discharge or outpatient care after acute upper gastrointestinal haemorrhage. national audit of acute upper gastrointestinal haemorrhage. Lancet 1996; 347: 1138-1140
26 Lai KC, Hui WM, Wong BC et al. A retrospective and prospective study on the safety of discharging selected patients with duodenal ulcer bleeding on the same day as endoscopy. Gastrointest Endosc 1997; 45: 26-30
27 Cebollero-Santamaria F, Smith J, Gioe S et al. Selective outpatient management of upper gastrointestinal bleeding in the elderly. Am J Gastroenterol 1999; 94: 1242-1247
28 Gralnek IM, Dulai GS. Incremental value of upper endoscopy for triage of patients with acute non-variceal upper GI hemorrhage. Gastrointest Endosc 2004; 60: 9-14
29 Guerrouij M, Uppal CS, Alklabi A et al. The clinical impact of bleeding during oral anticoagulant therapy: assessment of morbidity, mortality and post-bleed anticoagulant management. J Thromb Thrombolysis 2011; 31: 419-423
30 Holbrook A, Schulman S, Witt DM et al. Evidence-based management of anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e152S-184S
31 Irwin ST, Ferguson R, Weilert F et al. Supratherapeutic anticoagulation at presentation is associated with reduced mortality in nonvariceal upper gastrointestinal hemorrhage. Endosc Int Open 2014; 2: E148-E152 [Epub 2014 Jul 10]
32 Tran HA, Chunilal SD, Harper PL et al. An update of consensus guidelines for warfarin reversal. Med J Aust 2013; 198: 198-199
33 Choudari CP, Rajgopal C, Palmer KR. Acute gastrointestinal hemorrhage in anticoagulated patients: diagnoses and response to endoscopic treatment. Gut 1994; 35: 464-466
34 Radaelli F, Paggi S, Terruzzi V et al. Management of warfarin-associated coagulopathy in patients with acute gastrointestinal bleeding: a cross-sectional physician survey of current practice. Dig Liver Dis 2011; 43: 444-447
35 Patriquin C, Crowther M. Treatment of warfarin-associated coagulopathy with vitamin K. Expert Rev Hematol 2011; 4: 657-665
36 Baron TH, Kamath PS, McBane RD. New anticoagulant and antiplatelet agents: a primer for the gastroenterologist. Clin Gastroenterol Hepatol 2014; 12: 187-195
37 Leissinger CA, Blatt PM, Hoots WK et al. Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol 2008; 83: 137-143
38 Karaca MA, Erbil B, Ozmen MM. Use and effectiveness of prothrombin complex concentrates vs. fresh frozen plasma in gastrointestinal hemorrhage due to warfarin usage in the ED. Am J Emerg Med 2014; 32: 660-664
39 Dentali F, Marchesi C, Pierfranceschi MG et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost 2011; 106: 429-438
40 Hickey M, Gatien M, Taljaard M et al. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation 2013; 128: 360-364
41 Chai-Adisaksopha C, Crowther M, Isayama T et al. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124: 2450-2458
42 Holster IL, Valkhoff VE, Kuipers EJ et al. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 2013; 145: 105-112
43 Ruff CT, Guigliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet 2014; 383: 955-962
44 Lu G, DeGuzman FR, Hollenbach SJ et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013; 19: 446-451
45 Ansell JE, Bakhru SH, Laulicht BE et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014; 371: 2141-2142
46 Pollack Jr CV, Reilly PA, Eikelboob J et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373: 511-520
47 Abraham NS, Castillo DL. Novel anticoagulants: bleeding risk and management strategies. Curr Opin Gastroenterol 2013; 29: 676-683
48 Desai J, Kolb JM, Weitz JI et al. Gastrointestinal bleeding with the new oral anticoagulants – defining the issues and the management strategies. Thromb Haemost 2013; 110: 205-212
49 Makris M, Van Veen JJ, Tait CR et al. British Committee for Standards in Haematology. Guideline on the management of bleeding in patients on antithrombotic agents. Br J Haematol 2013; 160: 35-46
50 Siegal DM, Cuker A. Reversal of novel oral anticoagulants in patients with major bleeding. J Thromb Thrombolysis 2013; 35: 391-398
51 Fawole A, Daw HA, Crowther MA. Practical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixaban. Clev Clin J Med 2013; 80: 443-451
52 Boustiere C, Veitch A, Vanbiervliet G et al. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2011; 43: 445-461
53 Sung JJY, Lau JYW, Ching JYL et al. Continuation of low dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med 2010; 152: 1-9
54 Derogar M, Sandblom G, Lundell L et al. Discontinuation of low dose aspirin therapy after peptic ulcer bleeding increases risk of death and acute cardiovascular events. Clin Gastroenterol Hepatol 2013; 11: 38-42
55 Liu C-P, Chen W-C, Lai K-H et al. Esomeprazole alone compared with esomeprazole plus aspirin for the treatment of aspirin-related peptic ulcers. Am J Gastroenterol 2012; 107: 1022-1029
56 Ng FH, Wong BCY, Wong SY et al. Clopidogrel plus omeprazole compared with aspirin plus omeprazole for aspirin-induced symptomatic peptic ulcers/erosions with low to moderate bleeding/re-bleeding risk – a single-blind, randomized controlled study. Aliment Pharmacol Ther 2004; 19: 359-365
57 Sreedharan A, Martin J, Leontiadis GI et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev 2010; 7: CD005415
58 Sabah AlS, Barkun AN, Herba K et al. Cost-effectiveness of proton-pump inhibition before endoscopy in upper gastrointestinal bleeding. Clin Gastroenterol Hepatol 2008; 6: 418-425
59 Tsoi KKF, Lau JYW, Sung JJY. Cost-effectiveness analysis of high-dose omeprazole infusion before endoscopy for patients with upper-GI bleeding. Gastrointest Endosc 2008; 67: 1056-1063
60 Shakur H, Roberts I. CRASH-2 trial collaborators et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet 2010; 376: 23-32
61 Gluud LL, Klingenberg SL, Langholz E. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2012; 1: CD006640
62 Raptis S, Dollinger HC, von Berger L et al. Effects of somatostatin on gastric secretion and gastrin release in man. Digestion 1975; 13: 15-26
63 Hearnshaw SA, Logan RF, Lowe D et al. Use of endoscopy for management of acute upper gastrointestinal bleeding in the UK: results of a nationwide audit. Gut 2010; 59: 1022-1029
64 Enestvedt BK, Gralnek IM, Mattek N et al. An evaluation of endoscopic indications and findings related to non-variceal upper-GI hemorrhage in a large multicenter consortium. Gastrointest Endosc 2008; 67: 422-429
65 Barkun AN, Bardou M, Martel M et al. Prokinetics in acute upper GI bleeding: a meta-analysis. Gastrointest Endosc 2010; 72: 1138-1145
66 Szary NM, Gupta R, Choudhary A et al. Erythromycin prior to endoscopy in acute upper gastrointestinal bleeding: a meta-analysis. Scand J Gastroenterol 2011; 46: 920-924
67 Bai Y, Guo JF, Li ZS. Meta-analysis: erythromycin before endoscopy for acute upper gastrointestinal bleeding. Aliment Pharmacol Ther 2011; 34: 166-171
68 Theivanayagam S, Lim RG, Cobell WJ et al. Administration of erythromycin before endoscopy in upper gastrointestinal bleeding: a meta-analysis of randomized controlled trials. Saudi J Gastroenterol 2013; 19: 205-210
69 Winstead NS, Wilcox CM. Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost–effectiveness analysis. Aliment Pharmacol Ther 2007; 26: 1371-1377
70 Srygley FD, Gerardo CJ, Tran T et al. Does this patient have a severe upper gastrointestinal bleed?. JAMA 2012; 307: 1072-1079
71 Aljebreen AM, Fallone CA, Barkun AN. Nasogastric aspirate predicts high-risk endoscopic lesions in patients with acute upper GI bleeding. Gastrointest Endosc 2004; 59: 172-178
72 Pateron D, Vicaut E, Debuc E et al. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. Ann Emerg Med 2011; 57: 582-589
73 Huang ES, Karsan S, Kanwal F et al. Impact of nasogastric lavage on outcomes in acute GI bleeding. Gastrointest Endosc 2011; 74: 971-980
74 Singer AJ, Richman PB, Kowalska A et al. Comparison of patient and practitioner assessments of pain from commonly performed emergency department procedures. Ann Emerg Med 1999; 33: 652-658
75 Koch DG, Arguedas MR, Fallon MB. Risk of aspiration pneumonia in suspected variceal hemorrhage: the value of prophylactic endotracheal intubation prior to endoscopy. Dig Dis Sci 2007; 52: 2225-2228
76 Rehman A, Iscimen R, Yilmaz M et al. Prophylactic endotracheal intubation in critically ill patients undergoing endoscopy for upper GI hemorrhage. Gastrointest Endosc 2009; 69: 55-59
77 Rudolph SJ, Landsverk BK, Freeman ML. Endotracheal intubation for airway protection during endoscopy for severe upper GI hemorrhage. Gastrointest Endosc 2003; 57: 58-61
78 Kanwal F, Barkun A, Gralnek IM et al. Measuring quality of care in patients with nonvariceal upper gastrointestinal hemorrhage: development of an explicit quality indicator set. Am J Gastroenterol 2010; 105: 1710-1718
79 Lanas A, Aabakken L, Fonseca J et al. Variability in the management of nonvariceal upper gastrointestinal bleeding in Europe: an observational study. Adv Ther 2012; 29: 1026-1036
80 Spiegel BM, Vakil NB, Ofman JJ. Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review. Arch Intern Med 2001; 161: 1393-1404
81 Tsoi KKF, Ma TKW, Sung JJY. Endoscopy for upper gastrointestinal bleeding: how urgent is it?. Nat Rev Gastroenterol Hepatol 2009; 6: 463-469
82 Wysocki JD, Srivastav S, Winstead NS. A nationwide analysis of risk factors for mortality and time to endoscopy in upper gastrointestinal haemorrhage. Aliment Pharmacol Ther 2012; 36: 30-36
83 Lin HJ, Wang K, Perng CL et al. Early or delayed endoscopy for patients with peptic ulcer bleeding. A prospective randomized study. J Clin Gastroenterol 1996; 22: 267-271
84 Lim L, Ho K, Chan Y et al. Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. Endoscopy 2011; 43: 300-306
85 Bjorkman DJ, Zaman A, Fennerty MB et al. Urgent vs. elective endoscopy for acute non-variceal upper-GI bleeding: an effectiveness study. Gastrointest Endosc 2004; 60: 1-8
86 Stanley AJ, Ashley D, Dalton HR et al. Outpatient management of patients with low-risk upper-gastrointestinal haemorrhage: multicentre validation and prospective evaluation. Lancet 2009; 373: 42-47
87 McLaughlin C, Vine L, Chapman L et al. The management of low-risk primary upper gastrointestinal haemorrhage in the community. Eur J Gastroenterol Hepatol 2012; 24: 288-293
88 Girardin M, Bertolini D, Ditisheim S et al. Use of Glasgow-Blatchford bleeding score reduces hospital stay duration and costs for patients with low-risk upper GI bleeding. Endosc Int Open 2014; 2: E74-E79 Epub 2014 May 7
89 Laursen SB, Dalton HR, Murray IA et al. Performance of new thresholds of the Glasgow Blatchford score in managing patients with upper gastrointestinal bleeding. Clin Gastroenterol Hepatol 2015; 13: 115-121
90 Rubin M, Hussain SA, Shalomov A et al. Live view video capsule endoscopy enables risk stratification of patients with acute upper GI bleeding in the emergency room: a pilot study. Dig Dis Sci 2011; 56: 786-791
91 Chandran S, Testro A, Urquhart P et al. Risk stratification of upper GI bleeding with an esophageal capsule. Gastrointest Endosc 2013; 77: 891-898
92 Gralnek IM, Ching JYL, Maza I et al. Capsule endoscopy in acute upper gastrointestinal hemorrhage: a prospective cohort study. Endoscopy 2013; 45: 12-19
93 Meltzer AC, Ali MA, Kresiberg RB et al. Video capsule endoscopy in the emergency department: a prospective study of acute upper gastrointestinal hemorrhage. Ann Emerg Med 2013; 61: 438-443
94 Meltzer AC, Pinchbeck C, Burnett S et al. Emergency physicians accurately interpret video capsule endoscopy findings in suspected upper gastrointestinal hemorrhage: a video survey. Acad Emerg Med 2013; 20: 711-715
95 Meltzer AC, Ward MJ, Gralnek IM et al. The cost–effectiveness analysis of video capsule endoscopy compared to other strategies to manage acute upper gastrointestinal hemorrhage in the ED. Am J Emerg Med 2014; 32: 823-832
96 Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet 1974; 2: 394-397
97 Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med 2008; 359: 928-937
98 Barkun AN, Bardou M, Kuipers EJ et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010; 152: 101-113
99 Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol 2012; 107: 345-360
100 Chung IK, Kim EJ, Lee MS et al. Endoscopic factors predisposing to rebleeding following endoscopic hemostasis in bleeding peptic ulcers. Endoscopy 2001; 33: 969-975
101 Guglielmi A, Ruzzenente A, Sandri M et al. Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer. Endoscopy 2002; 34: 778-786
102 Zaragoza AM, Tenías JM, Llorente MJ et al. Prognostic factors in gastrointestinal bleeding due to peptic ulcer: construction of a predictive model. J Clin Gastroenterol 2008; 42: 786-790
103 Elmunzer BJ, Young SD, Inadomi JM et al. Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers. Am J Gastroenterol 2008; 103: 2625-2632
104 Marmo R, Del Piano M, Rotondano G et al. Mortality from nonulcer bleeding is similar to that of ulcer bleeding in high-risk patients with nonvariceal hemorrhage: a prospective database study in Italy. Gastrointest Endosc 2012; 75: 263-272
105 Bratanic A, Puljiz Z, Ljubicicz N et al. Predictive factors of rebleeding and mortality following endoscopic hemostasis in bleeding peptic ulcers. Hepatogastroenterology 2013; 60: 112-117
106 Sung JJ, Barkun A, Kuipers EJ et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med 2009; 50: 455-464
107 de Groot NL, van Oijen MG, Kessels K et al. Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified?. Endoscopy 2014; 46: 46-52
108 Lau JY, Sung JJ, Chan AC et al. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc 1997; 46: 33-36
109 Mondardini A, Barletti C, Rocca G et al. Non-variceal upper gastrointestinal bleeding and Forrest’s classification: diagnostic agreement between endoscopists from the same area. Endoscopy 1998; 30: 508-512
110 Lin HJ, Perng CL, Lee FY et al. Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. Gut 1994; 35: 1389-1393
111 Cheng CL, Lin CH, Kuo CJ et al. Predictors of rebleeding and mortality in patients with high-risk bleeding peptic ulcers. Dig Dis Sci 2010; 55: 2577-2583
112 Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol 2009; 7: 33-47
113 Sung J, Chan F, Lau J et al. The effect of endoscopic therapy in patients receiving omeprazole for bleeding ulcers with nonbleeding visible vessels or adherent clots: a randomized comparison. Ann Intern Med 2003; 139: 237-243
114 Andriulli A, Annese V, Caruso N et al. Proton-pump inhibitors and outcome of endoscopic hemostasis in bleeding peptic ulcers: a series of meta-analyses. Am J Gastroenterol 2005; 100: 207-219
115 Lin JH, Wang K, Perng CL et al. Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation. Gastrointest Endosc 1996; 43: 470-473
116 Jensen DM, Kovacs TO, Jutabha R et al. Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots. Gastroenterology 2002; 123: 407-413
117 Bleau BL, Gostout CJ, Sherman KE et al. Recurrent bleeding from peptic ulcer associated with adherent clot: a randomized study comparing endoscopic treatment with medical therapy. Gastrointest Endosc 2002; 56: 1-6
118 Kahi CJ, Jensen DM, Sung JJY et al. Endoscopic therapy versus medical therapy for bleeding peptic ulcer with adherent clot: a meta-analysis. Gastroenterology 2005; 129: 855-862
119 Wong RC, Chak A, Kobayashi K et al. Role of Doppler US in acute peptic ulcer hemorrhage: can it predict failure of endoscopic therapy?. Gastrointest Endosc 2000; 52: 315-121
120 Kohler B, Maier M, Benz C et al. Acute ulcer bleeding. A prospective randomized trial to compare Doppler and Forrest classifications in endoscopic diagnosis and therapy. Dig Dis Sci 1997; 42: 1370-1374
121 Fullarton GM, Murray WR. Prediction of rebleeding in peptic ulcers by visual stigmata and endoscopic Doppler ultrasound criteria. Endoscopy 1990; 22: 68-71
122 Kohler B, Riemann JF. Endoscopic injection therapy of Forrest II and III gastroduodenal ulcers guided by endoscopic Doppler ultrasound. Endoscopy 1993; 25: 219-223
123 van Leerdam ME, Rauws EA, Geraedts AA et al. The role of endoscopic Doppler US in patients with peptic ulcer bleeding. Gastrointest Endosc 2003; 58: 677-684
124 Chen VK, Wong RC. Endoscopic doppler ultrasound versus endoscopic stigmata-directed management of acute peptic ulcer hemorrhage: a multimodel cost analysis. Dig Dis Sci 2007; 52: 149-160
125 Cipolletta L, Bianco MA, Salerno R et al. Improved characterization of visible vessels in bleeding ulcers by using magnification endoscopy: results of a pilot study. Gastrointest Endosc 2010; 72: 413-418
126 Barkun AN, Martel M, Toubouti Y et al. Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses. Gastrointest Endosc 2009; 69: 786-799
127 ASGE Technology Committee. Conway JD, Adler DG et al. Endoscopic hemostatic devices. Gastrointest Endosc 2009; 69: 987-996
128 Laine L. Therapeutic endoscopy and bleeding ulcers. Bipolar/multipolar electrocoagulation. Gastrointest Endosc 1990; 36: S38-S41
129 Ginsberg GG, Barkun AN, Bosco JJ et al. The argon plasma coagulator. Gastrointest Endosc 2002; 55: 807-810
130 Watson JP, Bennett MK, Griffin SM et al. The tissue effect of argon plasma coagulation on esophageal and gastric mucosa. Gastrointest Endosc 2000; 52: 342-345
131 Raju GS, Gajula L. Endoclips for GI endoscopy. Gastrointest Endosc 2004; 59: 267-279
132 Chuttani R, Barkun A, Carpenter S et al. Endoscopic clip application devices. Gastrointest Endosc 2006; 63: 746-750
133 Kirschniak A, Kratt T, Stüker D et al. A new endoscopic over-the-scope clip system for treatment of lesions and bleeding in the GI tract: first clinical experiences. Gastrointest Endosc 2007; 66: 162-167
134 Kirschniak A, Subotova N, Zieker D et al. The over-the-scope clip (OTSC) for the treatment of gastrointestinal bleeding, perforations, and fistulas. Surg Endosc 2011; 25: 2901-2905
135 Gottlieb KT, Banerjee S, Barth BA. ASGE Technology Committee et al. Endoscopic closure devices. Gastrointest Endosc 2012; 76: 244-251
136 Barkun AN, Moosavi S, Martel M. Topical hemostatic agents: a systematic review with particular emphasis on endoscopic application in GI bleeding. Gastrointest Endosc 2013; 77: 692-700
137 Sung JJ, Tsoi KK, Lai LH et al. Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis. Gut 2007; 56: 1364-1373
138 Calvet X, Vergara M, Brullet E et al. Addition of a second endoscopic treatment following epinephrine injection improves outcome in high-risk bleeding ulcers. Gastroenterology 2004; 126: 441-450
139 Marmo R, Rotondano G, Piscopo R et al. Dual therapy versus monotherapy in the endoscopic treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials. Am J Gastroenterol 2007; 102: 279-289
140 Vergara M, Bennett C, Calvet X et al. Epinephrine injection versus epinephrine injection and a second endoscopic method in high risk bleeding ulcers. Cochrane Database Syst Rev 2014; 10: CD005584
141 Hwang JH, Fisher DA, Ben-Menachem T et al. Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc 2012; 75: 1132-1138
142 Yuan Y, Wang C, Hunt RH. Endoscopic clipping for acute nonvariceal upper-GI bleeding: a meta-analysis and critical appraisal of randomized controlled trials. Gastrointest Endosc 2008; 68: 339-351
143 Arima S, Sakata Y, Ogata S et al. Evaluation of hemostasis with soft coagulation using endoscopic hemostatic forceps in comparison with metallic hemoclips for bleeding gastric ulcers: a prospective, randomized trial. J Gastroenterol 2010; 45: 501-505
144 Kataoka M, Kawai T, Hayama Y et al. Comparison of hemostasis using bipolar hemostatic forceps with hemostasis by endoscopic hemoclipping for nonvariceal upper gastrointestinal bleeding in a prospective non-randomized trial. Surg Endosc 2013; 27: 3035-3038
145 Sung JJ, Chan FK, Chen M et al. Asia-Pacific Working Group consensus on non-variceal upper gastrointestinal bleeding. Gut 2011; 60: 1170-1177
146 Wong Kee Song LM, Banerjee S, Barth BA et al. Emerging technologies for endoscopic hemostasis. Gastrointest Endosc 2012; 75: 933-937
147 Manta R, Galloro G, Mangiavillano B et al. Over-the-scope clip (OTSC) represents an effective endoscopic treatment for acute GI bleeding after failure of conventional techniques. Surg Endosc 2013; 27: 3162-3164
148 Giday SA, Kim Y, Krishnamurty DM et al. Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model. Endoscopy 2011; 43: 296-269
149 Chen YI, Barkun AN, Soulellis C et al. Use of the endoscopically applied hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary experience. Gastrointest Endosc 2012; 75: 1278-1281
150 Leblanc S, Vienne A, Dhooge M et al. Early experience with a novel hemostatic powder used to treat upper GI bleeding related to malignancies or after therapeutic interventions. Gastrointest Endosc 2013; 78: 169-175
151 Holster IL, Kuipers EJ, Tjwa ET. Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy. Endoscopy 2013; 45: 63-66
152 Yau AH, Ou G, Galorport C et al. Safety and efficacy of Hemospray in upper gastrointestinal bleeding. Can J Gastroenterol Hepatol 2014; 28: 72-76
153 Sung JJ, Luo D, Wu JC et al. Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy 2011; 43: 291-295
154 Smith LA, Stanley AJ, Bergman JJ et al. Hemospray application in nonvariceal upper gastrointestinal bleeding: results of the survey to evaluate the application of hemospray in the luminal tract. J Clin Gastroenterol 2014; 48: 89-92
155 Barkun A, Sabbah S, Enns R et al. The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic hemostasis and proton pump inhibition are associated with improved outcomes in a real-life setting. Am J Gastroenterol 2004; 99: 1238-1246
156 Nahon S, Nouel O, Hagège H et al. Favorable prognosis of upper-gastrointestinal bleeding in 1041 older patients: results of a prospective multicenter study. Clin Gastroenterol Hepatol 2008; 6: 886-892
157 Loperfido S, Baldo V, Piovesana E et al. Changing trends in acute upper-GI bleeding: a population-based study. Gastrointest Endosc 2009; 70: 212-224
158 Guntipalli P, Chason R, Elliott A et al. Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome. Dig Dis Sci 2014; 59: 2997-3003
159 Wang WH, Huang JQ, Zheng GF et al. Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis. World J Gastroenterol 2005; 11: 4067-4077
160 Gralnek IM, Dulai GS, Fennerty MB et al. Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials. Clin Gastroenterol Hepatol 2006; 4: 1452-1458
161 Ljubičić N, Budimir I, Pavić T et al. Mortality in high-risk patients with bleeding Mallory–Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study. Scand J Gastroenterol 2014; 49: 458-464
162 Bharucha AE, Gostout CJ, Balm RK. Clinical and endoscopic risk factors in the Mallory-Weiss syndrome. Am J Gastroenterol 1997; 92: 805-808
163 Kortas DY, Haas LS, Simpson WG et al. Mallory–Weiss tear: predisposing factors and predictors of a complicated course. Am J Gastroenterol 2001; 96: 2863-2865
164 Chung IK, Kim EJ, Hwang KY et al. Evaluation of endoscopic hemostasis in upper gastrointestinal bleeding related to Mallory–Weiss syndrome. Endoscopy 2002; 34: 474-479
165 Kim JW, Kim HS, Byun JW et al. Predictive factors of recurrent bleeding in Mallory–Weiss syndrome. Korean J Gastroenterol 2005; 46: 447-454
166 Fujisawa N, Inamori M, Sekino Y et al. Risk factors for mortality in patients with Mallory–Weiss syndrome. Hepatogastroenterology 2011; 58: 417-420
167 Huang SP, Wang HP, Lee YC et al. Endoscopic hemoclip placement and epinephrine injection for Mallory-Weiss syndrome with active bleeding. Gastrointest Endosc 2002; 55: 842-846
168 Park CH, Min SW, Sohn YH et al. A prospective, randomized trial of endoscopic band ligation vs. epinephrine injection for actively bleeding Mallory–Weiss syndrome. Gastrointest Endosc 2004; 60: 22-27
169 Cho YS, Chae HS, Kim HK et al. Endoscopic band ligation and endoscopic hemoclip placement for patients with Mallory–Weiss syndrome and active bleeding. World J Gastroenterol 2008; 14: 2080-2084
170 Lecleire S, Antonietti M, Iwanicki-Caron I et al. Endoscopic band ligation could decrease recurrent bleeding in Mallory–Weiss syndrome as compared to haemostasis by hemoclips plus epinephrine. Aliment Pharmacol Ther 2009; 30: 399-405
171 Lara LF, Sreenarasimhaiah J, Tang SJ et al. Dieulafoy lesions of the GI tract: localization and therapeutic outcomes. Dig Dis Sci 2010; 55: 3436-3441
172 Chung IK, Kim EJ, Lee MS et al. Bleeding Dieulafoy’s lesions and the choice of endoscopic method: comparing the hemostatic efficacy of mechanical and injection methods. Gastrointest Endosc 2000; 52: 721-724
173 Kasapidis P, Georgopoulos P, Delis V et al. Endoscopic management and long-term follow-up of Dieulafoy’s lesions in the upper GI tract. Gastrointest Endosc 2002; 55: 527-531
174 Cheng CL, Liu NJ, Lee CS et al. Endoscopic management of Dieulafoy lesions in acute nonvariceal upper gastrointestinal bleeding. Dig Dis Sci 2004; 49: 1139-1144
175 Park CH, Sohn YH, Lee WS et al. The usefulness of endoscopic hemoclipping for bleeding Dieulafoy lesions. Endoscopy 2003; 35: 388-392
176 Katsinelos P, Paroutoglou G, Mimidis K et al. Endoscopic treatment and follow-up of gastrointestinal Dieulafoy’s lesions. World J Gastroenterol 2005; 11: 6022-6026
177 Iacopini F, Petruzziello L, Marchese M et al. Hemostasis of Dieulafoy’s lesions by argon plasma coagulation (with video). Gastrointest Endosc 2007; 66: 20-26
178 Alis H, Oner OZ, Kalayci MU et al. Is endoscopic band ligation superior to injection therapy for Dieulafoy lesion?. Surg Endosc 2009; 23: 1465-1469
179 Sone Y, Kumada T, Toyoda H et al. Endoscopic management and follow up of Dieulafoy’s lesion in the upper gastrointestinal tract. Endoscopy 2005; 37: 449-453
180 Lim W, Kim TO, Park SB et al. Endoscopic treatment of Dieulafoy lesions and risk factors for rebleeding. Korean J Intern Med 2009; 24: 318-322
181 Durham JD, Kumpe DA, Rothbarth LJ et al. Dieulafoy disease: arteriographic findings and treatment. Radiology 1990; 174: 937-941
182 Alshumrani G, Almuaikeel M. Angiographic findings and endovascular embolization in Dieulafoy disease: a case report and literature review. Diagn Interv Radiol 2006; 12: 151-154
183 Jackson CS, Gerson LB. Management of gastrointestinal angiodysplastic lesions (GIADs): a systematic review and meta-analysis. Am J Gastroenterol 2014; 109: 474-483
184 Swanson E, Mahgoub A, MacDonald R et al. Medical and endoscopic therapies for angiodysplasia and gastric antral vascular ectasia: a systematic review. Clin Gastroenterol Hepatol 2014; 12: 571-582
185 Heller SJ, Tokar JL, Nguyen MT et al. Management of bleeding GI tumors. Gastrointest Endosc 2010; 72: 817-824
186 Sheibani S, Kim JJ, Chen B et al. Natural history of acute upper GI bleeding due to tumours: short-term success and long-term recurrence with or without endoscopic therapy. Aliment Pharmacol Ther 2013; 38: 144-150
187 Kim YI, Choi IJ, Cho SJ et al. Outcome of endoscopic therapy for cancer bleeding in patients with unresectable gastric cancer. J Gastroenterol Hepatol 2013; 28: 1489-1495
188 Koh KH, Kim K, Kwon DH et al. The successful endoscopic hemostasis factors in bleeding from advanced gastric cancer. Gastric Cancer 2013; 16: 397-403
189 Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev 2006; 1: CD002094
190 Leontiadis G, Martin J, Sharma V et al. T1942 Proton pump inhibitor (PPI) treatment for peptic ulcer (PU) bleeding: an updated Cochrane meta-analysis of randomized controlled trials (RCTs) [abstract]. Gastroenterology 2009;
191 Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med 2014; 174: 1755-1762
192 Javid G, Zargar SA, U-Saif R et al. Comparison of p. o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer. J Gastroenterol Hepatol 2009; 24: 1236-1243
193 Sung JJ, Suen BY, Wu JC et al. Effects of intravenous and oral esomeprazole in the prevention of recurrent bleeding from peptic ulcers after endoscopic therapy. Am J Gastroenterol 2014; 109: 1005-1010
194 Lau JYW, Sung JJY, Lam YH et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcer. N Engl J Med 1999; 340: 751-756
195 Wong TCF, Wong TT, Chiu PWY et al. A comparison of angiographic embolization with surgery after failed endoscopic hemostasis to bleeding peptic ulcers. Gastrointest Endosc 2011; 73: 900-908
196 Kyaw M, Tse Y, Ang D et al. Embolization versus surgery for peptic ulcer bleeding after failed endoscopic hemostasis: a meta-analysis. Endos Int Open 2014; 2: E6-E14
197 Beggs AD, Dilworth MP, Powell SL et al. A systematic review of transarterial embolization versus emergency surgery in treatment of major nonvariceal upper gastrointestinal bleeding. Clin Exp Gastroenterol 2014; 7: 93-104
198 Sulz M, Frei R, Meyenberger C et al. Routine use of Hemospray for gastrointestinal bleeding: prospective two-center experience in Switzerland. Endoscopy 2014; 46: 619-624
199 El OualiS, Barkun AN, Wyse J et al. Is routine second-look endoscopy effective after endoscopic hemostasis in acute peptic ulcer bleeding? A meta-analysis. Gastrointest Endosc 2012; 76: 283-292
200 Imperiale TF, Kong N. Second look endoscopy for bleeding peptic ulcer disease: a decision and cost-effectiveness analysis. J Clin Gastroenterol 2012; 46: e71-e75
201 Holster IL, Kuipers EJ. Management of acute nonvariceal upper gastrointestinal bleeding: current policies and future perspectives. World J Gastroenterol 2012; 18: 1202-1207
202 Sbrozzi-Vanni A, Zullo A, Di Giulio E et al. Low prevalence of idiopathic peptic ulcer disease: an Italian endoscopic survey. Dig Liver Dis 2010; 42: 773-776
203 Gisbert JP, Khorrami S, Carballo F et al. Meta-analysis: Helicobacter pylori eradication therapy vs. anti-secretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Aliment Pharmacol Ther 2004; 19: 617-629
204 Gisbert JP, Calvet X, Cosme A et al. Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding. Am J Gastroenterol 2012; 107: 1197-1204
205 Gisbert JP, Abraira V. Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis. Am J Gastroenterol 2006; 101: 848-863
206 Sánchez-Delgado J, Gené E, Suárez D et al. Has H. pylori prevalence in bleeding peptic ulcer been underestimated? A meta-regression. Am J Gastroenterol 2011; 106: 398-405
207 Witt DM, Delate T, Garcia DA et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med 2012; 172: 1484-1491
208 Lee JK, Kang HW, Kim SG et al. Risks related with withholding and resuming anticoagulation in patients with non-variceal upper gastrointestinal bleeding while on warfarin therapy. Int J Clin Pract 2012; 66: 64-68
209 Qureshi W, Mittal C, Patsias I et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. Am J Cardiol 2014; 113: 662-668
210 Douketis JD, Spyropoulos AC, Spencer FA et al. Perioperative management of antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 Suppl e326S-e350S
211 Sibon I, Orgogozo JM. Antiplatelet drug discontinuation is a risk factor for ischemic stroke. Neurology 2004; 62: 1187-1189
212 Biondi-Zoccai GG, Lotrionte M, Agostoni P et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J 2006; 27: 2667-2674
213 Garcia-Rodriguez LA, Cea-Soriano L, Martin-Merino E et al. Discontinuation of low dose aspirin and risk of myocardial infarction: case–control study in UK primary care. BMJ 2011; 343: d4094
214 Cea Soriano L, Bueno H, Lanas A et al. Cardiovascular and upper gastrointestinal bleeding consequences of low dose acetylsalicylic acid discontinuation. Thromb Haemost 2013; 110: 1298-1304
215 King III SB, Smith Jr SC, Hirshfeld Jr JW et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol 2008; 51: 172-209
216 Anderson JL, Adams CD, Antman EM et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: 179-347
217 Garcia-Rodriguez LA, Lin KJ, Hernandez-Diaz S et al. Risk of upper gastrointestinal bleeding with low dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation 2011; 123: 1108-1115
218 Lanas A, Garcia-Rodriguez LA, Arroyo MT et al. Effect of anti-secretory drugs and nitrates on the risk of ulcer bleeding associated with non-steroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 2007; 102: 507-515
219 Bhatt DL, Scheiman J, Abraham NS et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008; 118: 1894-1909
220 Kwok CS, Nijar RS, Loke YK. Effects of proton pump inhibitors on adverse gastrointestinal events in patients receiving clopidogrel: a systematic review and meta-analysis. Drug Saf 2011; 34: 47-57
221 Gilard M, Arnaud B, Cornily JC et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 2008; 51: 256-260
222 Cuisset T, Frere C, Quilici J et al. Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose: the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study. J Am Coll Cardiol 2009; 54: 1149-1153
223 Siller-Matula JM, Spiel AO, Lang IM et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009; 157: 148-145
224 O’Donoghue ML, Braunwald E, Antman EM et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009; 374: 989-997
225 Chen J, Chen SY, Lian JJ et al. Pharmacodynamic impacts of proton pump inhibitors on the efficacy of clopidogrel in vivo – a systematic review. Clin Cardiol 2013; 36: 184-189
226 Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther 2010; 31: 810-823
227 Siller-Matula JM, Jilma B, Schror K et al. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J Thromb Haemost 2010; 8: 2624-2641
228 Cardoso RN, Benjo AM, DiNicolantonio JJ et al. Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis. Open Heart 2015; 2: e000248

References for Appendices
229 Longstreth GF, Feitelberg SP. Outpatient care of selected patients with acute non-variceal upper gastrointestinal haemorrhage. Lancet 1995; 345: 108-111
230 Longstreth GF, Feitelberg SP. Successful outpatient management of acute upper gastrointestinal hemorrhage: use of practice guidelines in a large patient series. Gastrointest Endosc 1998; 47: 219-222
231 Cebollero-Santamaria F, Smith J, Gioe S et al. Selective outpatient management of upper gastrointestinal bleeding in the elderly. Am J Gastroenterol 1999; 94: 1242-1247
232 Brullet E, Campo R, Calvet X et al. A randomized study of the safety of outpatient care for patients with bleeding peptic ulcer treated by endoscopic injection. Gastrointest Endosc 2004; 60: 15-21
233 Lai KC, Hui WM, Wong BC et al. A retrospective and prospective study on the safety of discharging selected patients with duodenal ulcer bleeding on the same day as endoscopy. Gastrointest Endosc 1997; 45: 26-30
234 Lee JG, Turnipseed S, Romano PS et al. Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial. Gastrointest Endosc 1999; 50: 755-761
235 Gralnek IM, Dulai GS. Incremental value of upper endoscopy for triage of patients with acute non-variceal upper GI hemorrhage. Gastrointest Endosc 2004; 60: 9-14
236 Cipolletta L, Bianco MA, Rotondano G et al. Outpatient management for low-risk nonvariceal upper GI bleeding: a randomized controlled trial. Gastrointest Endosc 2002; 55: 1-5
237 Sreedharan A, Martin J, Leontiadis GI et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev 2010; 7: CD005415
238 Lau JY, Leung WK, Wu JC et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007; 356: 1631-40
239 Liu N, Liu L, Zhang HH et al. Effect of intravenous proton pump inhibitor requirements and timing of endoscopy of peptic ulcer bleeding. J Gastroenterol Hepatol 2012; 27: 1473-79
240 Barkun AN, Bardou M, Kuipers EJ et al. International consensus recommendations on the management of patients with non-variceal upper gastrointestinal bleeding. Ann Intern Med 2010; 152: 101-113
241 Tsoi KKF, Lau JYW, Sung JJY. Cost-effectiveness analysis of high-dose omeprazole infusion before endoscopy for patients with upper GI bleeding. Gastrointest Endosc 2008; 67: 1056-1063
242 Barkun AN. Should every patient with suspected upper GI bleeding receive a proton pump inhibitor while awaiting endoscopy?. Gastrointest Endosc 2008; 67: 1064-1066
243 Rácz I, Szalai M, Dancs N et al. Pantoprazole before endoscopy in patients with gastroduodenal ulcer bleeding: Does the duration of infusion and ulcer location influence the effects?. Gastroenterol Res Pract 2012; Article ID561207
244 Lanas A. Update on non variceal gastrointestinal bleeding. Gastroenterol Hepatol 2013; 36: 57-65
245 Sung JJ, Chan FK, Chen M et al. Asia-Pacific Working consensus on non-variceal upper gastrointestinal bleeding. Gut 2011; 60: 1170-1177
246 Al-Sabah S, Barkun AN, Herba K et al. Cost-effectiveness of proton pump inhibition before endoscopy in upper gastrointestinal bleeding. Clin Gastroenterol Hepatol 2008; 6: 418-425
247 Ghassemi KA, Kovacs TOG, Jensen DM. Gastric acid inhibition in the treatment of peptic ulcer haemorrhage. Curr Gastroenterol Rep 2009; 11: 462-469
248 Laursen SB, Jorgensen HS, Schaffalitzky de Muckadell OB. Management of bleeding gastroduodenal ulcers. Dan Med J 2012; 59: C4473
249 Lin HJ. Role of proton pump inhibitors in the management of peptic ulcer bleeding. World J Gastrointest Pharmacol Ther 2010; 1: 51-53
250 Gluud LL, Klingenberg SL, Langholz E. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2012; 1: CD006640
251 Magnusson I, Ihre T, Johansson C et al. Randomized double blind trial of somatostatin in the treatment of massive upper gastrointestinal hemorrhage. Gut 1985; 26: 221-226
252 Choi CW, Kang DH, Kim HW et al. Somatostatin adjunctive therapy for non-variceal upper gastrointestinal rebleeding after endoscopic therapy. World J Gastroenterol 2011; 17: 3441-3447
253 Avgerinos A, Sgouros S, Viazis N et al. Somatostatin inhibits gastric acid secretion more effectively than pantoprazole in patients with peptic ulcer bleeding: A prospective, randomized, placebo controlled trial. Scan J Gastroenterol 2005; 40: 515-522
254 Archimandritis A, Tsirantonaki M, Tryphonos M et al. Ranitidine versus ranitidine plus octreotide in the treatment of acute nonvariceal upper gastrointestinal bleeding: a prospective randomized study. Curr Med Res Opin 2000; 16: 178-183
255 Lin H, Perng C, Wang K et al. Octreotide for arrest of peptic ulcer hemorrhage – a prospective randomized controlled trial. Hepatogastroenterology 1995; 42: 856-860
256 Kim I, Lee YS, Koh BS et al. Does adding somatostatin to proton pump inhibitor improve the outcome of peptic ulcer bleeding?. Korean J Crit Care Med 2008; 23: 75-78
257 Antonioli A, Gandolfo M, Rigo GD et al. Somatostatin and cimetidine in the control of acute upper gastrointestinal bleeding. A controlled multicentre study. Hepatogastroenterology 1986; 33: 71-94
258 Tisbouris P, Zintazas E, Lappas C et al. High-dose pantoprazole infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding. Am J Gastroenterol 2007; 102: 1192-1199
259 Okan A, Simsek I, Akpinar H et al. Somatostatin and ranitidine in the treatment of non-variceal upper gastrointestinal bleeding: a prospective randomized, double-blind, controlled study. Hepatogastroenterology 2000; 47: 1325-1327
260 Rutgeerts P, Avgerinos A et al. Early administration of somatostatin before endoscopy to non-cirrhotic patients with suspected peptic ulcer bleeding: The PUB double-blind, randomized, placebo-controlled trial. Gut 2006; 55: A47
261 Carbonell N, Pauwels A, Serfaty L et al. Erythromycin infusion prior to endoscopy for acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Am J Gastroenterol 2006; 101: 1211-1215
262 Coffin B, Pocard M, Panis Y et al. Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study. Gastrointest Endosc 2002; 56: 174-179
263 Frossard JL, Spahr L, Queneau PE et al. Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Gastroenterology 2002; 123: 17-23
264 Theivanayagam S, Lim RG, Cobell WJ et al. Administration of erythromycin before endoscopy in upper gastrointestinal bleeding: a meta-analysis of randomized controlled trials. Saudi J Gastroenterol 2013; 19: 205-210
265 Sussman DA, Deshpande AR, Parra JL et al. Intravenous metoclopramide to increase mucosal visualization during endoscopy in patients with acute upper gastrointestinal bleeding: a randomized, controlled study. Gastrontest Endosc 2008; 67: AB247
266 Barkun AN, Bardou M, Martel M et al. Prokinetics in acute upper GI bleeding: a meta-analysis. Gastrointest Endosc 2010; 72: 1138-1145
267 Habashi SL, Lambiase LR, Kottoor R. Prokinetics infusion prior endoscopy for acute upper gastrointestinal bleeding: A randomized, controlled, double-blind and placebo-controlled trial [abstract]. Am J Gastroenterol 2007; 102: S526
268 Winstead NS, Wilcox CM. Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost-effectiveness analysis. Aliment Pharmacol Ther 2007; 26: 1371-1377
269 Spiegel BM, Vakil NB, Ofman JJ. Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review. Arch Intern Med 2001; 161: 1393-1404
270 Tsoi KKF, Ma TKW, Sung JJY. Endoscopy for upper gastrointestinal bleeding: how urgent is it?. Nat Rev Gastroenterol Hepatol 2009; 6: 463-469
271 Sarin N, Monga N, Adams PC. Time to endoscopy and outcomes in upper gastrointestinal bleeding. Can J Gastroenterol 2009; 23: 489-493
272 Lim L, Ho K, Chan Y et al. Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. Endoscopy 2011; 43: 300-306
273 Marmo R, Del Piano M, Rotondano G et al. Mortality from nonvariceal upper gastrointestinal bleeding: is it time to differentiate the timing of endoscopy?. Gastrointest Endosc 2011; 73: AB224
274 Wysocki JD, Srivastav S, Winstead NS. A nationwide analysis of risk factors for mortality and time to endoscopy in upper gastrointestinal haemorrhage. Aliment Pharmacol Ther 2012; 36: 30-36
275 Jairath V, Kakan BC, Logan RF et al. Outcomes following acute nonvariceal upper gastrointestinal bleeding in relation to time to endoscopy: results from a nationwide study. Endoscopy 2012; 44: 723-730
276 Sachar H, Vaidya K, Laine L. Intermittent vs. continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med 2014; 174: 1755-1762
277 Sung JJ, Suen BY, Wu JC et al. Effects of intravenous and oral esomeprazole in the prevention of recurrent bleeding from peptic ulcers after endoscopic therapy. Am J Gastroenterol 2014; 109: 1005-1010
278 Mostaghni AA, Hashemi SA, Heydari ST. Comparison of oral and intravenous proton pump inhibitor on patients with high risk bleeding peptic ulcers: a prospective, randomized, controlled clinical trial. Iran Red Crescent Med J 2011; 13: 458-463
279 Yen HH, Yang CW, Su WW et al. Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy. BMC Gastroenterology 2012; 12: 66
280 Tsai JJ, Hsu YC, Perng CL et al. Oral or intravenous proton pump inhibitor in patients with peptic ulcer bleeding after successful endoscopic epinephrine injection. Br J Clin Pharmacol 2009; 67: 326-332
281 Wang CH, Ma MH, Chou HC 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. Arch Intern Med 2010; 170: 751-758
282 Mazjedizadeh AR, Hajiani E, Alavinejad P et al. High dose versus low dose intravenous pantoprazole in bleeding peptic ulcer: a randomized clinical trial. Middle East J Dig Dis 2014; 6: 137-143
283 Lau JYW, Sung JJY, Lam YH et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcer. N Engl J Med 1999; 340: 751-756
284 Wong TCF, Wong TT, Chiu PWY et al. A comparison of angiographic embolization with surgery after failed endoscopic hemostasis to bleeding peptic ulcers. Gastrointest Endosc 2011; 73: 900-908
285 Kyaw M, Tse Y, Ang D et al. Embolization versus surgery for peptic ulcer bleeding after failed endoscopic hemostasis: a meta-analysis. Endosc Int Open 2014; 2: E6-E14
286 Beggs AD, Dilworth MP, Powell SL et al. A systematic review of transarterial embolization versus emergency surgery in treatment of major nonvariceal upper gastrointestinal bleeding. Clin Exp Gastroenterol 2014; 7: 93-104
287 Smith LA, Stanley AJ, Bergman JJ et al. Hemospray application in nonvariceal upper gastrointestinal bleeding: results of the survey to evaluate the application of hemospray in the luminal tract. J Clin Gastroenterol 2014; 48: 89-92
288 Sulz M, Frei R, Meyenberger C et al. Routine use of Hemospray for gastrointestinal bleeding: prospective two-center experience in Switzerland. Endoscopy 2014; 46: 619-624
289 Skinner M, Gutteriez JP, Neumann H et al. Over-the-scope clip placement is effective rescue therapy for severe acute upper gastrointestinal bleeding. Endosc Int Open 2014; 02: E37-E40
290 Manta R, Galloro G, Mangiavillano B et al. Over-the-scope clip (OTSC) represents an effective endoscopic treatment for acute GI bleeding after failure of conventional techniques. Surg Endosc 2013; 27: 3162-3164
291 Sanchez-Delgado J, Gene E, Suarez D et al. Has H. pylori prevalence in bleeding peptic ulcer been underestimated? A meta-regression. Am J Gastroenterol 2011; 106: 398-405
292 Gisbert JP, Abraira V. Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis. Am J Gastroenterol 2006; 101: 848-863
293 Gisbert JP, Calvet X, Cosme A et al. Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding. Am J Gastroenterol 2012; 107: 1197-1204
294 Gisbert JP, Khorrami S, Carballo F et al. Meta-analysis: Helicobacter pylori eradication therapy vs. anti-secretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Aliment Pharmacol Ther 2004; 19: 617-629
295 Dixon MF, Genta RM, Yardley JH et al. Classification and grading of gastritis. The updated Sydney System. Am J Surg Pathol 1996; 20: 1161-1181
296 Witt DM, Delate T, Garcia DA et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med 2012; 172: 1484-1491
297 Qureshi W, Mittal C, Patsias I et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. Am J Cardiol 2014; 113: 662-668
298 Lee JK, Kang HW, Kim SG et al. Risks related with withholding and resuming anticoagulation in patients with non-variceal upper gastrointestinal bleeding while on warfarin therapy. Int J Clin Pract 2012; 66: 64-68
299 Goodman SG, Clare R, Pieper KS et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial. Circulation 2012; 125: 978-986
300 Stockl KM, Le L, Zakharyan A et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med 2010; 170: 704-710
301 Kreutz RP, Stanek EJ, Aubert R et al. Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study. Pharmacotherapy 2010; 30: 787-796
302 Ho PM, Maddox TM, Wang L et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937-944
303 Huang CC, Chen YC, Leu HB et al. Risk of adverse outcomes in Taiwan associated with concomitant use of clopidogrel and proton pump inhibitors in patients who received percutaneous coronary intervention. Am J Cardiol 2010; 105: 1705-1709
304 Zou JJ, Chen SL, Tan J et al. Increased risk for developing major adverse cardiovascular events in stented Chinese patients treated with dual antiplatelet therapy after concomitant use of the proton pump inhibitor. PLoS One 2014; 9: e84985
305 van Boxel OS, van Oijen MG, Hagenaars MP et al. Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. Am J Gastroenterol 2010; 105: 2430-2436
306 Munoz-Torrero JF, Escudero D, Suarez C et al. Concomitant use of proton pump inhibitors and clopidogrel in patients with coronary, cerebrovascular, or peripheral artery disease in the factores de Riesgo y ENfermedad Arterial (FRENA) registry. J Cardiovasc Pharmacol 2011; 57: 13-19
307 O’Donoghue ML, Braunwald E, Antman EM et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009; 374: 989-997
308 Hsiao FY, Mullins CD, Wen YW et al. Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome. Pharmacoepidemiol Drug Saf 2011; 20: 1043-1049
309 Banerjee S, Weideman RA, Weideman MW et al. Effect of concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention. Am J Cardiol 2011; 107: 871-878
310 Harjai KJ, Shenoy C, Orshaw P et al. Clinical outcomes in patients with the concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention: an analysis from the Guthrie Health Off-Label Stent (GHOST) investigators. Circ Cardiovasc Interv 2011; 4: 162-170
311 Aihara H, Sato A, Takeyasu N et al. Effect of individual proton pump inhibitors on cardiovascular events in patients treated with clopidogrel following coronary stenting: results from the Ibaraki Cardiac Assessment Study Registry. Catheter Cardiovasc Interv 2012; 80: 556-563
312 Tentzeris I, Jarai R, Farhan S et al. Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation. Thromb Haemost 2010; 104: 1211-1218
313 Schmidt M, Johansen MB, Robertson DJ et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther 2012; 35: 165-174
314 Rassen JA, Choudhry NK, Avorn J et al. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation 2009; 120: 2322-2329
315 Ray WA, Murray KT, Griffin MR et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med 2010; 152: 337-345
316 Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther 2010; 31: 810-823
317 Siller-Matula JM, Jilma B, Schror K et al. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J Thromb Haemost 2010; 8: 2624-2641