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

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).

• 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