Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group

Alan N Barkun, Majid Almadi, Ernst J Kuipers, Loren Laine, Joseph Sung, Frances Tse, Grigorios I Leontiadis, Neena S Abraham, Xavier Calvet, Francis K L Chan, James Douketis, Robert Enns, Ian M Gralnek, Vipul Jairath, Dennis Jensen, James Lau, Gregory Y H Lip, Romaric Loffroy, Fauze Maluf-Filho, Andrew C Meltzer, Nageshwar Reddy, John R Saltzman, John K Marshall, Marc Bardou, Alan N Barkun, Majid Almadi, Ernst J Kuipers, Loren Laine, Joseph Sung, Frances Tse, Grigorios I Leontiadis, Neena S Abraham, Xavier Calvet, Francis K L Chan, James Douketis, Robert Enns, Ian M Gralnek, Vipul Jairath, Dennis Jensen, James Lau, Gregory Y H Lip, Romaric Loffroy, Fauze Maluf-Filho, Andrew C Meltzer, Nageshwar Reddy, John R Saltzman, John K Marshall, Marc Bardou

Abstract

Description: This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations.

Methods: An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional.

Recommendations: Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.

References

    1. Laine L, Yang H, Chang SC, et al. Trends for incidence of hospitalization and death due to GI complications in the United States from 2001 to 2009. Am J Gastroenterol. 2012;107:1190–5; quiz 1196. doi:10.1038/ajg.2012.168
    1. Rosenstock SJ, Møller MH, Larsson H, et al. Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery. Am J Gastroenterol. 2013;108:1449–57. doi:10.1038/ajg.2013.162
    1. Barkun A, Bardou M, Marshall JK; Nonvariceal Upper GI Bleeding Consensus Conference Group. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2003;139:843–57.
    1. Barkun AN, Bardou M, Kuipers EJ, et al.; International Consensus Upper Gastrointestinal Bleeding Conference Group. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010; 152:101–13. doi:10.7326/0003-4819-152-2-201001190-00009
    1. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107:345–60; quiz 361. doi:10.1038/ajg.2011.480
    1. 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 nonvariceal upper GI bleeding. Gastrointest Endosc. 2012;75:1132–8. [PMID: 22624808] doi:10.1016/j.gie.2012.02.033
    1. National Institute for Health and Care Excellence. Acute upper gastrointestinal bleeding: management (NICE clinical guideline 141), 2012. Last update: November 2018. Accessed at on 12 August 2019
    1. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: european society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy. 2015;47:a1–46. doi:10.1055/s-0034-1393172
    1. Sung JJ, Chiu PW, Chan FKL, et al. Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018. Gut. 2018;67:1757–1768. doi:10.1136/gutjnl-2018-316276
    1. Abraham NS, Hartman C, Richardson P, et al. Risk of lower and upper gastrointestinal bleeding, transfusions, and hospitalizations with complex antithrombotic therapy in elderly patients. Circulation. 2013;128:1869–77. doi:10.1161/CIRCULATIONAHA.113.004747
    1. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or nonrandomised studies of healthcare interventions, or both. BMJ. 2017; 358:j4008. doi:10.1136/bmj.j4008
    1. Guyatt GH, Oxman AD, Vist GE, et al.; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6. doi:10.1136/
    1. Guyatt GH, Schünemann HJ, Djulbegovic B, et al. Guideline panels should not GRADE good practice statements. J Clin Epidemiol. 2015;68:597–600. doi:10.1016/j.jclinepi.2014.12.011
    1. Dalkey N An experimental study of group opinion: the Delphi method. Futures. 1969;1:408–26.
    1. Schünemann HJ, Mustafa R, Brozek J, et al.; GRADE Working Group. GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health. J Clin Epidemiol. 2016;76:89–98. doi:10.1016/j.jclinepi.2016.01.032
    1. Alonso-Coello P, Oxman AD, Moberg J, et al.; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016;353:i2089. doi:10.1136/bmj.i2089
    1. Alonso-Coello P, Schünemann HJ, Moberg J, et al.; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016;353:i2016. doi:10.1136/bmj.i2016
    1. Guyatt GH, Oxman AD, Kunz R, et al.; GRADE Working Group. Going from evidence to recommendations. BMJ. 2008;336:1049–51. doi:10.1136/
    1. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013:CD000567. doi:10.1002/14651858.CD000567.pub6
    1. Chávez-Negrete A, Majluf Cruz S, Frati Munari A, et al. Treatment of hemorrhagic shock with intraosseous or intravenous infusion of hypertonic saline dextran solution. Eur Surg Res. 1991;23:123–9.
    1. Annane D, Siami S, Jaber S, et al.; CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310:1809–17. doi:10.1001/jama.2013.280502
    1. Semler MW, Self WH, Wanderer JP, et al.; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:829839. doi:10.1056/NEJMoa1711584
    1. Kowalenko T, Stern S, Dronen S, et al. Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model. J Trauma. 1992;33:349–53; discussion 361–2.
    1. Stern SA, Dronen SC, Birrer P, et al. Effect of blood pressure on hemorrhage volume and survival in a near-fatal hemorrhage model incorporating a vascular injury. Ann Emerg Med. 1993;22:155–63.
    1. Kwan I, Bunn F, Chinnock P, et al. Timing and volume of fluid administration for patients with bleeding. Cochrane Database Syst Rev. 2014:CD002245. doi:10.1002/14651858.CD002245.pub2
    1. Schreiber MA, Meier EN, Tisherman SA, et al.; ROC Investigators. A controlled resuscitation strategy is feasible and safe in hypotensive trauma patients: results of a prospective randomized pilot trial. J Trauma Acute Care Surg. 2015;78:687–95; discussion 695–7. doi:10.1097/TA.0000000000000600
    1. Carrick MM, Morrison CA, Tapia NM, et al. Intraoperative hypotensive resuscitation for patients undergoing laparotomy or thoracotomy for trauma: early termination of a randomized prospective clinical trial. J Trauma Acute Care Surg. 2016;80:886–96. doi:10.1097/TA.0000000000001044
    1. 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;373:42–7. doi:10.1016/S0140-6736(08)61769-9
    1. Ramaekers R, Mukarram M, Smith CA, et al. The predictive value of preendoscopic risk scores to predict adverse outcomes in emergency department patients with upper gastrointestinal bleeding: a systematic review. Acad Emerg Med. 2016;23:1218–1227. doi:10.1111/acem.13101
    1. Laursen SB, Dalton HR, Murray IA, et al.; Upper Gastrointestinal Hemorrhage International Consortium. Performance of new thresholds of the Glasgow Blatchford score in managing patients with upper gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2015;13: 115–21.e2. doi:10.1016/j.cgh.2014.07.023
    1. Stanley AJ, Laine L, Dalton HR, et al.; International Gastrointestinal Bleeding Consortium. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study. BMJ. 2017;356:i6432. doi:10.1136/bmj.i6432
    1. Saltzman JR, Tabak YP, Hyett BH, et al. A simple risk score accurately predicts in-hospital mortality, length of stay, and cost in acute upper GI bleeding. Gastrointest Endosc. 2011;74:1215–24. doi:10.1016/j.gie.2011.06.024
    1. Odutayo A, Desborough MJ, Trivella M, et al. Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials. Lancet Gastroenterol Hepatol. 2017;2:354–360. doi:10.1016/S2468-1253(17)30054-7
    1. Jairath V, Kahan BC, Gray A, et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137–44. doi:10.1016/S0140-6736(14)61999-1
    1. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:1121. doi:10.1056/NEJMoa1211801
    1. Carson JL, Stanworth SJ, Roubinian N, et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016;10:CD002042.
    1. Holst LB, Petersen MW, Haase N, et al. Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. BMJ. 2015;350:h1354. doi:10.1136/bmj.h1354
    1. Shander A, Hofmann A, Ozawa S, et al. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion. 2010;50:753–65. doi:10.1111/j.1537-2995.2009.02518.x
    1. Blair SD, Janvrin SB, McCollum CN, et al. Effect of early blood transfusion on gastrointestinal haemorrhage. Br J Surg. 1986;73: 783–5.
    1. Docherty AB, O’Donnell R, Brunskill S, et al. Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis. BMJ. 2016;352:i1351. doi:10.1136/bmj.i1351
    1. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA. 2016;316:2025–2035. doi:10.1001/jama.2016.9185
    1. Nagata N, Sakurai T, Moriyasu S, et al. Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on rebleeding and thromboembolism in acute gastrointestinal bleeding. PLoS One. 2017;12:e0183423. doi:10.1371/journal.pone.0183423
    1. Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385:2077–87. doi:10.1016/S0140-6736(14)61685-8
    1. Sarode R, Milling TJ Jr, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasmacontrolled, phase IIIb study. Circulation. 2013;128:1234–43. doi:10.1161/CIRCULATIONAHA.113.002283
    1. Choudari CP, Rajgopal C, Palmer KR. Acute gastrointestinal haemorrhage in anticoagulated patients: diagnoses and response to endoscopic treatment. Gut. 1994;35:464–6.
    1. Thomopoulos KC, Mimidis KP, Theocharis GJ, et al. Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: endoscopic findings, clinical management and outcome. World J Gastroenterol. 2005;11:1365–8.
    1. National Institute for Health and Care Excellence. Blood transfusion (NICE clinical guideline 24), 2015. Last update: November 2015. Accessed at on 12 August 2019.
    1. Connolly SJ, Milling TJ Jr, Eikelboom JW, et al.; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41. doi:10.1056/NEJMoa1607887
    1. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med. 2017;377:431441. doi:10.1056/NEJMoa1707278
    1. Spiegel BM, Vakil NB, Ofman JJ. Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review. Arch Intern Med. 2001;161:1393–404.
    1. 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;22:267–71. ]
    1. 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;50:755–61.
    1. 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.
    1. Kumar NL, Cohen AJ, Nayor J, et al. Timing of upper endoscopy influences outcomes in patients with acute nonvariceal upper GI bleeding. Gastrointest Endosc. 2017;85:945–952.e1. doi:10.1016/j.gie.2016.09.029
    1. Lim LG, Ho KY, Chan YH, et al. Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. Endoscopy. 2011;43: 300–6. doi:10.1055/s-0030-1256110
    1. Laursen SB, Leontiadis GI, Stanley AJ, et al. Relationship between timing of endoscopy and mortality in patients with peptic ulcer bleeding: a nationwide cohort study. Gastrointest Endosc. 2017; 85:936–944.e3. doi:10.1016/j.gie.2016.08.049
    1. Xia XF, Chiu PWY, Tsoi KKF, et al. The effect of off-hours hospital admission on mortality and clinical outcomes for patients with upper gastrointestinal hemorrhage: a systematic review and meta-analysis of 20 cohorts. United European Gastroenterol J. 2018;6:367–381. doi:10.1177/2050640617732651
    1. Cho SH, Lee YS, Kim YJ, et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2018;16:370–377. doi:10.1016/j.cgh.2017.06.029
    1. Ahn DW, Park YS, Lee SH, et al. Clinical outcome of acute nonvariceal upper gastrointestinal bleeding after hours: the role of urgent endoscopy. Korean J Intern Med. 2016;31:470–8. doi:10.3904/kjim.2014.099
    1. Targownik LE, Murthy S, Keyvani L, et al. The role of rapid endoscopy for high-risk patients with acute nonvariceal upper gastrointestinal bleeding. Can J Gastroenterol. 2007;21:425–9.
    1. Tai CM, Huang SP, Wang HP, et al. High-risk ED patients with nonvariceal upper gastrointestinal hemorrhage undergoing emergency or urgent endoscopy: a retrospective analysis. Am J Emerg Med. 2007;25:273–8.
    1. Garcia-Tsao G, Sanyal AJ, Grace ND, et al.; Practice Guidelines Committee of American Association for Study of Liver Diseases. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Am J Gastroenterol. 2007;102:2086–102.
    1. de Franchis R; Baveno V Faculty. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2010;53:762–8. doi:10.1016/j.jhep.2010.06.004
    1. 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; quiz 1–2. doi:10.1016/j.cgh.2008.08.016
    1. 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;69:786–99. doi:10.1016/j.gie.2008.05.031
    1. 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:CD005584. doi:10.1002/14651858.CD005584.pub3
    1. Baracat F, Moura E, Bernardo W, et al. Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials. Surg Endosc. 2016;30:2155–68. doi:10.1007/s00464-015-4542-x
    1. Ljubicic N, Budimir I, Biscanin A, et al. Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding. World J Gastroenterol. 2012;18:2219–24. doi:10.3748/wjg.v18.i18.2219
    1. Cui J, Huang LY, Liu YX, et al. Efficacy of endoscopic therapy for gastrointestinal bleeding from Dieulafoy’s lesion. World J Gastroenterol. 2011;17:1368–72. doi:10.3748/wjg.v17.i10.1368
    1. Grgov S, Radovanovic-Dinic B, Tasic T. Could application of epinephrine improve hemostatic efficacy of hemoclips for bleeding peptic ulcers? A prospective randomized study. Vojnosanit Pregl. 2013;70:824–9.
    1. Chung IK, Ham JS, Kim HS, et al. Comparison of the hemostatic efficacy of the endoscopic hemoclip method with hypertonic salineepinephrine injection and a combination of the two for the management of bleeding peptic ulcers. Gastrointest Endosc. 1999;49:13–8.
    1. Kwek BEA, Ang TL, Ong PLJ, et al. TC-325 versus the conventional combined technique for endoscopic treatment of peptic ulcers with high-risk bleeding stigmata: A randomized pilot study. J Dig Dis. 2017;18:323–329. doi:10.1111/1751-2980.12481
    1. Chen YI, Barkun AN. Hemostatic powders in gastrointestinal bleeding: a systematic review. Gastrointest Endosc Clin N Am. 2015; 25:535–52. doi:10.1016/j.giec.2015.02.008
    1. Haddara S, Jacques J, Lecleire S, et al. A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the “GRAPHE” registry). Endoscopy. 2016;48:1084–1095.
    1. Chen YI, Barkun A, Nolan S. Hemostatic powder TC-325 in the management of upper and lower gastrointestinal bleeding: a twoyear experience at a single institution. Endoscopy. 2015;47:167–71. doi:10.1055/s-0034-1378098
    1. Hagel AF, Albrecht H, Nägel A, et al. The application of hemospray in gastrointestinal bleeding during emergency endoscopy. Gastroenterol Res Pract. 2017;2017:3083481. doi:10.1155/2017/3083481
    1. Barkun AN, Adam V, Lu Y, et al. Using hemospray improves the cost-effectiveness ratio in the management of upper gastrointestinal nonvariceal bleeding. J Clin Gastroenterol. 2018;52:36–44. doi:10.1097/MCG.0000000000000709
    1. 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: 1370–4.
    1. Jensen DM, Kovacs TOG, Ohning GV, et al. Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes of patients with severe nonvariceal upper gastrointestinal hemorrhage. Gastroenterology. 2017;152:1310–1318.e1. doi:10.1053/j.gastro.2017.01.042
    1. 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;52:149–60.
    1. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev. 2006:CD002094.
    1. Neumann I, Letelier LM, Rada G, et al. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Cochrane Database Syst Rev. 2013:CD007999. doi:10.1002/14651858.CD007999.pub2
    1. Leontiadis GI, Sreedharan A, Dorward S, et al. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technol Assess. 2007;11:iii-iv, 1–164.
    1. Barkun AN, Adam V, Sung JJ, et al. Cost effectiveness of high-dose intravenous esomeprazole for peptic ulcer bleeding. Pharmacoeconomics. 2010;28:217–30. doi:10.2165/11531480-000000000-00000
    1. 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;6:418–25. doi:10.1016/j.cgh.2007.12.037
    1. Lu Y, Adam V, Teich V, et al. Timing or dosing of intravenous proton pump inhibitors in acute upper gastrointestinal bleeding has low impact on costs. Am J Gastroenterol. 2016;111:1389–1398. doi:10.1038/ajg.2016.157
    1. Cheng HC, Wu CT, Chang WL, et al. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut. 2014;63:1864–72. doi:10.1136/gutjnl-2013-306531
    1. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002;346:2033–8.
    1. Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344:967–73.
    1. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352:238–44.
    1. Lai KC, Chu KM, Hui WM, et al. Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications. Clin Gastroenterol Hepatol. 2006;4:860–5.]
    1. Chan FK, Kyaw M, Tanigawa T, et al. Similar efficacy of proton-pump inhibitors vs H2-receptor antagonists in reducing risk of upper gastrointestinal bleeding or ulcers in high-risk users of low-dose aspirin. Gastroenterology. 2017;152:105–110.e1. doi:10.1053/j.gastro.2016.09.006
    1. Khan MY, Siddiqui WJ, Alvarez C, et al. Reduction in postpercutaneous coronary intervention angina in addition to gastrointestinal events in patients on combined proton pump inhibitors and dual antiplatelet therapy: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30:847–853. doi:10.1097/MEG.0000000000001125
    1. Hu W, Tong J, Kuang X, et al. Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel: a meta-analysis. Medicine (Baltimore). 2018; 97:e9638. doi:10.1097/MD.0000000000009638
    1. Bhatt DL, Cryer BL, Contant CF, et al.; COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909–17. doi:10.1056/NEJMoa1007964
    1. Wei P, Zhang YG, Ling L, et al. Effects of the short-term application of pantoprazole combined with aspirin and clopidogrel in the treatment of acute STEMI. Exp Ther Med. 2016;12:2861–2864.
    1. Ren YH, Zhao M, Chen YD, et al. Omeprazole affects clopidogrel efficacy but not ischemic events in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention. Chin Med J (Engl). 2011;124:856–61.
    1. Wu H, Jing Q, Wang J, et al. Pantoprazole for the prevention of gastrointestinal bleeding in high-risk patients with acute coronary syndromes. J Crit Care. 2011;26:434.e1–6. doi:10.1016/j.jcrc.2010.12.007
    1. Chan FK, Ching JY, Suen BY, et al. Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users. Gastroenterology. 2013;144:528–35. doi:10.1053/j.gastro.2012.12.038
    1. Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016;151:1105–1112.e10. doi:10.1053/j.gastro.2016.08.054
    1. Chan EW, Lau WC, Leung WK, et al. Prevention of dabigatranrelated gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology. 2015;149:586–95.e3. doi:10.1053/j.gastro.2015.05.002
    1. Lin KJ, Hernández-Daz S, García RodrƖģuez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology. 2011; 141:71–9. doi:10.1053/j.gastro.2011.03.049
    1. Massó González EL, García Rodríguez LA. Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study. Aliment Pharmacol Ther. 2008;28: 629–37. doi:10.1111/j.1365-2036.2008.03780.x
    1. Lanas A, García-Rodríguez LA, Arroyo MT, et al.; Investigators of the Asociación Española de Gastroenterología (AEG). Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol. 2007;102:507–15.
    1. Islam MM, Poly TN, Walther BA, et al. Adverse outcomes of long-term use of proton pump inhibitors: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30:1395–1405. doi:10.1097/MEG.0000000000001198
    1. Hussain S, Siddiqui AN, Habib A, et al. Proton pump inhibitors’ use and risk of hip fracture: a systematic review and meta-analysis. Rheumatol Int. 2018;38:1999–2014. doi:10.1007/s00296-018-4142-x
    1. Nochaiwong S, Ruengorn C, Awiphan R, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018;33:331–342. doi:10.1093/ndt/gfw470
    1. Hafiz RA, Wong C, Paynter S, et al. The risk of community-acquired enteric infection in proton pump inhibitor therapy: systematic review and meta-analysis. Ann Pharmacother. 2018;52:613–622. doi:10.1177/1060028018760569
    1. Cao F, Chen CX, Wang M, et al. Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of Clostridium difficile infection. J Hosp Infect. 2018;98:4–13. doi:10.1016/j.jhin.2017.08.017
    1. Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology. 2017;153:35–48. doi:10.1053/j.gastro.2017.04.047
    1. Bosch J, Eikelboom JW, Connolly SJ, et al. Rationale, design and baseline characteristics of participants in the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial. Can J Cardiol. 2017;33:1027–1035. doi:10.1016/j.cjca.2017.06.001
    1. Moayyedi P, Eikelboom JW, Bosch J, et al.; COMPASS Investigators. Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2019;157:403–412.e5. doi:10.1053/j.gastro.2019.04.041
    1. Moayyedi P, Eikelboom JW, Bosch J, et al.; COMPASS Investigators. Safety of proton pump inhibitors based on a large, multiyear, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157:682–691.e2. doi:10.1053/j.gastro.2019.05.056
    1. Wong GLH, Lau LHS, Ching JYL, et al. Prevention of recurrent idiopathic gastroduodenal ulcer bleeding: a double-blind, randomised trial. Gut. 2019. doi:10.1136/gutjnl-2019-318715
    1. Baracat FI, de Moura DTH, Brunaldi VO, et al. Randomized controlled trial of hemostatic powder versus endoscopic clipping for non-variceal upper gastrointestinal bleeding. Surg Endosc. 2019. doi:10.1007/s00464-019-06769-z
    1. Toka B, Eminler AT, Karacaer C, et al. Comparison of monopolar hemostatic forceps with soft coagulation versus hemoclip for peptic ulcer bleeding: a randomized trial (with video). Gastrointest Endosc. 2019;89:792–802. doi:10.1016/j.gie.2018.10.011
    1. Kantowski M, Schoepfer AM, Settmacher U, et al. Assessment of endoscopic Doppler to guide hemostasis in high risk peptic ulcer bleeding. Scand J Gastroenterol. 2018;53:1311–1318. doi:10.1080/00365521.2018.1509121
    1. Schmidt A, Gölder S, Goetz M, et al. Over-the-scope clips are more effective than standard endoscopic therapy for patients with recurrent bleeding of peptic ulcers. Gastroenterology. 2018;155: 674–686.e6. doi:10.1053/j.gastro.2018.05.037

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe