Antithrombotics and Gastrointestinal Prophylaxis: A Systematic Review.

Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9304686 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-4683 (Electronic) Linking ISSN: 10615377 NLM ISO Abbreviation: Cardiol Rev Subsets: MEDLINE

Publication: 1998- : Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. : Williams & Wilkins, c1993-

Fibrinolytic Agents*/therapeutic use ; Fibrinolytic Agents*/adverse effects ; Gastrointestinal Hemorrhage*/prevention & control ; Gastrointestinal Hemorrhage*/chemically induced; Humans ; Anticoagulants/therapeutic use ; Anticoagulants/adverse effects ; Histamine H2 Antagonists/therapeutic use ; Platelet Aggregation Inhibitors/therapeutic use ; Platelet Aggregation Inhibitors/adverse effects ; Proton Pump Inhibitors/therapeutic use

Antithrombotic medications include both antiplatelet and anticoagulants and are used for a wide variety of cardiovascular conditions. A common complication of antithrombotic use is gastrointestinal bleeding. As a result, gastrointestinal prophylaxis is a common consideration for patients on a single or combination antithrombotic regimen. Prophylaxis is typically achieved through use of either proton pump inhibitors or histamine 2 receptor antagonists. Current recommendations for use of gastrointestinal prophylaxis with concomitant use of antithrombotic medications are scarce. In this systematic review, we explore the current evidence and recommendations regarding gastrointestinal prophylaxis for patients on antiplatelet or anticoagulant therapy as well as combination regimens.
Competing Interests: Disclosure: The authors declare no conflict of interest.
(Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909–1917.
Williams CD, Chan AT, Elman MR, et al. Aspirin use among adults in the US: results of a national survey. Am J Prev Med. 2015;48:501–508.
Hallas J, Dall M, Andries A, et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. Bmj. 2006;333:726.
Moayyedi P, Eikelboom JW, Bosch J, et al. 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.
Schjerning Olsen AM, Lindhardsen J, Gislason GH, et al. Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study. BMJ (Clinical research ed.). 2015;351:h5096.
Iwamoto J, Saito Y, Honda A, et al. Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy. World J Gastroenterol. 2013;19:1673–1682.
Saven H, Zhong L, McFarlane IM, Co-prescription of dual-antiplatelet therapy and proton pump inhibitors: current guidelines. Cureus. 2022;14:e21885.
Cryer B. Reducing the risks of gastrointestinal bleeding with antiplatelet therapies. N Engl J Med. 2005;352:287–289.
Ma L, Elliott SN, Cirino G, et al. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proc Natl Acad Sci U S A. 2001;98:6470–6475.
Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management. World J Gastroenterol. 2017;23:1954–1963.
Vaduganathan M, Bhatt DL. Gastrointestinal bleeding with oral anticoagulation: understanding the scope of the problem. Clin Gastroenterol Hepatol. 2017;15:691–693.
Mo C, Sun G, Wang YZ, et al. PPI versus histamine H2 receptor antagonists for prevention of upper gastrointestinal injury associated with low-dose aspirin: systematic review and meta-analysis. PLoS One. 2015;10:e0131558.
Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;118:S9–31.
Green FW, Kaplan MM, Curtis LE, et al. Effect of acid and pepsin on blood coagulation and platelet aggregation: a possible contributor to prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978;74:38–43.
Vazalore (aspirin) [prescribing information]. Sparta, NJ: PLx Pharma Inc; April 2021.
US Preventive Services Task Force (USPSTF). Aspirin for the Prevention of Cardiovascular Disease: Clinical Summary. AHRQ Publication No.09-05129-EF-3, March 2009. Agency for Healthcare Research and Quality, Rockville, MD. Available at: http://www.uspreventiveservicestaskforce.org/uspstf09/aspirincvd/aspcvdsum.htm . Accessed May 5, 2022.
Iqbal AM, Lopez RA, Hai O. Antiplatelet Medications. 2022 Feb 14. In: StatPearls [Internet]. StatPearls Publishing; 2022 Jan.
Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA. 2019;321:277–287.
Zhang WT, Wang MR, Hua GD, et al. Inhibition of aspirin-induced gastrointestinal injury: systematic review and network meta-analysis. Front Pharmacol. 2021;12:730681.
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American heart association Task force on clinical practice guidelines. Circulation. 2019;140:e596–e646.
Huang ES, Strate LL, Ho WW, et al. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. 2011;124:426–433.
Mahady SE, Margolis KL, Chan A, et al. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut. 2021;70:717–724.
Yeomans N, Lanas A, Labenz J, et al. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol. 2008;103:2465–2473.
Scally B, Emberson JR, Spata E, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018;3:231–241.
Tran-Duy A, Vanmolkot FH, Joore MA, et al. Should patients prescribed long-term low-dose aspirin receive proton pump inhibitors? A systematic review and meta-analysis. Int J Clin Pract. 2015;69:1088–1111.
Li L, Geraghty OC, Mehta Z, et al.; Oxford Vascular Study. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet. 2017;390:490–499.
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;346:2033–2038.
Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352:238–244.
Taha AS, McCloskey C, Prasad R, et al. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:119–125.
Wu W, Liu J, Yu H, et al. Antiplatelet therapy with or without PPIs for the secondary prevention of cardiovascular diseases in patients at high risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Exp Ther Med. 2020;19:3595–3603.
Herbert JM, Frehel D, Vallee E, et al. Clopidogrel, a novel antiplatelet and antithrombotic agent. Cardiovascular Drug Rev. 1993;11:180–198.
Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Investig. 2004;113:340–345.
US Food and Drug Administration and Center for Drug Evaluation and Research. Plavix prescribing information. 2018:1–27. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020839s070lbl.pdf . Accessed October 2, 2019.
US Food and Drug Administration and Center for Drug Evaluation and Research. Effient prescribing information. 2019:1–19. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022307s016lbl.pdf . Accessed October 2, 2019.
US Food and Drug Administration and Center for Drug Evaluation and Research. Brilinta prescribing information. 2018:1–26. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022433s022lbl.pdf . Accessed October 2, 2019.
US Food and Drug Administration, Center for Drug Evaluation and Research. Kengreal prescribing information. 2015:0–13. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204958Orig1s000Lbl.pdf . Accessed October 2, 2019.
Abraham NS, Noseworthy PA, Inselman J, et al. Risk of gastrointestinal bleeding increases with combinations of antithrombotic agents and patient age. Clin Gastroenterol Hepatol. 2020;18:337–346.e19.
Abraham NS, Yang EH, Noseworthy PA, et al. Fewer gastrointestinal bleeds with ticagrelor and prasugrel compared with clopidogrel in patients with acute coronary syndrome following percutaneous coronary intervention. Aliment Pharmacol Ther. 2020;52:646–654.
Abraham NS, Hlatky MA, Antman EM, et al.; ACCF/ACG/AHA. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. J Am Coll Cardiol. 2010;56:2051–2066.
Frelinger AL 3rd, Lee RD, Mulford DJ, et al. A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol. 2012;59:1304–1311.
Melloni C, Washam JB, Jones WS, et al. Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review. Circ Cardiovasc Qual Outcomes. 2015;8:47–55.
Abrignani MG, Gatta L, Gabrielli D, et al. Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO). Eur J Intern Med. 2021;85:1–13.
Focks JJ, Brouwer MA, van Oijen MG, et al. Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review. Heart. 2013;99:520–527.
Gargiulo G, Costa F, Ariotti S, et al. Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial. Am Heart J. 2016;174:95–102.
Yi ZM, Qiu TT, Zhang Y, et al. Comparison of prophylactic effect of UGIB and effects on platelet function between PPIs and H 2 RAs combined with DAPT: systematic review and meta-analysis. Ther Clin Risk Manag. 2017;13:367–377.
Bhatt DL, Scheiman J, Abraham NS, et al.; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents 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.
Reaume KT, Regal RE, Dorsch MP. Indications for dual antiplatelet therapy with aspirin and clopidogrel: evidence-based recommendations for use. Ann Pharmacother. 2008;42:550–557.
Peters RJ, Mehta SR, Fox KA, et al.; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators. Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003;108:1682–1687.
Yusuf S, Zhao F, Mehta SR, et al.; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.
Diener HC, Bogousslavsky J, Brass LM, et al.; MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331–337.
Valgimigli M, Cao D, Angiolillo DJ, et al.; XIENCE 90 and XIENCE 28 Investigators. Duration of dual antiplatelet therapy for patients at high bleeding risk undergoing PCI. J Am Coll Cardiol. 2021;78:2060–2072.
Valgimigli M, Bueno H, Byrne RA, et al.; ESC Scientific Document GroupESC Committee for Practice Guidelines (CPG)ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39:213–260.
Jensen BE, Hansen JM, Larsen KS, et al. Randomized clinical trial: the impact of gastrointestinal risk factor screening and prophylactic proton pump inhibitor therapy in patients receiving dual antiplatelet therapy. J Gastroenterol. 2017;29:1118–1125.
Almufleh A, Ramirez FD, So D, et al. H2 receptor antagonists versus proton pump inhibitors in patients on dual antiplatelet therapy for coronary artery disease: a systematic review. Cardiology. 2018;140:115–123.
Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574–e651.
Hartman J, Nauka PC, Priyanka S, et al. Proton pump inhibitors are underprescribed in patients discharged on dual antiplatelet therapy after acute coronary syndrome. Gastroenterology. 2018;155:e37.
Hirsh J, Anand SS, Halperin JL, et al. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol. 2001;21:1094–1096.
Nutescu EA, Burnett A, Fanikos J, et al. Pharmacology of anticoagulants used in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016;41:15–31.
Jupalli A, Iqbal AM. Enoxaparin. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure. StatPearls Publishing; 2022 Jan. Available at: http://www.ncbi.nlm.nih.gov/books/NBK539865/ . Accessed May 6, 2022.
Wilkins T, Wheeler B, Carpenter M. Upper gastrointestinal bleeding in adults: evaluation and management. Am Fam Physician. 2020;101(5):294–300.
Costantino G, Ceriani E, Rusconi AM, et al. Bleeding risk during treatment of acute thrombotic events with subcutaneous LMWH compared to intravenous unfractionated heparin; a systematic review. PLoS One. 2012;7:e44553.
Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment. Chest. 2004;126:287S–310S.
Petty GW. Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention: a population-based study. Ann Intern Med. 1999;130:14–22.
Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med. 1993;95:315–328.
Oh HJ, Ryu KH, Park BJ, et al. The risk of gastrointestinal hemorrhage with non-vitamin K antagonist oral anticoagulants: a network meta-analysis. Medicine (Baltim). 2021;100:e25216.
Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med. 1994;330:377–381.
Barkun AN, Bardou M, Pham CQD, et al. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol. 2012;107:507–20; quiz 521.
Hirsh J, Fuster V, Ansell J, et al.; American Heart Association. American Heart Association/American College of Cardiology Foundation Guide to warfarin therapy. Circulation. 2003;107:1692–1711.
Holford NHG. Clinical pharmacokinetics and pharmacodynamics of warfarin. Clin Pharmacokinet. 1986;11:483–504.
Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease. Chest. 2012;141:e419S–e496S.
Kuruvilla M, Gurk-Turner C. A review of warfarin dosing and monitoring. Proc (Bayl Univ Med Cent). 2001;14:305–306.
Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use. Arch Intern Med. 2007;167:14141414.
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.
Lee H-J, Kim H-K, Kim B-S, et al. Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy. PLoS One. 2021;16:e0253310.
Chen WC, Chen YH, Hsu PI, et al. Gastrointestinal hemorrhage in warfarin anticoagulated patients: incidence, risk factor, management, and outcome. Biomed Res Int. 2014;2014:463767.
Abraham NS, Singh S, Alexander GC, et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ. 2015;350:h1857.
Chen A, Stecker E, A Warden B. Direct oral anticoagulant use: a practical guide to common clinical challenges. J Am Heart Assoc. 2020;9:e017559.
Rose DK, Bar B. Direct oral anticoagulant agents: pharmacologic profile, indications, coagulation monitoring, and reversal agents. J Stroke Cerebrovasc Dis. 2018;27:2049–2058.
Prescribing information. Pradaxa (dabigatran etaxilate). Boehringer Ingelheim Pharmaceuticals, Inc; 2018.
Prescribing information. Xarelto (rivaroxaban). Janssen Pharmaceuticals, Inc; 2019.
Prescribing information. Eliquis (apixaban). Bristol‐Myers Squibb Company; 2018.
Prescribing information. Savaysa (edoxaban). Daiichi Sankyo Co., LTD; 2017.
Prescribing information. Bevyxxa (Betrixaban). Portola Pharmaceuticals, Inc; 2017.
Benamouzig R, Guenoun M, Deutsch D, et al. Review article: gastrointestinal bleeding risk with direct oral anticoagulants. Cardiovasc Drugs Ther. 2021;36:973–989.
Deutsch D, Boustiere C, Ferrari E, et al. Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures. Ther Adv Gastroenterol. 2017;10:495–505.
Ruff CT, Giugliano 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 randomised trials. Lancet. 2014;383:955–962.
Ray WA, Chung CP, Murray KT, et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA. 2018;320:2221–2230.
Steffel J, Verhamme P, Potpara TS, et al.; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39:1330–1393.
Clemens A, Strack A, Noack H, et al. Anticoagulant-related gastrointestinal bleeding – could this facilitate early detection of benign or malignant gastrointestinal lesions? Ann Med. 2014;46:672–678.
Chan EW, Lau WC, Leung WK, et al. Prevention of dabigatran related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology. 2015;149:586–95.e3.
Scibelli N, Mangano A, Raynor K, et al. A retrospective review of upper gastrointestinal bleed outcomes during hospital admission while on oral anticoagulation. Cureus. 2021;13:e15061.
Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC Expert Consensus Decision Pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020;77:629–658.
Capodanno D, Angiolillo DJ. Management of antiplatelet and anticoagulant therapy in patients with atrial fibrillation in the setting of acute coronary syndromes or percutaneous coronary interventions. Circ Cardiovasc Interv. 2014;7:113–124.
Sarafoff N, Martischnig A, Wealer J, et al. Triple therapy with aspirin, prasugrel, and vitamin K antagonists in patients with drug-eluting stent implantation and an indication for oral anticoagulation. J Am Coll Cardiol. 2013;61:2060–2066.
Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007;100:1419–1426.
Eikelboom JW, Connolly SJ, Bosch J, et al.; COMPASS InvestigatorsCOMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319–1330.
Barnes GD. Combining antiplatelet and anticoagulant therapy in cardiovascular disease. Hematology. 2020;2020:642–648.
Dewilde WJ, Oirbans T, Verheugt FW, et al.; WOEST study investigators. WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107–1115.
Effron MB, Gibson CM. Dual (anticoagulant plus single antiplatelet) vs triple (anticoagulant plus dual antiplatelet) antithrombotic therapy – “Real world” experience. Prog Cardiovasc Dis. 2018;60:531–536.
Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016;134:e123–e155.
Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC Expert Consensus Decision Pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease. J Am Coll Cardiol. 2021;77:629–658.
Fiedler KA, Maeng M, Mehilli J, et al. Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent implantation. J Am Coll Cardiol. 2015;65:1619–1629.
Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423–2434.
Lopes RD, Heizer G, Aronson R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019;380:1509–1524.
Nicolau JC, Bhatt DL, Hohnloser SH, et al.; RE-DUAL PCI Steering Committee and Investigators. Dabigatran dual therapy vs warfarin triple therapy post-percutaneous coronary intervention in patients with atrial fibrillation with/without a proton pump inhibitor: a pre-specified analysis of the RE-DUAL PCI Trial. Drugs. 2020;80:995–1005.
Krag M, Perner A, Wetterslev J, et al. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2014;40:11–22.
Pongprasobchai S, Kridkratoke S, Nopmaneejumruslers C. Proton pump inhibitors for the prevention of stress-related mucosal disease in critically-ill patients: a meta-analysis. J Med Assoc Thai. 2009;92:632–637.
Alhazzani W, Alenezi F, Jaeschke RZ, et al. Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2013;41:693–705.
Barkun AN, Bardou M, Pham CQ, et al. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol. 2012;107:507–520; quiz 521.
Alshamsi F, Belley-Cote E, Cook D, et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care. 2016;20:120.
Lin PC, Chang CH, Hsu PI, et al. The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med. 2010;38:1197–1205.
Dellinger RP, Levy MM, Rhodes A, et al.; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.
Ho CW, Tse YK, Wu B, et al. The use of prophylactic gastroprotective therapy in patients with nonsteroidal anti-inflammatory drug- and aspirin-associated ulcer bleeding: a cross-sectional study. Aliment Pharmacol Ther. 2013;37:819–824.
Medlock S, Eslami S, Askari M, et al. Co-prescription of gastroprotective agents and their efficacy in elderly patients taking nonsteroidal anti-inflammatory drugs: a systematic review of observational studies. Clin Gastroenterol Hepatol. 2013;11:1259–1269.e10.
Mutlu GM, Mutlu EA, Factor P. GI complications in patients receiving mechanical ventilation. Chest. 2001;119:1222–1241.
Shuman RB, Schuster DP, Zuckerman GR. Prophylactic therapy for stress ulcer bleeding: a reappraisal. Ann Intern Med. 1987;106:562–567.

0 (Anticoagulants)
0 (Fibrinolytic Agents)
0 (Histamine H2 Antagonists)
0 (Platelet Aggregation Inhibitors)
0 (Proton Pump Inhibitors)

Date Created: 20230322 Date Completed: 20241108 Latest Revision: 20241226

20241227

10.1097/CRD.0000000000000543

36946915