Clinical outcomes of non-variceal upper gastrointestinal bleeding and its relation to aspirin and anticoagulants.
DOI:
https://doi.org/10.3889/oamjms.2020.3222Keywords:
Non-variceal upper gastrointestinal bleeding, Anticoagulants, AntiplateletAbstract
BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a life-threatening emergency that requires an urgent management. Antiplatelet (e.g., aspirin) and anticoagulant drugs are widely chronically used in various cardiac and coronary artery diseases. These drugs increase the risk of NVUGIB as they may cause ulceration of the upper gastrointestinal (GI) mucosa directly or may cause bleeding or rebleeding. The management of NVUGIB is complicated as the risk between GI bleeding episodes and cardiovascular attacks needs to be well managed.
AIM: The aim of this study is to determine the impact of antiplatelets (aspirin) and anticoagulants use on the morbidity, mortality, and clinical outcomes in patients presented with non-variceal GI bleeding.
PATIENTS AND METHODS: A total of 105 patients presented with melena and/or hematemesis and diagnosed by upper GI endoscopy were enrolled in a prospective cohort study. Patients were sub-grouped according to their use of antiplatelets, anticoagulants, or none (controls). Patients were excluded if they had portal hypertension or nonsteroidal anti-inflammatory drugs (NSAIDs) use and divided into five groups: Group I – patients who had not taken anticoagulants and antiplatelet; Group II – patients on heparin, warfarin, and LMWH only; Group III – patients on aspirin only; Group IV – patients on clopidogrel and ticlopidine with or without aspirin; and Group V – patients on combined anticoagulants and antiplatelet. All patients were subjected to clinical, laboratory (complete blood count, liver function tests, renal function tests, prothrombin time, and partial thromboplastin time), and endoscopic investigations. Clinical details were reported including admission, blood transfusion, rebleeding, and mortality.
RESULTS: Full medical history revealed that 43 patients were diabetic, 45 patients were cardiac, and 67 patients were hypertensive. Regarding the history of analgesic drug intake, 38 patients used NSAIDs and 29 of them used non-selective NSAIDs and 8 patients used selective NSAIDs. There were non-significant differences among the studied groups with NVUGIB regarding sex, hematemesis only presentation, melena only presentation, liver function tests, and endoscopic findings. On the other hand, there were statistically significant differences between the studied groups with NVGIB regarding increasing age, NSAIDs use whatever selective or non-selective, decrease level of HB, WBCs, serum albumin, bleeding profile, kidney function tests, clinical presentation in the form of hematemesis and melena, need for blood transfusion, history of associated diseases, especially being cardiac patients, rebleeding after 6 and 12 months, and mortality.
CONCLUSION: Aspirin intake may be associated with less favorable clinical outcomes in patients with NVUGIB, while combined anticoagulants and antiplatelets seem to be associated with the worse outcomes.
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Hermansson M, Ekedahl A, Ranstam J, Zilling T. Decreasing incidence of peptic ulcer complications after the introduction of the proton pump inhibitors, a study of the Swedish population from 1974-2002. BMC Gastroenterol. 2009;9:25. https://doi. org/10.1186/1471-230x-9-25 PMid:19379513
Loperfido S, Baldo V, Piovesana E, Bellina L, Rossi K, Groppo M, et al. Changing trends in acute upper-GI bleeding: A population- based study. Gastrointest Endosc. 2009;70(2):212-24. https:// doi.org/10.1016/j.gie.2008.10.051 PMid:19409558
Kim SY, Hyun JJ, Jung SW, Lee SW. Management of non- variceal upper gastrointestinal bleeding. Clin Endosc. 2012;45(3):220-3. https://doi.org/10.5946/ce.2012.45.3.220 PMid:22977806
Marmo R, Koch M, Cipolletta L, Capurso L, Grossi E, Cestari R, et al. Predicting mortality in non-variceal upper gastrointestinal bleeders: Validation of the Italian PNED score and prospective comparison with the rockall score. Am J Gastroenterol. 2010;105(6):1284-91. https://doi.org/10.1038/ajg.2009.687 PMid:20051943
Biecker E, Heller J, Schmitz V, Lammert F, Sauerbruch T. Diagnosis and management of upper gastrointestinal bleeding. Dtsch Arztebl Int. 2008;105(5):85-94. https://doi.org/10.3238/ arztebl.2008.0085 PMid:19633792
NICE Clinical Guideline: Acute Upper Gastrointestinal Bleeding: Management; 2015. Available from: http://www.guidance.nice. org.uk/cg. [Last accessed on 2019 May 11].
British Society of Gastroenterology Endoscopy Committee, Palmer KR. Non-variceal upper gastrointestinal haemorrhage: Guidelines. Gut. 2002;51(Suppl 4):iv1-6. PMid:12208839
Biecker E. Diagnosis and therapy of non-variceal upper gastrointestinal bleeding. World J Gastrointest Pharmacol Ther. 2015;6(4):172-82. https://doi.org/10.4292/wjgpt.v6.i4.172 PMid:26558151
Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101-13. PMid:20083829
Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60. PMid:22310222
Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;7:CD005415. https://doi. org/10.1002/14651858.cd005415.pub2 PMid:20614440
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(11):1755-62. https://doi.org/10.1001/jamainternmed.2014.4056
PMid:25201154
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(2):339-51. https://doi.org/10.1016/j.gie.2008.03.1122 PMid:18656600
Brullet E, Campo R, Calvet X, Guell M, Garcia-Monforte N, Cabrol J. A randomized study of the safety of outpatient care for patients with bleeding peptic ulcer treated by endoscopic injection. Gastrointest Endosc. 2004;60(1):15-21. https://doi. org/10.1016/s0016-5107(04)01314-8 PMid:15229419
Lau JY, Sung JJ, Lee KK, Yung MY, Wong SK, Wu JC, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med. 2000;343(5):310-6. https://doi.org/10.1056/ nejm200008033430501 PMid:10922420
Zargar SA, Javid G, Khan BA, Yattoo GN, Shah AH, Gulzar GM, et al. Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: Prospective randomized controlled trial. J Gastroenterol Hepatol. 2006;21(4):716-21. https://doi. org/10.1111/j.1440-1746.2006.04292.x PMid:16677158
Barkun AN, Herba K, Adam V, Kennedy W, Fallone CA, Bardou M. High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: A cost-effectiveness analysis. Aliment Pharmacol Ther. 2004;19(5):591-600. https://doi.org/10.1046/j.1365-2036.2004.01808.x PMid:14987328
Lee KK, You JH, Wong IC, Kwong SK, Lau JY, Chan TY, et al. Cost-effectiveness analysis of high-dose omeprazole infusion as adjuvant therapy to endoscopic treatment of bleeding peptic ulcer. Gastrointest Endosc. 2003;57(2):160-4. https://doi.org/10.1067/mge.2003.74 PMid:12556776
Laine L, Peterson WL. Bleeding peptic ulcer. N Engl J Med. 1994;331(11):717-27. https://doi.org/10.1056/ nejm199409153311107 PMid:8058080
Lau JY, Sung JJ, Lam YH, Chan AC, Ng EK, Lee DW, et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. N Engl J Med. 1999;340(10):751-6. https://doi.org/10.1056/nejm199903113401002 PMid:10072409
Ripoll C, Bañares R, Beceiro I, Menchén P, Catalina MV, Echenagusia A, et al. Comparison of transcatheter arterial embolization and surgery for treatment of bleeding peptic ulcer after endoscopic treatment failure. J Vasc Interv Radiol. 2004;15(5):447-50. https://doi.org/10.1097/01. rvi.0000126813.89981.b6 PMid:15126653
Sung JJ, Chung SC, Ling TK, Yung MY, Leung VK, Ng EK, et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995;332(3):139-42. https:// doi.org/10.1056/nejm199501193320302 PMid:7800005
Udd M, Miettinen P, Palmu A, Julkunen R. Effect of short- term treatment with regular or high doses of omeprazole on the detection of Helicobacter pylori in bleeding peptic ulcer patients. Scand J Gastroenterol. 2003;38(6):588-93. https://doi. org/10.1016/s0016-5085(03)80873-9 PMid:12825865
Chan FK, Hung LC, Suen BY, Wu JC, Lee KC, Leung VK, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002;347:2104-10. https://doi.org/10.1056/nejmoa021907 PMid:12501222
Chan FK, Wong VW, Suen BY, Wu JC, Ching JY, Hung LC, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: A double-blind, randomised trial. Lancet. 2007;369(9573):1621-6. https://doi.org/10.1016/ s0739-5930(08)79176-1 PMid:17499604
Scheiman JM, Yeomans ND, Talley NJ, Vakil N, Chan FK, Tulassay Z, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-10. https://doi. org/10.1111/j.1572-0241.2006.00499.x PMid:16494585
Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(23):2999-3054. https:// doi.org/10.12968/bjca.2011.6.11.547 PMid:21873419
Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347(13):969-74. https://doi.org/10.1056/nejmoa020496 PMid:12324552
Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: Meta-analysis with estimates of risk and benefit. Ann Intern Med. 2005;143(4):241-50. https://doi. org/10.7326/0003-4819-143-4-200508160-00005 PMid:16103468
Sørensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Andersson C, Jørgensen C, et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: A retrospective analysis of nationwide registry data. Lancet. 2009;374(9706):1967-74. https://doi.org/10.1016/ s0140-6736(09)61751-7 PMid:20006130
Targownik LE, Nabalamba A. Trends in management and outcomes of acute nonvariceal upper gastrointestinal bleeding: 1993-2003. Clin Gastroenterol Hepatol. 2006;4(12):1459-66. https://doi.org/10.1016/j.cgh.2006.08.018
PMid:17101296
Strate LL. Lower GI bleeding: Epidemiology and diagnosis. Gastroenterol Clin North Am. 2005;34(4):643-64. PMid:16303575
van Leerdam ME, Vreeburg EM, Rauws EA, Geraedts AA, Tijssen JG, Reitsma JB, et al. Acute upper GI bleeding: Did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. Am J Gastroenterol. 2003;98(7):1494-9. https://doi. org/10.1111/j.1572-0241.2003.07517.x PMid:12873568
Nutescu EA, Shapiro NL, Chevalier A, Amin AN. A pharmacologic overview of current and emerging anticoagulants. Cleve Clin J Med. 2005;72(Suppl 1):S2-6. https://doi.org/10.3949/ccjm.72. suppl_1.s2 PMid:15853173
Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation developed with the special contribution of the European Heart Rhythm Association. Europace. 2012;14(10):1385-413. https:// doi.org/10.3410/f.718304414.793499785 PMid:22923145
Jennings LK. Role of platelets in atherothrombosis. Am J Cardiol. 2009;103(Suppl 3):4A-10. PMid:19166707
Muñoz-Esparza C, Jover E, Hernández-Romero D, Saura D, Valdés M, Lip GY, et al. Interactions between clopidogrel and proton pump inhibitors: A review of evidence. Curr Med Chem. 2011;18(16):2386-400. https://doi.org/10.2174/092986711795843245 PMid:21568918
Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301(9):937-44. https://doi. org/10.1001/jama.2009.261 PMid:19258584
Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180(7):713-8. https://doi.org/10.1503/cmaj.082001 PMid:19176635
Moayyedi P, Sadowski DC. Proton pump inhibitors and clopidogrel - hazardous drug interaction or hazardous interpretation of data? Can J Gastroenterol. 2009;23(4):251-2. https://doi.org/10.1155/2009/868946 PMid:19373416
Melloni C, Washam JB, Jones WS, Halim SA, Hasselblad V, Mayer SB, 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(1):47-55. https://doi.org/10.1161/ circoutcomes.114.001177 PMid:25587094
Dunn SP, Steinhubl SR, Bauer D, Charnigo RJ, Berger PB, Topol EJ. Impact of proton pump inhibitor therapy on the efficacy of clopidogrel in the CAPRIE and CREDO trials. J Am Heart Assoc. 2013;2(1):e004564. https://doi.org/10.1161/ jaha.112.004564 PMid:23525436
Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360(4):363-75. https://doi.org/10.1056/nejmoa0808227 PMid:19106083
Gutermann IK, Niggemeier V, Zimmerli LU, Holzer BM, Battegay E, Scharl M. Gastrointestinal bleeding and anticoagulant or antiplatelet drugs: Systematic search for clinical practice guidelines. Medicine (Baltimore). 2015;94(1):e377. https://doi.org/10.1097/md.0000000000000377 PMid:25569664
GarcÃa RodrÃguez LA, Lin KJ, Hernández-DÃaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123(10):1108-15. https://doi.org/10.1161/circulationaha.110.973008 PMid:21357821
Sostres C, Lanas A. Should prophylactic low-dose aspirin therapy be continued in peptic ulcer bleeding? Drugs. 2011;71(1):1-10. https://doi.org/10.2165/11585320-000000000-00000 PMid:21175237
Sung JJ, Lau JY, Ching JY, Wu JC, Lee YT, Chiu PW, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: A randomized trial. Ann Intern Med. 2010;152(1):1-9. https://doi. org/10.7326/0003-4819-152-1-201001050-00179 PMid:19949136
Ortiz V, Ortuño J, RodrÃguez-Soler M, Iborra M, Garrigues V, Ponce J. Outcome of non-variceal acute upper gastrointestinal bleeding in patients with antithrombotic therapy. Digestion. 2009;80(2):89-94. https://doi.org/10.1159/000219345 PMid:19828953
LanasA,AabakkenL,FonsecaJ,MunganZA,PapatheodoridisGV, Piessevaux H, et al. Clinical predictors of poor outcomes among patients with nonvariceal upper gastrointestinal bleeding in Europe. Aliment Pharmacol Ther. 2011;33(11):1225-33. https:// doi.org/10.1111/j.1365-2036.2011.04651.x PMid:21480935
Hearnshaw SA, Logan RF, Lowe D, Travis SP, Murphy MF, Palmer KR. Acute upper gastrointestinal bleeding in the UK: Patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut. 2011;60(10):1327-35. https://doi.org/10.1136/gut.2010.228437 PMid:21490373
Modaber AA, Hammad A, Aliyev V. Effects of aspirin and anticoagulants on morbidity and mortality in patients with non-variceal upper gastrointestinal bleeding. Int J Hepatol Gastroenterol. 2017;3(3):71-8.
Wehbeh A, Tamim HM, Abu Daya H, Abou Mrad R, Badreddine RJ, Eloubeidi MA, et al. Aspirin has a protective effect against adverse outcomes in patients with nonvariceal upper gastrointestinal bleeding. Dig Dis Sci. 2015;60(7):2077-87. https://doi.org/10.1007/s10620-015-3604-1 PMid:25732717
Souk KM, Tamim HM, Abu Daya HA, Rockey DC, Barada KA. Aspirin use for primary prophylaxis: Adverse outcomes in non- variceal upper gastrointestinal bleeding. World J Gastrointest Surg. 2016;8(7):501-7. https://doi.org/10.4240/wjgs.v8.i7.501 PMid:27462392
Åhsberg K, Höglund P, Staël von Holstein C. Mortality from peptic ulcer bleeding: The impact of comorbidity and the use of drugs that promote bleeding. Aliment Pharmacol Ther. 2010;32(6):801-10. https://doi.org/10.1111/j.1365-2036.2010.04399.x PMid:20653635
Luo PJ, Lin XH, Lin CC, Luo JC, Hu HY, Ting PH, et al. Risk factors for upper gastrointestinal bleeding among aspirin users: An old issue with new findings from a population-based cohort study. J Formos Med Assoc. 2019;118(5):939-44. https://doi. org/10.1016/j.jfma.2018.10.007 PMid:30366771
Taha AS, Angerson WJ, Knill-Jones RP, Blatchford O. Clinical outcome in upper gastrointestinal bleeding complicating low-dose aspirin and antithrombotic drugs. Aliment Pharmacol Ther. 2006;24(4):633-6. https://doi. org/10.1111/j.1365-2036.2006.03017.x PMid:16907895
Taha A, McCloskey C, CraigenT CC, Angerson W. Antiplatelet versus anticoagulant effects in non-variceal upper gastrointestinal bleeding. Gut. 2019;68(Suppl 2):A1-269. https:// doi.org/10.1016/s0016-5085(19)38792-x
Telaku S, Kraja B, Qirjako G, Prifti S, Fejza H. Clinical outcomes of nonvariceal upper gastrointestinal bleeding in Kosova. Turk J Gastroenterol. 2014;25(Suppl 1):110-5. https://doi.org/10.515
tjg.2014.4351 PMid:25910287
Rubin TA, Murdoch M, Nelson DB. Acute GI bleeding in the setting of supratherapeutic international normalized ratio in patients taking warfarin: Endoscopic diagnosis, clinical management, and outcomes. Gastrointest Endosc. 2003;58(3):369-73. https://doi.org/10.1016/s0016-5107(03)00010-5 PMid:14528210
Wong GL, Wong VW, Chan Y, Ching JY, Au K, Hui AJ, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology. 2009;137(2):525-31. https://doi. org/10.1053/j.gastro.2009.05.006 PMid:19445937
Marmo R, Koch M, Cipolletta L, Capurso L, Pera A, Bianco MA, et al. Predictive factors of mortality from nonvariceal upper gastrointestinal hemorrhage: A multicenter study. Am J Gastroenterol. 2008;103(7):1639-47. PMid:18564127
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