Randomized controlled trial of early endoscopy for upper gastrointestinal bleeding in acute coronary syndrome patients

Chen-Shuan Chung, Chieh-Chang Chen, Kuan-Chih Chen, Yu-Jen Fang, Wen-Feng Hsu, Yen-Nien Chen, Wei-Chuang Tseng, Cheng-Kuan Lin, Tzong-Hsi Lee, Hsiu-Po Wang, Yen-Wen Wu, Chen-Shuan Chung, Chieh-Chang Chen, Kuan-Chih Chen, Yu-Jen Fang, Wen-Feng Hsu, Yen-Nien Chen, Wei-Chuang Tseng, Cheng-Kuan Lin, Tzong-Hsi Lee, Hsiu-Po Wang, Yen-Wen Wu

Abstract

Acute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and 3-day rebleeding rate (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in EE than non-EE group. The mortality, minor and major complication rates were not different between two groups. Male patients were at higher risk of minor and major complications after EE with OR (95% CI) of 3.50 (1.15-10.63) and 4.25 (1.43-12.63), respectively. In multivariate analysis, EE was associated with lower needs for blood transfusion (HR 0.13, 95% CI 0.02-0.98). Among patients who discontinued DAPT during acute UGIB, a higher risk (OR 5.25, 95% CI 1.21-22.74) of coronary artery stent re-thrombosis within 6 months was noticed. EE for acute UGIB in recent ACS patients has higher rate of bleeding control, lower 3-day rebleeding rate and lower needs for blood transfusion, but more complications in male patients. Further enrollment is mandatory to avoid bias from small sample size (ClinicalTrial.gov Number NCT02618980, registration date 02/12/2015).

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
Flow algorithm for enrollment. EE emergent endoscopy, EGD esophagogastroduodenoscopy, ITT intention-to-treat, PP per-protocol, PPI proton pump inhibitor, UGIB upper gastrointestinal bleeding.

References

    1. Hopper AD, Sanders DS. Upper GI bleeding requires prompt investigation. Practitioner. 2011;255(1742):15–19.
    1. Rockall TA, et al. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996;38(3):316–321.
    1. Sung JJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: A randomized trial. Ann. Intern. Med. 2009;150(7):455–464.
    1. Rockall TA, et al. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ. 1995;311(6999):222–226.
    1. Meier PN. Complications in gastrointestinal endoscopy: A summary at the first international symposium in Hannover 2009. Endoscopy. 2011;43(10):892–896.
    1. Blacker DJ, Wijdicks EF, McClelland RL. Stroke risk in anticoagulated patients with atrial fibrillation undergoing endoscopy. Neurology. 2003;61(7):964–968.
    1. Berger JS. Aspirin, clopidogrel, and ticagrelor in acute coronary syndromes. Am. J. Cardiol. 2013;112(5):737–745.
    1. Khan SU, et al. Meta-analysis of the safety and efficacy of the oral anticoagulant agents (apixaban, rivaroxaban, dabigatran) in patients with acute coronary syndrome. Am. J. Cardiol. 2018;121(3):301–307.
    1. Chang SH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250–1259.
    1. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: Meta-analysis. BMJ. 2000;321(7270):1183–1187.
    1. Lin CC, et al. Risk factors of gastrointestinal bleeding in clopidogrel users: A nationwide population-based study. Aliment Pharmacol. Ther. 2013;38(9):1119–1128.
    1. Yeomans D, et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol. Ther. 2005;22(9):795–801.
    1. Dorreen A, et al. Safety of digestive endoscopy following acute coronary syndrome: A systematic review. Can. J. Gastroenterol. Hepatol. 2016;2016:9564529. doi: 10.1155/2016/9564529.
    1. ErtlT G, Frantz S. Healing after myocardial infarction. Cardiovasc. Res. 2005;66:22–32.
    1. Gaudron P, et al. Time course of cardiac structural, functional and electrical changes in asymptomatic patients after myocardial infarction: Their inter-relation and prognostic impact. J. Am. Coll. Cardiol. 2001;38(1):33–40.
    1. National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am. J. Kidney Dis. 2002;39(2 Suppl 1):S1–S266.
    1. Lau JY, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N. Engl. J. Med. 2007;356(16):1631–1640.
    1. Knaus WA, et al. APACHE II: A severity of disease classification system. Crit. Care Med. 1985;13(10):818–829.
    1. Laine L, Peterson WL. Bleeding peptic ulcer. N. Engl. J. Med. 1994;331:717–727.
    1. Van DJ, Brugge WR. Endoscopy of the upper gastrointestinal tract. N. Engl. J. Med. 1999;341(23):1738–1748.
    1. Chen YL, et al. Major adverse upper gastrointestinal events in patients with ST-segment elevation myocardial infarction undergoing primary coronary intervention and dual antiplatelet therapy. Am. J. Cardiol. 2011;108(12):1704–1709.
    1. Shalev A, et al. Incidence, predictors and outcome of upper gastrointestinal bleeding in patients with acute coronary syndromes. Int. J. Cardiol. 2012;157(3):386–390.
    1. Yusuf S, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med. 2001;345(7):494–502.
    1. Nikolsky E, et al. Gastrointestinal bleeding in patients with acute coronary syndromes: Incidence, predictors, and clinical implications: Analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J. Am. Coll. Cardiol. 2009;54(14):1293–1302.
    1. Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet. 2000;356(9238):1318–1321.
    1. Weisman SM, Graham DY. Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch. Intern. Med. 2002;162(19):2197–2202.
    1. AT Collaboration Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7328):71–86.
    1. Chowdhury A, et al. Gastro-duodenal mucosal changes associated with low-dose aspirin therapy: A prospective, endoscopic study. Indian J. Gastroenterol. 2001;20(6):227–229.
    1. CS Committee A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348(9038):1329–1339.
    1. Ma L, 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(11):6470–6475.
    1. Chan FK, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N. Engl. J. Med. 2005;352(3):238–244.
    1. Ng FH, et al. High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease. Aliment Pharmacol. Ther. 2003;18(4):443–449.
    1. Al-Ebrahim F, et al. Safety of esophagogastroduodenoscopy within 30 days of myocardial infarction: A retrospective cohort study from a Canadian tertiary centre. Can. J. Gastroenterol. 2012;26(3):151–154.
    1. Cappell MS. The safety and clinical utility of esophagogastroduodenoscopy for acute gastrointestinal bleeding after myocardial infarction: A six-year study of 42 endoscopies in 34 consecutive patients at two university teaching hospitals. Am. J. Gastroenterol. 1993;88(3):344–350.
    1. Cappell MS, Iacovone FMJ. Safety and efficacy of esophagogastroduodenoscopy after myocardial infarction. Am. J. Med. 1999;106(1):29–35.
    1. Lee JG, Krucoff MW, Brazer SR. Periprocedural myocardial ischemia in patients with severe symptomatic coronary artery disease undergoing endoscopy: Prevalence and risk factors. Am. J. Med. 1995;99(3):270–275.
    1. Lim RG, et al. Endoscopy after acute myocardial infarction: An evaluation of safety. South Med. J. 2013;106(10):545–549.
    1. Spier BJ, et al. Safety of endoscopy after myocardial infarction based on cardiovascular risk categories: A retrospective analysis of 135 patients at a tertiary referral medical center. J. Clin. Gastroenterol. 2007;41(5):462–467.
    1. Cena M, et al. Safety of endoscopic procedures after acute myocardial infarction: A systematic review. Cardiol. J. 2012;19(5):447–452.
    1. Hoffman GR, et al. Safety of endoscopy for hospitalized patients with acute myocardial infarction: A national analysis. Am. J. Gastroenterol. 2020;115(3):376–800.
    1. Collet JP, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Rev. Esp. Cardiol. (Engl Ed) 2021;74(6):544.
    1. Kumbhani DJ, 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. 2021;77(5):629–658.

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