Incidence, associated outcomes, and predictors of upper gastrointestinal bleeding following acute myocardial infarction: a SWEDEHEART-based nationwide cohort study

Philip Sarajlic, Moa Simonsson, Tomas Jernberg, Magnus Bäck, Robin Hofmann, Philip Sarajlic, Moa Simonsson, Tomas Jernberg, Magnus Bäck, Robin Hofmann

Abstract

Aims: Of all spontaneous bleeding complications in patients with acute myocardial infarction (MI), upper gastrointestinal bleeding (UGIB) is common and of specific interest since it could be prevented by several prophylactic measures. We aimed to determine the incidence, associated outcomes, and predictors of UGIB following acute MI.

Methods and results: All patients with acute MI enrolled in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry from January 2007 to June 2016 and discharged alive on any antithrombotic therapy (n = 149 477) were followed regarding UGIB for 1 year. Associated outcomes were determined by Cox proportional hazards regression with UGIB as a time-dependent covariate, adjusting for baseline characteristics, invasive treatment, and medical treatment at discharge. Predictors of UGIB were determined by logistic regression and machine learning models.At 1 year, UGIB had occurred in 2230 patients (cumulative incidence 1.5%) and was significantly associated with an increased risk of all-cause death [hazard ratio (HR) 2.86, 95% confidence interval (CI) 2.58-3.16] and stroke (HR 1.80, 95% CI 1.32-2.45) but not with recurrent MI (HR 1.17, 95% CI 0.97-1.42). The most important predictors of UGIB were haemoglobin, age, systolic blood pressure, blood glucose, smoking status, previous upper gastrointestinal bleeding, and antithrombotic and gastroprotective treatment.

Conclusion: After acute MI, readmission because of UGIB is common and significantly associated with poor prognosis. By using machine learning in addition to traditional logistic regression, new predictors of UGIB, such as blood glucose and smoking status, were identified.

Keywords: Acute myocardial infarction; Predictors; Registry; Upper gastrointestinal bleeding.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Graphical Abstract
Graphical Abstract
Incidence, predictors, and associated outcomes following acute myocardial infarction.
Figure 1
Figure 1
Unadjusted incidence of major adverse cardiovascular events (defined as composite of myocardial infarction, stroke, and all-cause death) in patients with or without upper gastrointestinal bleeding using upper gastrointestinal bleeding as a time-dependent event.
Figure 2
Figure 2
The most important predictors in the best-performing machine learning model, the random forest. For each of the 10 variables, a variable importance weight measure is presented, which is proportional to the increase in the misclassification rate of the random forest, if the variable was removed from the model. Higher importance weights indicate that the variable is more important when predicting upper gastrointestinal bleeding events.
Figure 3
Figure 3
The most important continuous predictors in the logistic regression model. Estimated spline transformation in relation to log odds of upper gastrointestinal bleeding.

References

    1. Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group; ESC Committee for Practice Guidelines; 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(3):213–260.
    1. Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Juni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM; ESC Scientific Document Group . 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2020;41:3495–3497.
    1. Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KA, Yusuf S. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006;114(8):774–782.
    1. Buccheri S, Capodanno D, James S, Angiolillo DJ. Bleeding after antiplatelet therapy for the treatment of acute coronary syndromes: a review of the evidence and evolving paradigms. Expert Opin Drug Saf 2019:1–19.
    1. Magnani G, Ardissino D, Im K, Budaj A, Storey RF, Steg PG, Bhatt DL, Cohen M, Oude Ophius T, Goudev A, Parkhomenko A, Kamensky G, Angiolillo DJ, Lopez-Sendon J, Johanson P, Braunwald E, Sabatine MS, Bonaca MP. Predictors, type, and impact of bleeding on the net clinical benefit of long-term ticagrelor in stable patients with prior myocardial infarction. J Am Heart Assoc 2021;10(4):e017008.
    1. Sehested TSG, Carlson N, Hansen PW, Gerds TA, Charlot MG, Torp-Pedersen C, Kober L, Gislason GH, Hlatky MA, Fosbol EL. Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction. Eur Heart J 2019;40(24):1963–1970.
    1. Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, Shook TL, Lapuerta P, Goldsmith MA, Laine L, Scirica BM, Murphy SA, Cannon CP; COGENT Investigators . Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010;363(20):1909–1917.
    1. Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Dzavik V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med 2019;381(21):2032–2042.
    1. Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, Cho JY, Her AY, Cho S, Jeon DW, Yoo SY, Cho DK, Hong BK, Kwon H, Ahn CM, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Hong MK, Jang Y; TICO Investigators . Effect of ticagrelor monotherapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute coronary syndrome: the TICO randomized clinical trial. JAMA 2020;323(23):2407–2416.
    1. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol 2017;112(2):212–239.
    1. Kikkert WJ, Hassell M, Delewi R, van der Laan MH, Baan J Jr, Vis MM, Koch KT, de Winter RJ, Piek JJ, Tijssen JGP, Henriques JPS. Predictors and prognostic consequence of gastrointestinal bleeding in patients with ST-segment elevation myocardial infarction. Int J Cardiol 2015;184:128–134.
    1. Nikolsky E, Stone GW, Kirtane AJ, Dangas GD, Lansky AJ, McLaurin B, Lincoff AM, Feit F, Moses JW, Fahy M, Manoukian SV, White HD, Ohman EM, Bertrand ME, Cox DA, Mehran R. 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. Jernberg T, Attebring MF, Hambraeus K, Ivert T, James S, Jeppsson A, Lagerqvist B, Lindahl B, Stenestrand U, Wallentin L. The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Heart 2010;96(20):1617–1621.
    1. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, Heurgren M, Olausson PO. External review and validation of the Swedish National Inpatient Register. BMC Public Health 2011;11:450.
    1. Sarajlic P, Plunde O, Franco-Cereceda A, Back M. Artificial intelligence models reveal sex-specific gene expression in aortic valve calcification. JACC Basic Transl Sci 2021;6(5):403–412.
    1. Simonsson M, Wallentin L, Alfredsson J, Erlinge D, Hellstrom Angerud K, Hofmann R, Kellerth T, Lindhagen L, Ravn-Fischer A, Szummer K, Ueda P, Yndigegn T, Jernberg T. Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry. Eur Heart J 2020;41(7):833–843.
    1. Bilal M, Samuel R, Khalil MK, Singh S, Parupudi S, Abougergi MS. Nonvariceal upper GI hemorrhage after percutaneous coronary intervention for acute myocardial infarction: a national analysis over 11 months. Gastrointest Endosc 2020;92(1):65–74.e2.
    1. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. 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(9921):955–962.
    1. Koskinas KC, Raber L, Zanchin T, Wenaweser P, Stortecky S, Moschovitis A, Khattab AA, Pilgrim T, Blochlinger S, Moro C, Juni P, Meier B, Heg D, Windecker S. Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions. Circ Cardiovasc Interv 2015;8(5):e002053.
    1. Doyle BJ, Rihal CS, Gastineau DA, Holmes DR Jr. Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol 2009;53(22):2019–2027.
    1. Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, Wang TY, Gibler WB, Ohman EM, Roe MT, Pollack CV Jr, Peterson ED, Alexander KP. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) bleeding score. Circulation 2009;119(14):1873–1882.
    1. Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, Spertus JA, Steg PG, Cutlip DE, Rinaldi MJ, Camenzind E, Wijns W, Apruzzese PK, Song Y, Massaro JM, Mauri L; DAPT Study Investigators . Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA 2016;315(16):1735–1749.
    1. Ozaydin N, Turkyilmaz SA, Cali S. Prevalence and risk factors of Helicobacter pylori in Turkey: a nationally-representative, cross-sectional, screening with the 13C-urea breath test. BMC Public Health 2013;13:1215.
    1. Valgimigli M, Costa F, Lokhnygina Y, Clare RM, Wallentin L, Moliterno DJ, Armstrong PW, White HD, Held C, Aylward PE, Van de Werf F, Harrington RA, Mahaffey KW, Tricoci P. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur Heart J 2017;38(11):804–810.
    1. Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, Pilgrim T, Hong MK, Kim HS, Colombo A, Steg PG, Zanchin T, Palmerini T, Wallentin L, Bhatt DL, Stone GW, Windecker S, Steyerberg EW, Valgimigli M; PRECISE-DAPT Study Investigators . Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017;389(10073):1025–1034.
    1. Raposeiras-Roubin S, Faxen J, Iniguez-Romo A, Henriques JPS, D'Ascenzo F, Saucedo J, Szummer K, Jernberg T, James SK, Juanatey JRG, Wilton SB, Kikkert WJ, Nunez-Gil I, Ariza-Sole A, Song X, Alexopoulos D, Liebetrau C, Kawaji T, Moretti C, Huczek Z, Nie SP, Fujii T, Correia L, Kawashiri MA, Caneiro-Queija B, Cobas-Paz R, Acuna JMG, Southern D, Alfonso E, Terol B, Garay A, Zhang D, Chen Y, Xanthopoulou I, Osman N, Mollmann H, Shiomi H, Giordana F, Gaita F, Kowara M, Filipiak K, Wang X, Yan Y, Fan JY, Ikari Y, Nakahayshi T, Sakata K, Yamagishi M, Kalpak O, Kedev S, Rivera-Asenjo D, Abu-Assi E. Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: the BleeMACS score. Int J Cardiol 2018;254:10–15.
    1. Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, Farb A, Gibson CM, Gregson J, Haude M, James SK, Kim HS, Kimura T, Konishi A, Laschinger J, Leon MB, Magee PFA, Mitsutake Y, Mylotte D, Pocock S, Price MJ, Rao SV, Spitzer E, Stockbridge N, Valgimigli M, Varenne O, Windhoevel U, Yeh RW, Krucoff MW, Morice MC. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J 2019;40(31):2632–2653.
    1. Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Hadamitzky M, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Holdt L, Felix SB, Parma R, Klopotowski M, Schwinger RHG, Rieber J, Huber K, Neumann FJ, Koltowski L, Mehilli J, Huczek Z, Massberg S; TROPICAL-ACS Investigators . Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet 2017;390(10104):1747–1757.
    1. Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res 2003;110(5–6):255–258.
    1. Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus Panel . Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut 2017;66(1):6–30.
    1. Hoedemaker NPG, Damman P, Ottervanger JP, Dambrink JHE, Gosselink ATM, Kedhi E, Kolkman E, de Winter RJ, van't Hof AWJ. Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry. Eur Heart J Cardiovasc Pharmacother 2019;5(3):127–138.

Source: PubMed

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