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Published in: BMC Cardiovascular Disorders 1/2016

Open Access 01-12-2016 | Research article

Risk of bleeding after hospitalization for a serious coronary event: a retrospective cohort study with nested case-control analyses

Authors: Antonio González-Pérez, María E. Sáez, Saga Johansson, Anders Himmelmann, Luis A. García Rodríguez

Published in: BMC Cardiovascular Disorders | Issue 1/2016

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Abstract

Background

Bleeding events have been associated with the use of antiplatelet agents. This study estimated the incidence of bleeding events in patients previously hospitalized for a serious coronary event and determined the risks of bleeding associated with the use of acetylsalicylic acid (ASA) and/or clopidogrel.

Methods

A UK primary care database was used to identify 27,707 patients aged 50 to 84 years, hospitalized for a serious coronary event during 2000 to 2007 and who were alive 30 days later (start date). Patients were followed up until they reached an endpoint (hemorrhagic stroke, upper or lower gastrointestinal bleeding [UGIB/LGIB]), death or end of study [June 30, 2011]) or met an exclusion criterion. Risk factors for bleeding were determined in a nested case-control analysis.

Results

Incidences of hemorrhagic stroke, UGIB, and LGIB were 5.0, 11.9, and 25.5 events per 10,000 person-years, respectively, and increased with age. UGIB and LGIB led to hospitalization in 73 and 23 % of patients, respectively. Non-users of ASA, who were mostly discontinuers, and current users of ASA had similar risks of hemorrhagic stroke, UGIB, and LGIB. Users of combined antithrombotic therapy (warfarin and antiplatelets) experienced an increased risk of hemorrhagic stroke (odds ratio [OR], 6.36; 95 % confidence interval [CI], 1.34–30.16), whereas users of combined antiplatelet therapy (clopidogrel and ASA) experienced an increased risk of UGIB (OR, 2.42; 95 % CI, 1.09–5.36). An increased risk of LGIB (OR, 1.86; 95 % CI, 1.34–2.57) was also observed in users of clopidogrel.

Conclusions

In patients previously hospitalized for a serious coronary event, combined antithrombotic therapy was associated with an increased risk of hemorrhagic stroke, whereas combined antiplatelet therapy was associated with an increased risk of UGIB.Non-use of ASA was rare in this population and use of ASA was not associated with a significantly increased risk of hemorrhagic stroke, UGIB, or LGIB.
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Literature
2.
go back to reference 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;32:2999–3054.CrossRefPubMed 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;32:2999–3054.CrossRefPubMed
3.
go back to reference Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the European society of cardiology (ESC). Eur Heart J. 2012;33:2569–619.CrossRefPubMed Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the European society of cardiology (ESC). Eur Heart J. 2012;33:2569–619.CrossRefPubMed
4.
go back to reference Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European society of cardiology (ESC) and the European association for cardio-thoracic surgery (EACTS). developed with the special contribution of the European association of percutaneous cardiovascular interventions (EAPCI). Eur Heart J. 2014;35:2541–619.CrossRefPubMed Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European society of cardiology (ESC) and the European association for cardio-thoracic surgery (EACTS). developed with the special contribution of the European association of percutaneous cardiovascular interventions (EAPCI). Eur Heart J. 2014;35:2541–619.CrossRefPubMed
5.
go back to reference Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–60.CrossRefPubMed Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–60.CrossRefPubMed
6.
go back to reference Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. 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.CrossRefPubMed Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. 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.CrossRefPubMed
7.
go back to reference Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.CrossRefPubMed Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.CrossRefPubMed
8.
go back to reference Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.CrossRefPubMed Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.CrossRefPubMed
9.
go back to reference Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, et al. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607–21.CrossRefPubMed Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, et al. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607–21.CrossRefPubMed
10.
go back to reference Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. 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;118:1894–909.CrossRefPubMed Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. 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;118:1894–909.CrossRefPubMed
11.
go back to reference García Rodríguez LA, Lin KJ, Hernández-Díaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123:1108–15.CrossRefPubMed García Rodríguez LA, Lin KJ, Hernández-Díaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123:1108–15.CrossRefPubMed
12.
13.
go back to reference Casado Arroyo R, Polo-Tomas M, Roncales MP, Scheiman J, Lanas A. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart. 2012;98:718–23.CrossRefPubMed Casado Arroyo R, Polo-Tomas M, Roncales MP, Scheiman J, Lanas A. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart. 2012;98:718–23.CrossRefPubMed
14.
go back to reference Hashash JG, Shamseddeen W, Skoury A, Aoun N, Barada K. Gross lower gastrointestinal bleeding in patients on anticoagulant and/or antiplatelet therapy: endoscopic findings, management, and clinical outcomes. J Clin Gastroenterol. 2009;43:36–42.CrossRefPubMed Hashash JG, Shamseddeen W, Skoury A, Aoun N, Barada K. Gross lower gastrointestinal bleeding in patients on anticoagulant and/or antiplatelet therapy: endoscopic findings, management, and clinical outcomes. J Clin Gastroenterol. 2009;43:36–42.CrossRefPubMed
15.
go back to reference Nagata N, Niikura R, Aoki T, Shimbo T, Kishida Y, Sekine K, et al. Lower GI bleeding risk of nonsteroidal anti-inflammatory drugs and antiplatelet drug use alone and the effect of combined therapy. Gastrointest Endosc. 2014;80:1124–31.CrossRefPubMed Nagata N, Niikura R, Aoki T, Shimbo T, Kishida Y, Sekine K, et al. Lower GI bleeding risk of nonsteroidal anti-inflammatory drugs and antiplatelet drug use alone and the effect of combined therapy. Gastrointest Endosc. 2014;80:1124–31.CrossRefPubMed
16.
go back to reference Abraham NS, Hartman C, Richardson P, Castillo D, Street Jr RL, Naik AD. Risk of lower and upper gastrointestinal bleeding, transfusions, and hospitalizations with complex antithrombotic therapy in elderly patients. Circulation. 2013;128:1869–77.CrossRefPubMed Abraham NS, Hartman C, Richardson P, Castillo D, Street Jr RL, Naik AD. Risk of lower and upper gastrointestinal bleeding, transfusions, and hospitalizations with complex antithrombotic therapy in elderly patients. Circulation. 2013;128:1869–77.CrossRefPubMed
18.
go back to reference Bourke A, Dattani H, Robinson M. Feasibility study and methodology to create a quality-evaluated database of primary care data. Inform Prim Care. 2004;12:171–7.PubMed Bourke A, Dattani H, Robinson M. Feasibility study and methodology to create a quality-evaluated database of primary care data. Inform Prim Care. 2004;12:171–7.PubMed
19.
go back to reference O’Neil M, Payne C, Read J. Read Codes Version 3: a user led terminology. Methods Inf Med. 1995;34:187–92.PubMed O’Neil M, Payne C, Read J. Read Codes Version 3: a user led terminology. Methods Inf Med. 1995;34:187–92.PubMed
21.
go back to reference Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2007;16:393–401.CrossRefPubMed Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2007;16:393–401.CrossRefPubMed
22.
go back to reference García Rodríguez LA, Johansson S, Cea SL. Use of clopidogrel and proton pump inhibitors after a serious acute coronary event: risk of coronary events and peptic ulcer bleeding. Thromb Haemost. 2013;110:1014–24.CrossRefPubMed García Rodríguez LA, Johansson S, Cea SL. Use of clopidogrel and proton pump inhibitors after a serious acute coronary event: risk of coronary events and peptic ulcer bleeding. Thromb Haemost. 2013;110:1014–24.CrossRefPubMed
23.
go back to reference Gaist D, Wallander MA, González-Pérez A, García Rodríguez LA. Incidence of hemorrhagic stroke in the general population: validation of data from the health improvement network. Pharmacoepidemiol Drug Saf. 2013;22:176–82.CrossRefPubMed Gaist D, Wallander MA, González-Pérez A, García Rodríguez LA. Incidence of hemorrhagic stroke in the general population: validation of data from the health improvement network. Pharmacoepidemiol Drug Saf. 2013;22:176–82.CrossRefPubMed
24.
go back to reference García Rodríguez LA, Barreales TL. Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology. 2007;132:498–506.CrossRefPubMed García Rodríguez LA, Barreales TL. Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology. 2007;132:498–506.CrossRefPubMed
25.
go back to reference Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. 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;364:331–7.CrossRefPubMed Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. 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;364:331–7.CrossRefPubMed
26.
go back to reference Lin CC, Hu HY, Luo JC, Peng YL, Hou MC, Lin HC, et al. Risk factors of gastrointestinal bleeding in clopidogrel users: a nationwide population-based study. Aliment Pharmacol Ther. 2013;38:1119–28.CrossRef Lin CC, Hu HY, Luo JC, Peng YL, Hou MC, Lin HC, et al. Risk factors of gastrointestinal bleeding in clopidogrel users: a nationwide population-based study. Aliment Pharmacol Ther. 2013;38:1119–28.CrossRef
27.
go back to reference McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119:624–38.CrossRefPubMed McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119:624–38.CrossRefPubMed
28.
go back to reference Valkhoff VE, Sturkenboom M, Hill C, Veldhuyzen van Zanten S, Kuipers EJ. Low-dose acetylsalicylic acid use and the risk of upper gastrointestinal bleeding: a meta-analysis of randomized clinical trials and observational studies. Can J Gastroenterol. 2013;27:159–67.CrossRefPubMedPubMedCentral Valkhoff VE, Sturkenboom M, Hill C, Veldhuyzen van Zanten S, Kuipers EJ. Low-dose acetylsalicylic acid use and the risk of upper gastrointestinal bleeding: a meta-analysis of randomized clinical trials and observational studies. Can J Gastroenterol. 2013;27:159–67.CrossRefPubMedPubMedCentral
29.
go back to reference García Rodríguez LA, Gaist D, Morton J, Cookson C, González-Pérez A. Antithrombotic drugs and risk of hemorrhagic stroke in the general population. Neurology. 2013;81:566–74.CrossRefPubMed García Rodríguez LA, Gaist D, Morton J, Cookson C, González-Pérez A. Antithrombotic drugs and risk of hemorrhagic stroke in the general population. Neurology. 2013;81:566–74.CrossRefPubMed
30.
go back to reference D’Ascenzo F, Taha S, Moretti C, Omede P, Grossomarra W, et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2015;115:1185–93.CrossRefPubMed D’Ascenzo F, Taha S, Moretti C, Omede P, Grossomarra W, et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2015;115:1185–93.CrossRefPubMed
31.
go back to reference Lanas A, Carrera-Lasfuentes P, Arguedas Y, Garcia S, Bujanda L, Calvet X, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13:906–12.CrossRefPubMed Lanas A, Carrera-Lasfuentes P, Arguedas Y, Garcia S, Bujanda L, Calvet X, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13:906–12.CrossRefPubMed
32.
go back to reference Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769–79.CrossRefPubMed Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769–79.CrossRefPubMed
Metadata
Title
Risk of bleeding after hospitalization for a serious coronary event: a retrospective cohort study with nested case-control analyses
Authors
Antonio González-Pérez
María E. Sáez
Saga Johansson
Anders Himmelmann
Luis A. García Rodríguez
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2016
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-016-0348-6

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