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Position papers and consensus documents from the ESC Working Group on Thrombosis

Role and analysis of monocyte subsets in cardiovascular disease

Joint consensus document of the European Society of Cardiology (ESC) Working Groups “Atherosclerosis & Vascular Biology” and “Thrombosis”

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Authors: C. Weber, E. Shantsila, M. Hristov, G. Caligiuri, T. Guzik, G. H. Heine, I. E. Hoefer, C. Monaco, K. Peter, E. Rainger, A. Siegbahn, S. Steffens, J. Wojta, G. Y. H. Lip

References: Thrombosis and Haemostasis; 0340-6245; doi:10.1160/TH16-02-0091; Ahead of Print: 2016-07-14

Summary: Monocytes as cells of the innate immunity are prominently involved in the development of atherosclerotic lesions. The heterogeneity of blood monocytes has widely been acknowledged by accumulating experimental and clinical data suggesting a differential, subset-specific contribution of the corresponding subpopulations to the pathology of cardiovascular and other diseases. This document re-evaluates current nomenclature and summarises key findings on monocyte subset biology to propose a consensus statement about phenotype, separation and quantification of the individual subsets.

Antithrombotic therapy in the elderly

Expert position paper of the European Society of Cardiology Working Group on Thrombosis

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Authors: Felicita Andreotti, Bianca Rocca, Steen Husted, Ramzi A. Ajjan, Jurrien ten Berg, Marco Cattaneo, Jean-Philippe Collet, Raffaele De Caterina, Keith A.A. Fox, Sigrun Halvorsen, Kurt Huber, Elaine M. Hylek, Gregory Y.H. Lip, Gilles Montalescot, Joao Morais, Carlo Patrono, Freek W.A. Verheugt, Lars Wallentin, Thomas W. Weiss, Robert F. Storey on behalf of the ESC Thrombosis Working Group

Eur Heart J (2015) ; DOI: ; First published online: 10 July 2015

Contemporary medicine is shifting towards person rather than disease-oriented care.1 With increasing life expectancy and the ageing of baby boomers, the proportion over 60 years is growing faster than the overall population, with worldwide estimates reaching 2 billion by 2050 ( In parallel, acute coronary syndromes (ACS) and atrial fibrillation (AF)—the most frequent indications for dual platelet inhibition or anticoagulation—occur mostly in older patients.2–6 There is general agreement that people ≥75 years can be defined ‘elderly’; however, cutoffs as low as 65 years have been applied to important clinical datasets and risk scores.3,7–10 Moreover, ageing is a continuous process and life-span expansion is deflating ( For these reasons, a threshold to define ‘elderly’ has been intentionally avoided in this document. Of note, over one third of patients admitted with acute myocardial infarction (MI) and two thirds dying from MI are over 75 years, but <7% of patients in ACS trials are reported ≥75 years.11 Older patients have multi-organ changes, increased risk of both bleeding and ischaemic events,3,5,12 frequent comorbidities/comedication, and reduced adherence to prescriptions. Given the challenges of antithrombotic treatment in the elderly, the European Society of Cardiology (ESC) Working Group on Thrombosis gathered a task group to address the topic.

Antithrombotic management in patients undergoing electrophysiological procedures

A European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS)

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Authors: Christian Sticherling (Chair; Switzerland), Francisco Marin (Co-chair; Spain), David Birnie (Canada), Giuseppe Boriani (Italy), Hugh Calkins (USA), Gheorghe-Andrei Dan (Romania), Michele Gulizia (Italy), Sigrun Halvorsen (Norway), Gerhard Hindricks (Germany), Karl-Heinz Kuck (Germany), Angel Moya (Spain), Tatjana Potpara (Serbia), Vanessa Roldan (Spain), Roland Tilz (Germany), and Gregory Y.H. Lip (UK)

Document reviewers: Bulent Gorenek (Reviewer Coordinator;Turkey), Julia H. Indik (USA), Paulus Kirchhof (UK), Chang-Shen Ma (China), Calambur Narasimhan (India), Jonathan Piccini (USA), Andrea Sarkozy (Belgium), Dipen Shah (Switzerland), and Irene Savelieva (on behalf of EP-Europace, UK)

Europace (2015) 17, 1197–1214 ; doi:10.1093/europace/euv190 ; First published online: 23 June 2015

Introduction: Since the advent of the non-vitamin K antagonist oral anticoagulant (NOAC) agents, which act as direct thrombin inhibitors or inhibitors of Factor Xa, clinicians are provided with valuable alternatives to vitamin K antagonists (VKAs). At the same time, electrophysiologists frequently perform more invasive procedures, increasingly involving the left chambers of the heart. Thus, they are constantly faced with the dilemma of balancing the risk for thromboembolic events and bleeding complications. These changes in the rapidly evolving field mandate an update of the European Heart Rhythm Association (EHRA) 2008 consensus document on this topic(1). The present document covers the antithrombotic management during different ablation procedures, implantation or exchange of cardiac implantable electronical devices (CIEDs), as wellasthe management of peri-interventional bleeding complications.
The document is not aformal guideline and due to the lackof prospectiverandomized controlled trials (RCTs) for manyof the clinical situations encountered, the recommendations are often ‘expert opinion’. The document strives to be practical for which reason we subdivided it in the three main topics: ablation procedure, CIED implantation or generator change, and issues of peri-interventional bleeding complications on concurrent antiplatelet therapy. For quick reference, every subchapter is followed by a short section on consensus recommendations.
Many RCTs are ongoing in this field and it is hoped that this document will help to prompt further well-designed studies.

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions

A joint consensus document with EHRA, EAPCI) and ACCA endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)

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Authors: Task Force Members, Gregory Y.H. Lip, Stephan Windecker, Kurt Huber, Paulus Kirchhof, Francisco Marin,  Jurriën M. Ten Berg, Karl Georg Haeusler, Giuseppe Boriani,Davide Capodanno, Martine Gilard, Uwe Zeymer and Deirdre Lane

Eur Heart J (2014) doi: 10.1093/eurheartj/ehu298 First published online: August 25, 2014

Atrial fibrillation (AF) confers a substantial risk of mortality and morbidity from stroke and thrombo-embolism, and this common cardiac arrhythmia represents a major healthcare burden in Europe.1 Stroke prevention is central to the management of AF patients, with the 2012 focused update of the European Society of Cardiology (ESC) guidelines2 recommending oral anticoagulation (OAC) using well-controlled adjusted dose vitamin K antagonists (VKAs, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, previously referred to as new or novel OACs3) for patients with AF and ≥1 stroke risk factor(s). Also, these guidelines strongly advocate a clinical practice shift so that the initial decision step now is the identification of ‘truly low risk’ patients, essentially those aged <65 years without any stroke risk factor (both male and female), who do not need any antithrombotic therapy.2 The ESC guidelines also recommend the use of the CHA2DS2-VASc score4 for stroke risk assessment, and define ‘low-risk’ patients as those with a CHA2DS2-VASc score = 0 (males) or score = 1 (females). Subsequent to this initial step of identifying the low-risk patients, effective stroke prevention (which is essentially OAC) can then be offered to AF patients with ≥1 stroke risk factor(s), with treatment decisions made in consultation with patients and incorporating their preferences...

Aspirin Therapy in Primary Cardiovascular Disease Prevention

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Authors: Sigrun Halvorsen, Felicita Andreotti, Jurriën M. ten Berg, Marco Cattaneo, Sergio Coccheri, Roberto Marchioli, João Morais, Freek W.A. Verheugt, Raffaele De Caterina

J Am Coll Cardiol. 2014;64(3):319-327. doi:10.1016/j.jacc.2014.03.049; Volume 64, Issue 3, July 2014

Although the use of oral anticoagulants (vitamin K antagonists) has been abandoned in primary cardiovascular prevention due to lack of a favorable benefit-to-risk ratio, the indications for aspirin use in this setting continue to be a source of major debate, with major international guidelines providing conflicting recommendations. Here, we review the evidence in favor and against aspirin therapy in primary prevention based on the evidence accumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, we argue for a pragmatic approach to using low-dose aspirin in primary cardiovascular prevention and suggest its use in patients at high cardiovascular risk, defined as $2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding. (J Am Coll Cardiol 2014;64:319–27) © 2014 by the American College of Cardiology Foundation.

Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery

Joint paper with the WG on Cardiovascular Surgery

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Authors: Miguel Sousa-Uva, Robert Storey, Kurt Huber, Volkmar Falk, Adeline Leite-Moreira, Julien Amour, Nawwar Al- Attar, Raimondo Ascione, David Taggart , and Jean-Philippe Collet

Eur Heart J (2014); doi: 10.1093/eurheartj/ehu158; First published online: April 18, 2014

Coronary artery bypass grafting (CABG)-related bleeding complications and perioperative coronary events are strongly influenced by the management of antithrombotic therapy before and after CABG. Bleeding but also blood products transfusion increase the risk of death and compromise the long-term benefits of CABG.1 The use of new P2Y12 inhibitors, increasing pre-CABG percutaneous coronary interventions (PCI) with drug eluting stents (DES) requiring specific antiplatelet regimens, and advances in surgical technique has prompted the ESC Working Group on Cardiovascular Surgery and the ESC Working Group on Thrombosis to review the evidence of peri-CABG recommendations on antithrombotic management. Due to the paucity of randomized trials, most of the evidence is still derived from observational studies and expert consensus, further reinforcing the importance of a multidisciplinary consultation for optimal decision making.

Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy

Joint paper with the WG on Cardiovascular Pharmacology & Drug Therapy 

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Authors : Stefan Agewall1, Cattaneo, J.P. Collet, F. Andreotti, G.Y.H. Lip,F.W.A. Verheugt, K. Huber, E.L. Grove, J. Morais, S. Husted, S. Wassmann, G. Rosano, D. Atar1, A. Pathak, K. Kjeldsen, and R.F. Storey

Eur Heart J (2013) doi: 10.1093/eurheartj/eht042 First published online: February 20, 2013

The ESC NSTEMI and STEMI guidelines1,2 and an ACCF/ACG/AHA consensus document3 recommend treatment with proton pump inhibitors (PPIs) in patients treated with dual antiplatelet treatment (DAPT) during the initial phase of an acute coronary syndrome (ACS) (ESC Class 1A recommendation), particularly in patients with a history of GI bleeding or peptic ulcer. Several studies have raised concerns that many PPIs, especially omeprazole, might diminish the antiplatelet effects of clopidogrel, most likely through inhibition of CYP2C19 and, consequently, the conversion of clopidogrel into its active metabolite.

The aim of this position paper is to review the pharmacokinetic background of the interactions between these drugs, and their consequences on clinical outcomes, and to present suggestions for management of this important issue.

Several agents widely used in patients on acetylsalicylic acid (ASA) may interact with the antiplatelet effects of ASA, but none through the CYP2C9 pathway by which ASA is metabolized. Recently, it has been reported that concomitant use of PPIs reduces the protective efficacy of ASA in patients with ischaemic heart disease.6,7 A case–control study investigated the antiplatelet effect of ASA in 418 ASA-treated CVD patients, 54 of whom were also treated with PPIs.7 Patients receiving PPIs had reduced antiplatelet effect of ASA, as shown by greater residual platelet aggregation responses. However, interaction between PPI and ASA is controversial.8 Potential clinical implications of these findings were explored by a registry study in a large population of ASA-treated patients with first time myocardial infarction.6 Even after adjusting for baseline variables with multivariate analysis and propensity score matching, PPI use was still significantly associated with …

General mechanisms of coagulation and targets of anticoagulants (Section I)

Position Paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease

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Authors : Raffaele De Caterina; Steen Husted; Lars Wallentin; Felicita Andreotti; Harald Arnesen; Fedor Bachmann; Colin Baigent; Kurt Huber; Jørgen Jespersen; Steen Dalby Kristensen; Gregory Y. H. Lip; João Morais; Lars Hvilsted Rasmussen; Agneta Siegbahn; Freek W. A. Verheugt; Jeffrey I. Weitz

doi:10.1160/TH12-10-0772; Thromb Haemost 2013; 109: 569–579

Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and selfinhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. “Classical” anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.

Parenteral anticoagulants in heart disease: Current status and perspectives (Section II)

Position Paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease

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Authors : Raffaele De Caterina; Steen Husted; Lars Wallentin; Felicita Andreotti; Harald Arnesen; Fedor Bachmann; Colin Baigent; Kurt Huber; Jørgen Jespersen; Steen Dalby Kristensen; Gregory Y. H. Lip

doi:10.1160/TH12-06-0403; Thromb Haemost 2013; 109: 769–786

Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair.
Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes

A position paper from the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease

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Coordinating Committee: Raffaele De Caterina, Steen Husted, Lars Wallentin

Task Force Members: Raffaele De Caterina, Steen Husted, Lars Wallentin, Felicita Andreotti, Harald Arnesen, Fedor Bachmann, Colin Baigent, Kurt Huber, Jørgen Jespersen, Steen Dalby Kristensen, Gregory Y. H. Lip,João Morais, Lars Hvilsted Rasmussen, Agneta Siegbahn, Freek W. A. Verheugt, Jeffrey I. Weitz

Journal: Journal of the American College of Cardiology; Issue: Vol. 59, No. 16, 2012; doi:10.1016/j.jacc.2012.02.008

Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice.

EuroThrombosis: annual meeting of the European Society of Cardiology Working Group on Thrombosis

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Authors: Giulio Coluzzi, Eliano Pio Navarese and Felicita Andreotti
Journal: Expert review of hematology
Issue: Expert Rev. Hematol. 5(1), 39–42 (2012)

EuroThrombosis Summit

Oporto, Portugal, 7–8 October 2011

EuroThrombosis is the annual meeting of the European Society of Cardiology Working Group on Thrombosis. It gathers clinicians and scientists interested in clinical/experimental thrombosis.
The 2011 congress was held in Oporto, Portugal, and presented an appealing program with state-of-the-art sessions on new antiplatelet/anticoagulant agents, diabetes, cellular mechanisms of thrombosis and miRNAs.

Bleeding risk assessment and management in atrial fibrillation patients

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Executive Summary of a Position Document from the European Heart Rhythm Association (EHRA), endorsed by the European Society of Cardiology (ESC) Working Group on Thrombosis

Authors: G. Y. H. Lip, F. Andreotti, L. Fauchier, K. Huber, E. Hylek, E. Knight, D. Lane, M. Levi, F. Marín, G. Palareti, P. Kirchhof

Journal: Thrombosis and Haemostasis

ISSN: 0340-6245


Issue: 2011: 106/6 (Dec) pp. 993-1234

Pages: 997-1011

Read the press release related to this position paper:  European experts issue position document on bleeding risk assessment and management in atrial fibrillation patients

In the December 2011 issue of Thrombosis and Haemostasis, an important position document from the European Heart Rhythm Association [EHRA] and the European Society of Cardiology [ESC] Working Group on Thrombosis on bleeding risk assessment and management in atrial fibrillation patients is published.

Bleeding in acute coronary syndromes and percutaneous coronary interventions

A position paper of the Working Group Thrombosis of the ESC

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Authors: Philippe Gabriel Steg (France), Kurt Huber (Austria), Felicita Andreotti (Italy), Harald Arnesen (Norway), Dan Atar (Norway), Lina Badimon (Spain), Jean-Pierre Bassand (France), Raffaele De Caterina (Italy), John A. Eikelboom (Canada), Dietrich Gulba (Germany), Martial Hamon (France), Ge´rard Helft (France), Keith A.A. Fox (UK), Steen D. Kristensen (Denmark), Sunil V. Rao (USA), Freek W. A. Verheugt (Netherlands), Petr Widimsky (Czech Republic), Uwe Zeymer (Germany), and Jean-Philippe Collet (France)

European Heart Journal- 2011; DOI: 10.1093/eurheartj/ehr204; First Published on line: 29 June  2011

Read the press release related to this position paper:  ESC calls for greater awareness of potential for adverse events from bleeding as a result of PCI

The position paper, published online today in The European Heart Journal, summarises current knowledge regarding the epidemiology of bleeding in ACS and PCI, and provides a European perspective on management strategies to minimise the extent of bleeding and subsequent adverse consequences. 

Operative management of antiplatelet therapy in patients with coronary artery disease

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Joint position paper by members of the working group on Perioperative Haemostasis of the Society on Thrombosis and Haemostasis Research (GTH), the working group on Perioperative Coagulation of the Austrian Society for Anesthesiology, Resuscitation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the ESC

Authors: W. Korte, M. Cattaneo, P.-G. Chassot, S. Eichinger, C. von Heymann, N. Hofmann, H. Rickli, M. Spannagl, B. Ziegler, F. Verheugt, K. Huber

Thrombosis and Haemostasis - 2011: 105/5(May) pp. 743-932; DOI: 10.1160/TH10-04-0217

Management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting With Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/ Stenting

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Gregory Y. H. Lip; Kurt Huber; Felicita Andreotti; Harald Arnesen; K. Juhani Airaksinen; Thomas Cuisset; Paulus Kirchhof; Francisco Marín

Document Reviewers: A. Rubboli, A. J. Camm, H. Heidbuchel, E. Hoffmann, N. Reifart, F. Ribichini, F. Verheugt

Interindividual variability in the response to oral antiplatelet drugs  

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A position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology

Authors: Wiktor Kuliczkowski, Adam Witkowski, Lech Polonski, Cezary Watala, Krzysztof Filipiak, Andrzej Budaj, Jacek Golanski, Dariusz Sitkiewicz,
Jerzy Pregowski, Jacek Gorski, Marian Zembala, Grzegorz Opolski, Kurt Huber,Harald Arnesen, Steen D. Kristensen, and Raffaele De Caterina

Pre-hospital reperfusion therapy: a strategy to improve therapeutic outcome in patients with ST-elevation myocardial infarction

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by Kurt Huber, Raffaele De Caterina, Steen D. Kristensen, Freek W.A. Verheugt, Gilles Montalescot, Lina Badimon Maestro, Frans Van de Werf for the Task Force on Pre-hospital Reperfusion Therapy of the Working Group on Thrombosis of the ESC

Eur. Heart J., October 2005; 26: 2063 - 2074.

Expert ConsensusDocument on the Use of Antiplatelet Agents

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The Task Force on the Use of Antiplatelet Agents in Patients with Atherosclerotic Cardiovascular Disease of the European Society of Cardiology: Carlo Patrono (Chairperson), Fedor Bachmann, Colin Baigent, Christopher Bode, Raffaele De Caterina, Bernard Charbonnier, Desmond Fitzgerald, Jack Hirsh, Steen Husted, Jan Kvasnicka, Gilles Montalescot, Luis Alberto Garcı´a Rodrı´guez, Freek Verheugt, Jozef Vermylen, Lars Wallentin

EHJ 2004;25:166-181