Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis.

Despite the clear net clinical benefit of oral anticoagulation (OAC) in atrial fibrillation (AF) patients at risk for stroke, major bleeding events (especially intra-cranial bleeds) may be devastating events when they do occur. The decision for OAC is often based on a careful assessment of both stroke risk and bleeding risk, but clinical scores for bleeding risk estimation are much less well validated than stroke risk scales. Also, the estimation of bleeding risk is rendered difficult since many of the known factors that increase bleeding risk overlap with stroke risk factors. As well as this, many factors that increase bleeding risk are transient, such as variable international normalized ratio values, operations, vascular procedures, or drug-drug and food-drug interactions. In this Position Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in AF patients, with a view to summarizing 'best practice' when approaching antithrombotic therapy in AF patients. We address the epidemiology and size of the problem of bleeding risk in AF and review established bleeding risk factors. We also summarize definitions of bleeding in the published literature. Patient values and preferences balancing the risk of bleeding against thrombo-embolism is reviewed, and the prognostic implications of bleeding are discussed. We also review bleeding risk stratification and currently published bleeding risk schema. A brief discussion of special situations [e.g. peri-ablation, peri-devices (implantable cardioverter-defibrillator, pacemakers) and presentation with acute coronary syndromes and/or requiring percutaneous coronary interventions/stents and bridging therapy], as well as a discussion of prevention of bleeds and managing bleeding complications, is made. Finally, this document also puts forwards consensus statements that may help to define evidence gaps and assist in everyday clinical practice. Bleeding risk is almost inevitably lower than stroke risk in patients with atrial fibrillation. Nonetheless, identification of patients at high risk of bleeding and delineation of conditions and situations associated with bleeding risk can help to refine antithrombotic therapy to minimize bleeding risk.

[1]  B. Gage,et al.  The Effect of Stroke and Stroke Prophylaxis With Aspirin or Warfarin on Quality of Life , 1996 .

[2]  G. Breithardt,et al.  An international survey of physician and patient understanding, perception, and attitudes to atrial fibrillation and its contribution to cardiovascular disease morbidity and mortality , 2010, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[3]  G. Lip,et al.  Patient knowledge and perceptions of atrial fibrillation and anticoagulant therapy: effects of an educational intervention programme. The West Birmingham Atrial Fibrillation Project. , 2006, International journal of cardiology.

[4]  K. Huber,et al.  Antiplatelet therapy and coronary stents in perioperative medicine--the two sides of the coin. , 2008, Best practice & research. Clinical anaesthesiology.

[5]  Margaret C Fang,et al.  Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation , 2004, Annals of Internal Medicine.

[6]  P. Mannucci,et al.  Drug therapy: Prevention and treatment of major blood loss , 2007 .

[7]  Elia Biganzoli,et al.  Updated Worldwide Survey on the Methods, Efficacy, and Safety of Catheter Ablation for Human Atrial Fibrillation , 2005, Circulation. Arrhythmia and electrophysiology.

[8]  P. Gregory,et al.  Upper gastrointestinal bleeding , 1981, Digestive Diseases and Sciences.

[9]  J. Vandenbroucke,et al.  Optimal oral anticoagulant therapy in patients with mechanical heart valves. , 1995, The New England journal of medicine.

[10]  E. Blackstone,et al.  Success of surgical left atrial appendage closure: assessment by transesophageal echocardiography. , 2008, Journal of the American College of Cardiology.

[11]  M. Gold Effect of Home Testing of International Normalized Ratio on Clinical Events , 2011 .

[12]  R. Abbate,et al.  Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years. , 2009, Journal of the American College of Cardiology.

[13]  S. Greenberg,et al.  Should anticoagulation be resumed after intracerebral hemorrhage? , 2010, Cleveland Clinic Journal of Medicine.

[14]  J. Brachmann,et al.  Atrial Fibrillation Ablation in Patients with Therapeutic International Normalized Ratios , 2009, Pacing and clinical electrophysiology : PACE.

[15]  P Michael Ho,et al.  Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. , 2008, JAMA.

[16]  J. Douketis,et al.  Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin k in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial☆ , 2003 .

[17]  H. O'kane The optimal intensity of vitamin K antagonists in patients with mechanical heart valves: a meta-analysis. , 2004, Journal of the American College of Cardiology.

[18]  L. Køber,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 , 2009, The Lancet.

[19]  G. Lip,et al.  Consensus document on antithrombotic therapy in the setting of electrophysiological procedures. , 2008, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[20]  S. Mayer,et al.  Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion. , 2007, Mayo Clinic proceedings.

[21]  J. Cook,et al.  Warfarin plus Aspirin after Myocardial Infarction or the Acute Coronary Syndrome: Meta-Analysis with Estimates of Risk and Benefit , 2005, Annals of Internal Medicine.

[22]  S. Knaub,et al.  Prothrombin complex concentrate (Beriplex® P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial , 2008, Journal of thrombosis and haemostasis : JTH.

[23]  D. Redelmeier,et al.  Prognostic Implications of Warfarin Cessation After Major Trauma: A Population-Based Cohort Analysis , 2005, Circulation.

[24]  R. Beyth,et al.  Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[25]  W. Lehmacher,et al.  Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin and Oral Anticoagulants for Prevention of Thromboembolic Complications in Cardioversion of Nonvalvular Atrial Fibrillation: The Anticoagulation in Cardioversion using Enoxaparin (ACE) Trial , 2004, Circulation.

[26]  J. Douketis,et al.  Oral Vitamin K Lowers the International Normalized Ratio More Rapidly Than Subcutaneous Vitamin K in the Treatment of Warfarin-Associated Coagulopathy , 2002, Annals of Internal Medicine.

[27]  Ottavio Alfieri,et al.  Corrigendum to: ‘Guidelines for the management of atrial fibrillation’ [European Heart Journal (2010) 31, 2369–2429 and EP-Europace (2010) 12, 1360–1420] , 2011 .

[28]  K. Hovingh,et al.  Bleeding complications in patients on anticoagulants who would have been disqualified for clinical trials , 2008, Thrombosis and Haemostasis.

[29]  A. Mehdipour,et al.  The impact of genetic polymorphisms and patient characteristics on warfarin dose requirements: a cross-sectional study in Iran. , 2010, Clinical therapeutics.

[30]  Andreas Metzner,et al.  Long-Term Results of Catheter Ablation in Paroxysmal Atrial Fibrillation: Lessons From a 5-Year Follow-Up , 2010, Circulation.

[31]  Martha J. Radford,et al.  Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation , 2001 .

[32]  J. Dimarco,et al.  Factors Affecting Bleeding Risk During Anticoagulant Therapy in Patients With Atrial Fibrillation: Observations From the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study , 2005 .

[33]  J. Broderick,et al.  The increasing incidence of anticoagulant-associated intracerebral hemorrhage , 2007, Neurology.

[34]  M. Rich,et al.  Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). , 2006, American heart journal.

[35]  M. Monreal,et al.  Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry , 2008, Thrombosis and Haemostasis.

[36]  L. Mantovani,et al.  A national survey of the management of atrial fibrillation with antithrombotic drugs in Italian primary care , 2010, Thrombosis and Haemostasis.

[37]  Gregory W Albers,et al.  Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. , 2007, Archives of internal medicine.

[38]  David O. Martin,et al.  Radiofrequency ablation of atrial fibrillation under therapeutic international normalized ratio: a safe and efficacious periprocedural anticoagulation strategy. , 2009, Heart rhythm.

[39]  J. Dahlerup,et al.  Major haemorrhagic complications during oral anticoagulant therapy in a Danish Population‐based cohort , 1997, Journal of internal medicine.

[40]  G. Lip Anticoagulation therapy and the risk of stroke in patients with atrial fibrillation at ‘moderate risk’ [CHADS2 score=1]: Simplifying stroke risk assessment and thromboprophylaxis in real-life clinical practice , 2010, Thrombosis and Haemostasis.

[41]  M. Sudlow,et al.  A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences. , 1998, The British journal of general practice : the journal of the Royal College of General Practitioners.

[42]  D. Kereiakes,et al.  Randomized Double-Blind Assessment of the ONSET and OFFSET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease: The ONSET/OFFSET Study , 2009, Circulation.

[43]  Gregory Y H Lip,et al.  A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. , 2010, Chest.

[44]  J. Daubert,et al.  Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. , 2007, European heart journal.

[45]  G. Lip,et al.  Treatments for stroke prevention in atrial fibrillation: A network meta-analysis and indirect comparisons versus dabigatran etexilate , 2010, Thrombosis and Haemostasis.

[46]  Carl R May,et al.  A patient decision aid to support shared decision-making on anti-thrombotic treatment of patients with atrial fibrillation: randomised controlled trial , 2007, Quality and Safety in Health Care.

[47]  M. Gold Preparation for pacemaker or implantable cardiac defibrillator implants in patients with high risk of thrombo-embolic events: oral anticoagulation or bridging with intravenous heparin? A prospective randomized trial , 2010 .

[48]  N. Weissman,et al.  Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. , 2003, The American journal of cardiology.

[49]  B. Strauss,et al.  Predictors and 1-year outcome of major bleeding in patients with non-ST-elevation acute coronary syndromes: insights from the Canadian Acute Coronary Syndrome Registries. , 2005, American heart journal.

[50]  G. Baumann,et al.  Is Antiarrhythmia Device Implantation Safe Under Dual Antiplatelet Therapy? , 2010, Pacing and clinical electrophysiology : PACE.

[51]  S. Steinhubl,et al.  Variation in the definitions of bleeding in clinical trials of patients with acute coronary syndromes and undergoing percutaneous coronary interventions and its impact on the apparent safety of antithrombotic drugs. , 2007, American heart journal.

[52]  J. Vandenbroucke,et al.  Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. , 1993, Archives of internal medicine.

[53]  Andrea Natale,et al.  Percutaneous Closure of the Left Atrial Appendage. , 2012, Cardiac electrophysiology clinics.

[54]  Claudia Stöllberger,et al.  Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. , 2004, European heart journal.

[55]  R Roberts,et al.  Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. , 1987, Circulation.

[56]  D. Schroeder,et al.  Time and Cardiac Risk of Surgery after Bare-metal Stent Percutaneous Coronary Intervention , 2008, Anesthesiology.

[57]  O. Benavente,et al.  Increased Risk of Intracranial Hemorrhage when Aspirin Is Combined with Warfarin: A Meta-Analysis and Hypothesis , 1999, Cerebrovascular Diseases.

[58]  Bernhard Meier,et al.  Percutaneous left atrial appendage transcatheter occlusion (PLAATO system) to prevent stroke in high-risk patients with non-rheumatic atrial fibrillation: results from the international multi-center feasibility trials. , 2005, Journal of the American College of Cardiology.

[59]  C. Legnani,et al.  Oral Anticoagulant Therapy in Patients with Nonrheumatic Atrial Fibrillation and Risk of Bleeding , 2001, Thrombosis and Haemostasis.

[60]  L Goldman,et al.  Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. , 1989, The American journal of medicine.

[61]  J. Douketis,et al.  The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[62]  T Fahey,et al.  The impact of patients' preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis. , 2000, BMJ : British Medical Journal.

[63]  P. Lavori,et al.  Effect of home testing of international normalized ratio on clinical events. , 2010, The New England journal of medicine.

[64]  W Klein,et al.  Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). , 2004, European heart journal.

[65]  S. Yusuf,et al.  Adverse Impact of Bleeding on Prognosis in Patients With Acute Coronary Syndromes , 2006, Circulation.

[66]  Donald Martin,et al.  Risk Factors for Complications of Chronic Anticoagulation: A Multicenter Study , 1993, Annals of Internal Medicine.

[67]  Stroke Investigators Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study , 1994, The Lancet.

[68]  P. Serruys,et al.  Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions , 2007, Circulation.

[69]  S. Borzak,et al.  How safely and for how long can warfarin therapy be withheld in prosthetic heart valve patients hospitalized with a major hemorrhage? , 2001, Chest.

[70]  Arcadio García-Alberola,et al.  Registro Español de Ablación con Catéter.V Informe Oficial de la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología (2005) , 2006 .

[71]  Carlo Boffano,et al.  Radiofrequency Catheter Ablation of Atrial Fibrillation: A Cause of Silent Thromboembolism?: Magnetic Resonance Imaging Assessment of Cerebral Thromboembolism in Patients Undergoing Ablation of Atrial Fibrillation , 2010, Circulation.

[72]  Susan Regan,et al.  Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation , 2007, Circulation.

[73]  J. Ornato,et al.  ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation , 2007, Circulation.

[74]  S. Olsson,et al.  Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial , 2003, The Lancet.

[75]  A. García-Alberola,et al.  [Spanish Catheter Ablation Registry. Fifth official report of the Spanish Society of Cardiology Working Group on Electrophysiology and Arrhythmias (2005)]. , 2006, Revista espanola de cardiologia.

[76]  J. Healey,et al.  Postoperative Low‐Molecular‐Weight Heparin Bridging Is Associated with an Increase in Wound Hematoma Following Surgery for Pacemakers and Implantable Defibrillators , 2009, Pacing and clinical electrophysiology : PACE.

[77]  Salim Yusuf,et al.  Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. , 2009, American heart journal.

[78]  J. Hirsh,et al.  Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[79]  S. Schulman,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients , 2005, Journal of thrombosis and haemostasis : JTH.

[80]  Bernhard Meier,et al.  Left atrial appendage closure with Amplatzer cardiac plug in atrial fibrillation: initial European experience. , 2011, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[81]  E. Antman,et al.  ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use , 2008, The American Journal of Gastroenterology.

[82]  D Bergqvist,et al.  Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients , 2010, Journal of thrombosis and haemostasis : JTH.

[83]  Dwight E. Peake,et al.  Thrombolysis in myocardial infarction (TIMI) trial: Phase I. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase , 1988 .

[84]  G. Lip,et al.  Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. , 2007, QJM : monthly journal of the Association of Physicians.

[85]  G. Lip Chronic renal disease and stroke in atrial fibrillation: balancing the prevention of thromboembolism and bleeding risk. , 2011, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[86]  P. Mannucci,et al.  Prevention and treatment of major blood loss. , 2007, The New England journal of medicine.

[87]  D. Singer,et al.  Warfarin Discontinuation After Starting Warfarin for Atrial Fibrillation , 2010, Circulation. Cardiovascular quality and outcomes.

[88]  J. Ware,et al.  Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial , 2007, The Lancet.

[89]  J. Hallas,et al.  Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study , 2006, BMJ : British Medical Journal.

[90]  P. R. R. Ecurrent,et al.  EFFECTS OF CLOPIDOGREL IN ADDITION TO ASPIRIN IN PATIENTS WITH ACUTE CORONARY SYNDROMES WITHOUT ST-SEGMENT ELEVATION , 2001 .

[91]  L. Díaz-Flores,et al.  [Disseminated intravascular coagulation]. , 1977, Actas dermo-sifiliograficas.

[92]  P. Reitsma,et al.  A C1173T Dimorphism in the VKORC1 Gene Determines Coumarin Sensitivity and Bleeding Risk , 2005, PLoS medicine.

[93]  H. Calkins,et al.  Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group. , 1999, Circulation.

[94]  A. Laupacis,et al.  Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. , 2005, Archives of internal medicine.

[95]  W. Ageno,et al.  Treatment of coumarin‐associated coagulopathy: a systematic review and proposed treatment algorithms , 2006, Journal of thrombosis and haemostasis : JTH.

[96]  Richard Sutton,et al.  Guidelines for cardiac pacing and cardiac resynchronization therapy. The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. , 2007, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[97]  R. Hunter,et al.  Uninterrupted Warfarin for Periprocedural Anticoagulation in Catheter Ablation of Typical Atrial Flutter: A Safe and Cost‐Effective Strategy , 2010, Journal of cardiovascular electrophysiology.

[98]  Yuchiao Chang,et al.  Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? , 2003, JAMA.

[99]  A. Kastrati,et al.  Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation , 2008, Journal of internal medicine.

[100]  P. Kamphuisen,et al.  Management strategies for optimal control of anticoagulation in patients with atrial fibrillation. , 2009, Seminars in thrombosis and hemostasis.

[101]  A Laupacis,et al.  A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial. , 1999, JAMA.

[102]  Sharon E Straus,et al.  Impact of a patient decision aid on care among patients with nonvalvular atrial fibrillation: a cluster randomized trial , 2005, Canadian Medical Association Journal.

[103]  A. Colombo,et al.  Incidence and Predictors of Drug-Eluting Stent Thrombosis During and After Discontinuation of Thienopyridine Treatment , 2007, Circulation.

[104]  H. Halkin,et al.  Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. , 2003, Archives of internal medicine.

[105]  A. Kastrati,et al.  Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. , 2008, Journal of the American College of Cardiology.

[106]  B. Gage,et al.  Cost-effectiveness of preference-based antithrombotic therapy for patients with nonvalvular atrial fibrillation. , 1998, Stroke.

[107]  Gregory Y H Lip,et al.  Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. , 2011, Journal of the American College of Cardiology.

[108]  G. Montalescot,et al.  Optimizing long-term dual aspirin/clopidogrel therapy in acute coronary syndromes: when does the risk outweigh the benefit? , 2009, International journal of cardiology.

[109]  H. Thai,et al.  The Relationship between Warfarin, Aspirin, and Clopidogrel Continuation in the Peri‐procedural Period and the Incidence of Hematoma Formation after Device Implantation , 2010, Pacing and clinical electrophysiology : PACE.

[110]  D K Owens,et al.  Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. , 1995, JAMA.

[111]  J. Douketis,et al.  Perioperative anticoagulation in patients having implantation of a cardiac pacemaker or defibrillator: a systematic review and practical management guide , 2008, Journal of thrombosis and haemostasis : JTH.

[112]  Jonathan D Mahnken,et al.  Development of a contemporary bleeding risk model for elderly warfarin recipients. , 2006, Chest.

[113]  J. Ornato,et al.  ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiov , 2007, Circulation.

[114]  G. Guyatt,et al.  Values and preferences in oral anticoagulation in patients with atrial fibrillation, physicians' and patients' perspectives: protocol for a two-phase study , 2008, BMC health services research.

[115]  B. Cosmi,et al.  Bleeding with anticoagulation therapy – Who is at risk, and how best to identify such patients , 2009, Thrombosis and Haemostasis.

[116]  Jeroen J. Bax,et al.  Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). , 2010, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[117]  E. Hylek,et al.  Warfarin for atrial fibrillation in community‐based practise , 2008, Journal of thrombosis and haemostasis : JTH.

[118]  M. Prins,et al.  Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. , 1999, Archives of internal medicine.

[119]  S. Yusuf,et al.  Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial Fibrillation Depends on the Quality of International Normalized Ratio Control Achieved by Centers and Countries as Measured by Time in Therapeutic Range , 2008, Circulation.

[120]  Mark Crowther,et al.  Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[121]  R. Meuli,et al.  The Acute STroke Registry and Analysis of Lausanne (ASTRAL): Design and Baseline Analysis of an Ischemic Stroke Registry Including Acute Multimodal Imaging , 2010, Stroke.

[122]  R. Califf,et al.  Incidence and Predictors of Bleeding After Contemporary Thrombolytic Therapy for Myocardial Infarction , 1997 .

[123]  S. Yusuf,et al.  Dabigatran and Warfarin in Vitamin K Antagonist–Naive and –Experienced Cohorts With Atrial Fibrillation , 2010, Circulation.

[124]  M. Levi,et al.  Invasive procedures in the outpatient setting: Managing the short-acting acenocoumarol and the long-acting phenprocoumon , 2007, Thrombosis and Haemostasis.

[125]  R Fuller,et al.  Risk communication and older people-understanding of probability and risk information by medical inpatients aged 75 years and older. , 2001, Age and ageing.

[126]  C. Good,et al.  Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care. , 2005, Journal of general internal medicine.

[127]  D. Singer,et al.  The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. , 2004, Archives of internal medicine.

[128]  S. Connolly,et al.  Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. , 2011, The Canadian journal of cardiology.

[129]  H. Ehrlich,et al.  Safety of factor VIII inhibitor bypass activity (FEIBA®): 10‐year compilation of thrombotic adverse events , 2002, Haemophilia : the official journal of the World Federation of Hemophilia.

[130]  Claes Held,et al.  Ticagrelor versus clopidogrel in patients with acute coronary syndromes. , 2009, The New England journal of medicine.

[131]  M. Fredrikson,et al.  To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial. , 2010, British journal of anaesthesia.

[132]  Sunil V. Rao,et al.  Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. , 2004, JAMA.

[133]  G. Biondi-Zoccai,et al.  Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures; Systematic overview and meta-analysis of randomized trials. , 2004, Journal of the American College of Cardiology.

[134]  A. Laupacis,et al.  Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. , 1999, Archives of internal medicine.

[135]  T. Olsen,et al.  Hemorrhagic and Ischemic Strokes Compared: Stroke Severity, Mortality, and Risk Factors , 2009, Stroke.

[136]  H. Schunkert,et al.  Pocket hematoma after pacemaker or implantable cardioverter defibrillator surgery: influence of patient morbidity, operation strategy, and perioperative antiplatelet/anticoagulation therapy. , 2004, Chest.

[137]  S. Barold,et al.  Pacemaker and Implantable Cardioverter Defibrillator Implantation Without Reversal of Warfarin Therapy , 2004, Pacing and clinical electrophysiology : PACE.

[138]  E. J. PubMed Citation,et al.  An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction , 2009 .

[139]  E. Aliot,et al.  Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. , 2006, European heart journal.

[140]  D. Armstrong,et al.  Implementing evidence based medicine in general practice: audit and qualitative study of antithrombotic treatment for atrial fibrillation , 1999, BMJ.

[141]  Joanna E Cohen,et al.  Universities and tobacco money , 2001, BMJ : British Medical Journal.

[142]  G. Lip,et al.  Oral anticoagulation in atrial fibrillation: A pan-European patient survey. , 2007, European journal of internal medicine.

[143]  V. Budhraja The net clinical benefit of warfarin anticoagulation in atrial fibrillation. , 2010, Annals of internal medicine.

[144]  Deepak L. Bhatt,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. , 2008, Circulation.

[145]  W. Ahmad Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. , 2009 .

[146]  Helmut Baumgartner,et al.  Guidelines on the management of valvular heart disease The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology , 2007 .

[147]  K. Lee,et al.  Incidence and predictors of bleeding after contemporary thrombolytic therapy for myocardial infarction. The Global Utilization of Streptokinase and Tissue Plasminogen activator for Occluded coronary arteries (GUSTO) I Investigators. , 1997, Circulation.

[148]  H. Katayama,et al.  Contrast sonography for detection of vesicoureteral reflux , 1994, The Lancet.

[149]  Palle Petersen,et al.  Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. , 2005, JAMA.

[150]  R. Beyth,et al.  Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. , 1998, The American journal of medicine.

[151]  Harold T. Dodge,et al.  Thrombolysis inMyocardial Infarction (TIMI) Trial, Phase I:acomparison between intravenous tissue plasminogen activator andintravenous streptokinase* , 1987 .

[152]  N. Dudley,et al.  Avoidance hierarchies and preferences for anticoagulation--semi-qualitative analysis of older patients' views about stroke prevention and the use of warfarin. , 2004, Age and ageing.

[153]  angesichts der Corona-Pandemie,et al.  UPDATE , 1973, The Lancet.

[154]  P. Wells,et al.  The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism. , 2003, Archives of internal medicine.

[155]  R. Thomson,et al.  Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation , 2000, The Lancet.

[156]  D. Singer,et al.  Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators , 2009, Stroke.

[157]  Oral Vitamin K Versus Placebo to Correct Excessive Anticoagulation in Patients Receiving Warfarin , 2009 .

[158]  Timothy J Gardner,et al.  Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American D , 2007, Circulation.

[159]  Gregory Y H Lip,et al.  Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. , 2010, Chest.

[160]  E. Hylek,et al.  New-onset atrial fibrillation and warfarin initiation: High risk periods and implications for new antithrombotic drugs , 2010, Thrombosis and Haemostasis.

[161]  David L Veenstra,et al.  Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. , 2002, JAMA.

[162]  A. Gavazzi,et al.  Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. , 2008, The American journal of cardiology.

[163]  A. Laupacis,et al.  Warfarin for atrial fibrillation. The patient's perspective. , 1996, Archives of internal medicine.

[164]  J. Cox,et al.  Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. , 2001, BMJ : British Medical Journal.

[165]  Arcadio García-Alberola,et al.  [Spanish Registry of Catheter Ablation. Third Official Report of the Working Group on Electrophysiology and Arrhythmias of the Spanish Society of Cardiology (2003)]. , 2004, Revista espanola de cardiologia.

[166]  M. Prins,et al.  Safety of Treatment with Oral Anticoagulants in the Elderly , 1999, Drugs & aging.

[167]  Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? , 2003 .

[168]  J. Ornato,et al.  [ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery]. , 2009, Masui. The Japanese journal of anesthesiology.

[169]  A. Gallus,et al.  Trial of different intensities of anticoagulation in patients with prosthetic heart valves. , 1990, The New England journal of medicine.

[170]  R B D'Agostino,et al.  Stroke severity in atrial fibrillation. The Framingham Study. , 1996, Stroke.

[171]  S. Yusuf,et al.  Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. , 2006, JAMA.

[172]  F. Lombardi,et al.  Antithrombotic treatment in real-life atrial fibrillation patients: A report from the Euro Heart Survey on Atrial Fibrillation , 2006 .

[173]  C. Lien Cardiac Risk of Noncardiac Surgery after Percutaneous Coronary Intervention with Drug-eluting Stents , 2009 .

[174]  Ross Upshur,et al.  Patients' perspectives on taking warfarin: qualitative study in family practice , 2004, BMC family practice.

[175]  A. Laupacis,et al.  The effect of qualitative vs. quantitative presentation of probability estimates on patient decision‐making: a randomized trial , 2002, Health expectations : an international journal of public participation in health care and health policy.

[176]  H. White,et al.  Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation : stroke prevention in atrial fibrillation II study. Commentary , 1994 .

[177]  Assent investigators Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction , 2001, The Lancet.

[178]  M. Valgimigli,et al.  Rationale and use of antiplatelet and antithrombotic drugs during cardiovascular interventions: May 2010 update. , 2008, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[179]  Antonio Colombo,et al.  Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. , 2005, European heart journal.

[180]  J. Dimarco,et al.  Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. , 2005, American heart journal.

[181]  M. Pfeffer,et al.  Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial , 2006, The Lancet.

[182]  A. Holbrook,et al.  Influence of decision aids on patient preferences for anticoagulant therapy: a randomized trial , 2007, Canadian Medical Association Journal.

[183]  H. Büller,et al.  Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based. , 2008, Blood.

[184]  Bertil Olsson,et al.  Outcome parameters for trials in atrial fibrillation: executive summary. , 2007, European heart journal.

[185]  S. de Servi,et al.  Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of 'bridging' antiplatelet therapy with tirofiban during temporary withdrawal of clopidogrel. , 2010, British journal of anaesthesia.

[186]  F. Morady,et al.  A randomized trial comparing heparin initiation 6 h or 24 h after pacemaker or defibrillator implantation. , 2000, Journal of the American College of Cardiology.

[187]  P. Kirchhof,et al.  Management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/ Stenting , 2009, Thrombosis and Haemostasis.

[188]  Salim Yusuf,et al.  Effect of clopidogrel added to aspirin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[189]  Vittorio Pengo,et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT) , 1996, The Lancet.

[190]  M. Keltai,et al.  Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial , 2008, The Lancet.

[191]  J. Conard,et al.  La prise en charge périopératoire des traitements antithrombotiques. Des recommandations de l’American College of Chest Physicians (ACCP) à celles de la Haute Autorité de santé (HAS) , 2010 .

[192]  Gregory Y H Lip,et al.  Quality of life in patients with atrial fibrillation: a systematic review. , 2006, The American journal of medicine.

[193]  Dhanunjaya R. Lakkireddy,et al.  Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation: The Impact of Periprocedural Therapeutic International Normalized Ratio , 2010, Circulation.

[194]  A. Forster,et al.  Effect of study setting on anticoagulation control: a systematic review and metaregression. , 2006, Chest.

[195]  K. Peter,et al.  New oral anticoagulant drugs in cardiovascular disease , 2010, Thrombosis and Haemostasis.

[196]  E. Hylek,et al.  Risk Factors for Intracranial Hemorrhage in Outpatients Taking Warfarin , 1994, Annals of Internal Medicine.

[197]  J. Olsen,et al.  Upper gastrointestinal bleeding among users of NSAIDs: a population-based cohort study in Denmark. , 2002, British journal of clinical pharmacology.

[198]  S. Yusuf,et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. , 2001, The New England journal of medicine.

[199]  S. Yusuf,et al.  Dabigatran versus warfarin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[200]  Maurice Buchbinder,et al.  Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial , 2009, The Lancet.

[201]  P. Strengers,et al.  Individualized dosing regimen for prothrombin complex concentrate more effective than standard treatment in the reversal of oral anticoagulant therapy: an open, prospective randomized controlled trial. , 2006, Thrombosis research.

[202]  Robby Nieuwlaat,et al.  Revised A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey , 2012 .