Thromb Haemost 2011; 106(06): 997-1011.
DOI: 10.1160/TH11-10-0690
Position Paper
Schattauer GmbH

Bleeding risk assessment and management in atrial fibrillation patients

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
Gregory Y. H. Lip*
1   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
,
Felicita Andreotti**
2   Department of Cardiovascular Medicine, “A. Gemelli” University Hospital, Rome, Italy
,
Laurent Fauchier
3   Cardiologie B, Centre Hospitalier Universitaire Trousseau et Université François Rabelais, Tours, France
,
Kurt Huber**
4   3rd Dept of Medicine, Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria
,
Elaine Hylek
5   Department of Medicine, Research Unit-Section of General Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
,
Eve Knight
6   Patient Representative, AntiCoagulation Europe, Bromley, UK
,
Deirdre Lane
1   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
,
Marcel Levi
7   Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
,
Francisco Marin
8   Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
,
Gualtiero Palareti
9   Department of Angiology and Blood Coagulation, University Hospital S. Orsola-Malpighi, Bologna, Italy
,
Paulus Kirchhof***
5   Department of Medicine, Research Unit-Section of General Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
5   Department of Medicine, Research Unit-Section of General Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
,
J.-P. Collet
,
A. Rubboli
,
D. Poli
,
A. J. Camm
› Author Affiliations
Further Information

Publication History

Received: 05 October 2011

Accepted after minor revision: 27 October 2011

Publication Date:
15 December 2017 (online)

Summary

In this executive summary of a Consensus Document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in atrial fibrillation (AF) patients. The main aim of the document was to summarise ‘best practice’ in dealing with bleeding risk in AF patients when approaching antithrombotic therapy, by addressing the epidemiology and size of the problem, and review established bleeding risk factors. We also summarise definitions of bleeding in the published literature. Patient values and preferences balancing the risk of bleeding against thromboembolism as well as the prognostic implications of bleeding are reviewed. We also provide an overview of published bleeding risk stratification and bleeding risk schema. Brief discussion of special situations (e.g. periablation, peri-devices such as implantable cardioverter defibrillators [ICD] or pacemakers, presentation with acute coronary syndromes and/or requiring percutanous coronary interventions/stents and bridging therapy) is made, as well as a discussion of the prevention of bleeds and managing bleeding complications. Finally, this document puts forwards consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

* Chair of the Task Force


** Representing the ESC Working Group on Thrombosis


*** Co-Chair of the Task Force


# The full version of this document has been published in Europace 2011; 13: 723–460.


 
  • References

  • 1 Kirchhof P. et al. Outcome parameters for trials in atrial fibrillation: executive summary: Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eur Heart J 2007; 28: 2803-2817.
  • 2 Camm AJ. 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). Europace 2010; 12: 1360-1420.
  • 3 Singer DE. et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151: 297-305.
  • 4 Ahrens I. et al. New oral anticoagulant drugs in cardiovascular disease. Thromb Haemost 2010; 104: 49-60.
  • 5 Roskell NS. et al. Treatments for stroke prevention in atrial fibrillation: a network meta-analysis and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2010; 104: 1106-1115.
  • 6 Ogilvie IM. et al. Ischaemic stroke and bleeding rates in 'real-world' atrial fibrillation patients. Thromb Haemost 2011; 106: 34-44.
  • 7 Gage BF. et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
  • 8 Lip GY. 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. Chest 2010; 137: 263-272.
  • 9 Lip GY. Anticoagulation therapy and the risk of stroke in patients with atrial fibrillation al `moderate risk´ [CHADS2 score=1]: simplifying stroke risk assessment and thromboprophylaxis in real-life clinical practice. Thromb Haemost 2010; 103: 683-685.
  • 10 Lip GY. et al. 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. Europace 2011; 13: 723-746.
  • 11 Flaherty ML. et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68: 116-121.
  • 12 Nieuwlaat R. et al. on behalf of the Euro Heart Survey Investigators. Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. Eur Heart J 2006; 27: 3018-3026.
  • 13 Mazzaglia G. et al. A national survey of the management of atrial fibrillation with antithrombotic drugs in Italian primary care. Thromb Haemost 2010; 103: 968-975.
  • 14 Garcia DA. et al. New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb Haemost 2010; 104: 1099-1105.
  • 15 Ezekowitz MD. et al. the RE-LY Steering Committee and Investigators. Dabigatran and Warfarin in Vitamin K Antagonist-Naive and -Experienced Cohorts With Atrial Fibrillation. Circulation 2010; 122: 2246-2253.
  • 16 Atrial Fibrillation Investigators Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154: 1449-1457.
  • 17 SPAF Investigators Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994; 343: 687-691.
  • 18 DiMarco JP. et al. Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: Observations from the AFFIRM Study. Am Heart J 2005; 149: 650-656.
  • 19 Executive Steering Committee for the SPORTIF III Investigators Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation. Lancet 2003; 362: 1691-1698.
  • 20 Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. J Am Med Assoc 2005; 293: 690-698.
  • 21 Active Writing Group on behalf of the Active Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events. Lancet 2006; 367: 1903-1912.
  • 22 Connolly SJ. et al. (RE-LY Steering Committee and Investigators) Dabigatran vs. Warfarin in patients with Atrial Fibrillation. N Engl J Med 2009; 361: 1139-1151.
  • 23 Patel MR. et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
  • 24 Granger CB. et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992.
  • 25 Landefeld CS, Goldman OL. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med 1989; 87: 144-152.
  • 26 Steffensen F. et al. Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort. J Intern Med 1997; 242: 497-503.
  • 27 Beyth RJ. et al. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
  • 28 Hylek EM. et al. Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients with Atrial Fibrillation. Circulation 2007; 115: 2689-2696.
  • 29 Pengo V. et al. ISCOAT Study Group.(Italian Study on Complications of Oral Anticoagulant Therapy). Oral Anticoagulant Therapy in Patients with Nonrheumatic Atrial Fibrillation and Risk of Bleed. A Multicenter Inception Cohort Study. Thromb Haemost 2001; 85: 418-422.
  • 30 van der Meer FJ. et al. Bleeding complications in oral anticoagulant therapy: an analysis of risk factors. Arch Intern Med 1993; 153: 1557-1562.
  • 31 Fihn SD. et al. Risk factors for complications of chronic anticoagulation: a multicenter study. Ann Intern Med 1993; 118: 511-520.
  • 32 Go AS. et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: How well do randomized trials translate into clinical practice?. J Am Med Assoc 2003; 290: 2685-2691.
  • 33 Poli D. et al. Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years. J Am Coll Cardiol 2009; 54: 999-1002.
  • 34 Rose A. et al. Warfarin for Atrial Fibrillation in Community-Based Practice. J Thromb Haemost 2008; 6: 1647-1654.
  • 35 Poli D. et al. Italian Federation of Anticoagulation Clinics. Bleeding risk in very old patients on vitamin K antagonist treatment: results of a prospective collaborative study on elderly patients followed by Italian Centres for Anticoagulation. Circulation 2011; 124: 824-829.
  • 36 Hutten BA. et al. Safety of treatment with oral anticoagulants in the elderly. A systematic review. Drugs Aging 1999; 14: 303-312.
  • 37 Fang MC. et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004; 141: 745-752.
  • 38 Steger C. et al. Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. Eur Heart J 2004; 25: 1734-1740.
  • 39 Olesen JB. et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a 'real world' nationwide cohort study. Thromb Haemost 2011; 106: 739-751.
  • 40 Steinhubl SR. 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. Am Heart J 2007; 154: 3-11.
  • 41 Chesebro JH. 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. Circulation 1987; 76: 142-154.
  • 42 The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO Investigators. N Engl J Med 1993; 329: 673-682.
  • 43 Mehran R. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123: 2736-2747.
  • 44 Palareti G, Cosmi B. Bleeding with anticoagulation therapy - Who is at risk, and how best to identify such patients. Thromb Haemost 2009; 102: 268-278.
  • 45 Hughes M, Lip GY. Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. Quart J Med 2007; 100: 599-607.
  • 46 Schulman S. et al. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8: 202-204.
  • 47 Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001; 358: 605-613.
  • 48 Yusuf S. et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. 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.
  • 49 Stone GW. et al. Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial investigators. Bivalirudin in patiens with acute coronary syndromes undergoing percutaneous coronary intervention: a subgropu analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet 2007; 369: 907-919.
  • 50 Yusuf S. et al. Oasis-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. J Am Med Assoc 2006; 295: 1519-1530.
  • 51 Wallentin L. et al. : for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
  • 52 Palareti G. et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 1996; 348: 423-428.
  • 53 Kuijer PMM. et al. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159: 457-460.
  • 54 Wells PS. et al. The outpatient bleeding risk index: Validation of a tool for predicting bleeding rates in patients treated for deep vein thrombosis and pulmonary embolism. Arch Intern Med 2003; 163: 917-920.
  • 55 Aspinall SL. et al. Bleeding risk index in an anticoagulation clinic. Assessment by indication and implications for care. J Gen Intern Med 2005; 20: 1008-1013.
  • 56 Gage BF. et al. Clinical classification schemes for predicting haemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-719.
  • 57 Shireman I T. et al. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest 2006; 130: 1390-1396.
  • 58 Ruíz-Giménez N. et al. RIETE Investigators. Predictive variables for major bleeding events inpatients presenting with documented acute venous thromboembolism. Findings fromthe RIETE Registry. Thromb Haemost 2008; 100: 26-31.
  • 59 Goldstein JN, Greenberg SM. Should anticoagulation be resumed after intracerebral hemorrhage?. Cleve Clin J Med 2010; 77: 791-799.
  • 60 Saour JN. et al. Trial of different intensities of anticoagulation in patients with prosthetic heart valves. N Engl J Med 1990; 322: 428-432.
  • 61 Vink R. et al. The optimal intensity of vitamin K antagonists in patients with mechanical heart valves: a meta-analysis. J Am Coll Cardiol 2003; 42: 2042-2048.
  • 62 Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897-902.
  • 63 Cannegieter SC. et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11-17.
  • 64 White HD. et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167: 239-245.
  • 65 Connolly SJ. 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. Circulation 2008; 118: 2029-2037.
  • 66 van Walraven C. et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129: 1155-1166.
  • 67 Matchar DB. et al. THINRS Executive Committee and Site Investigators. Effect of home testing of international normalized ratio on clinical events. N Engl J Med 2010; 363: 1608-1620.
  • 68 Levi M. et al. Management strategies for optimal control of anticoagulation in patients with atrial fibrillation. Semin Thromb Hemost 2009; 35: 560-567.
  • 69 Higashi MK. et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. J Am Med Assoc 2002; 287: 1690-1698.
  • 70 Reitsma PH. et al. A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk. PLoS Med 2005; 2: e312
  • 71 Namazi S. et al. The impact of genetic polymorphisms and patient characteristics on warfarin dose requirements: a cross-sectional study in Iran. Clin Ther 2010; 32: 1050-1060.
  • 72 Ho LY. et al. Safety and efficacy of oral anticoagulation therapy in Chinese patients with concomitant atrial fibrillation and hypertension. J Hum Hypertens 2011; 25: 304-310.
  • 73 Levi M. et al. Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based. Blood 2008; 111: 4471-4476.
  • 74 Hart RG. et al. Increased risk of intracranial hemorrhage when aspirin is combined with warfarin: A meta-analysis and hypothesis. Cerebrovasc Dis 1999; 9: 215-217.
  • 75 Rothberg MB. et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005; 143: 241-250.
  • 76 Hallas J. et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. Br Med J 2006; 333: 726
  • 77 Sørensen R. 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. Lancet 2009; 374: 1967-1974.
  • 78 Mellemkjaer L. et al. Upper gastrointestinal bleeding among users of NSAIDs: a population-based cohort study in Denmark. Br J Clin Pharmacol 2002; 53: 173-181.
  • 79 Battistella M. et al. Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Arch Intern Med 2005; 165: 189-192.
  • 80 Man-Son-Hing M. et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159: 677-685.
  • 81 Levi M, Hovingh K. Bleeding complications in patients on anticoagulants who would have been disqualified for clinical trials. Thromb Haemost 2008; 100: 1047-1051.
  • 82 Pisters R. et al. A novel user-friendly score (HAS-BLED) to assess one year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest 2010; 138: 1093-1100.
  • 83 Fang MC. et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58: 395-401.
  • 84 Lip GY. 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. J Am Coll Cardiol 2011; 57: 173-180.
  • 85 Olesen JB. et al. Bleeding risk in 'real world' patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort. J Thromb Haemost 2011; 9: 1460-1467.
  • 86 Cairns JA. et al. CCS Atrial Fibrillation Guidelines Committee. Canadian cardiovascular society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol 2011; 27: 74-90.
  • 87 Lane DA. et al. Patient knowledge and perceptions of atrial fibrillation and anticoagulant therapy: effects of an educational intervention programme. The West Birmingham Atrial Fibrillation Project. Int J Cardiol 2006; 110: 354-358.
  • 88 Lip GYH. et al. Oral anticoagulation in atrial fibrillation: A pan-European patient survey. Eur J Intern Med 2007; 18: 202-208.
  • 89 Dantas GC. et al. Patients’ perspectives on taking warfarin: qualitative study in family practice. BMC Fam Pract 2004; 5: 15
  • 90 Department of Health. Patient and public involvement in the new NHS. London: Department of Health, 1999
  • 91 Gage BF. et al. Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. J Am Med Assoc 1995; 274: 1839-1845.
  • 92 Gage BF. et al. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med 1996; 156: 1829-1836.
  • 93 Man-Son-Hing M. et al. Warfarin for atrial fibrillation: The patient’s perspective. Arch Intern Med 1996; 156: 1841-1848.
  • 94 Gage BF. et al. Cost-effectiveness of preference-based antithrombotic therapy for patients with non-valvular atrial fibrillation. Stroke 1998; 29: 1083-1091.
  • 95 Sudlow M. et al. A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences. Br J Gen Pract 1998; 48: 1775-1778.
  • 96 Man-Son-Hing M. et al. for the Stroke Prevention in Atrial Fibrillation Investigators. A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: A randomised controlled trial. J Am Med Assoc 1999; 282: 737-743.
  • 97 Howitt A, Armstrong D. Implementing evidence based medicine in general practice: audit and qualitative study of antithrombotic treatment for atrial fibrillation. Br Med J 1999; 318: 1324-1327.
  • 98 Protheroe J. et al. The impact of patients’ preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis. Br Med J 2000; 320: 1380-1384.
  • 99 Thomson R. et al. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet 2000; 355: 956-962.
  • 100 McAlister FA. et al. for the Decision Aid in Atrial Fibrillation (DAAFI) Investigators. Impact of a patient decision aid on care among patients with nonvalvular atrial fibrillation: a cluster randomized trial. CMAJ 2005; 173: 496-501.
  • 101 Thomson RG. et al. A patient decision aid to support shared decision-making on antithrombotic treatment of patients with atrial fibrillation: randomised controlled trial. Qual Saf Health Care 2007; 16: 216-223.
  • 102 Devereaux PJ. et al. Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation; observational study. Br Med J 2001; 323: 1-7.
  • 103 Fuller R. et al. Avoidance hierarchies and preferences for anticoagulation- semi-qualitative analysis of older patients’ views about stroke prevention and the use of warfarin. Age and Ageing 2004; 33: 608-611.
  • 104 Man-Son-Hing M. et al. The effect of qualitative vs. quantitative presentation of probability estimates on patient decision-making: a randomised trial. Health Expectations 2002; 5: 246-255.
  • 105 Holbrook A. et al. Influence of decision aids on patient preferences for anticoagulant therapy: a randomised trial. Can Med Assoc J 2007; 176: 1583-1587.
  • 106 Alonso-Coello P. et al. Values and preferences in oral anticoagulation in patients with atrial fibrillation, physicians’ and patients’ perspectives: Protocol for a two-phase study. BMC Health Services Res 2008; 8: 221-233.
  • 107 Fuller R. et al. Risk communication and older people- understanding of probability and risk information by medical inpatients aged 75 years and older. Age Ageing 2001; 30: 473-476.
  • 108 Aliot E. et al. for the Atrial Fibrillation AWareness And Risk Education (AF AWARE) group [comprising the Atrial Fibrillation Association (AFA), the European Heart Rhythm Association (EHRA), Stroke Alliance for Europe (SAFE), and the World Heart Federation (WHF)]. An international survey of physician and patient understanding, perception, and attitudes to atrial fibrillation and its contribution to cardiovascular disease morbidity and mortality. Europace 2010; 12: 626-633.
  • 109 Cappato R. et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010; 3: 32-38.
  • 110 Blanc JJ. et al. Consensus document on antithrombotic therapy in the setting of electrophysiological procedures. Europace 2008; 10: 513-527.
  • 111 Hussein AA. et al. Radiofrequency ablation of atrial fibrillation under therapeutic international normalized ratio: a safe and efficacious periprocedural anticoagulation strategy. Heart Rhythm 2009; 6: 1425-1429.
  • 112 Schmidt M. et al. Atrial fibrillation ablation in patients with therapeutic international normalized ratios. Pacing Clin Electrophysiol 2009; 32: 995-999.
  • 113 Vardas PE. et al. European Society of Cardiology; European Heart Rhythm Association. 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. Europace 2007; 9: 959-998.
  • 114 Douketis JD. et al. American College of Chest Physicians. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) Suppl 299S-339S.
  • 115 Jamula E. et al. Perioperative anticoagulation in patients having implantation of a cardiac pacemaker or defibrillator: a systematic review and practical management guide. J Thromb Haemost 2008; 6: 1615-1621.
  • 116 Tolosana JM. et al. 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. Eur Heart J 2009; 30: 1880-1884.
  • 117 Lip G. et al. for the European Society of Cardiology Working Group on Thrombosis. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Thromb Haemost 2010; 103: 13-28.
  • 118 Agostoni P. et al. Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures; Systematic overview and meta-analysis of randomized trials. J Am Coll Cardiol 2004; 44: 349-356.
  • 119 Jolly S. 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. Am Heart J 2009; 157: 132-140.
  • 120 Rossini R. et al. Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. Am J Cardiol 2008; 102: 1618-1623.
  • 121 Faxon DP. et al. Consensus Document: Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting. A North-American perspective. Thromb Haemost 2011; 106: 572-584.
  • 122 Bhatt D. 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. J Am Coll Cardiol 2008; 52: 1502-1517.
  • 123 Ansell J. et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 160S-198S.
  • 124 Ananthasubramaniam K. et al. How safely and for how long can warfarin therapy be withheld in prosthetic heart valve patients hospitalized with a major hemorrhage?. Chest 2001; 119: 478-484.
  • 125 Hackman DG. et al. Prognostic implications of warfarin cessation after major trauma. A population-based cohort analysis. Circulation 2005; 111: 2250-2256.
  • 126 Dentali F. et al. Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J Thromb Haemost 2006; 4: 1853-1863.
  • 127 Crowther MA. et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin. Ann Intern Med 2009; 150: 293-300.
  • 128 Crowther MA. 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. Ann Intern Med 2002; 137: 251-254.
  • 129 Lubetsky A. et al. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med 2003; 163: 2469-2473.
  • 130 van Geest-Daalderop JH. et al. Invasive procedures in the outpatient setting: Managing the short-acting acenocoumarol and the long-acting phenprocoumon. Thromb Haemost 2007; 98: 747-755.
  • 131 Aguilar I M. et al. Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion. Mayo Clin Proc 2007; 82: 82-92.
  • 132 van Aart L. 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. Thromb Res 2006; 118: 313-320.
  • 133 Pabinger I. et al. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost 2008; 6: 622-631.
  • 134 Levi M. Disseminated intravascular coagulation. Crit Care Med 2007; 35: 2191-2195.
  • 135 Bonow RO. et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 2006; 48: e1-148.
  • 136 Kanderian AS. et al. Success of Surgical Left Atrial Appendage Closure. Assessment by Transesophageal Echocardiography. J Am Coll Cardiol 2008; 52: 924-929.
  • 137 Ostermayer SH. 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 multicenter feasibility trials. J Am Coll Cardiol 2005; 46: 9-14.
  • 138 Holmes DR, Reddy VY, Turi ZG. et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised noninferiority trial. Lancet 2009; 374: 534-542.
  • 139 Reddy VY. et al. Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011; 123: 417-424.
  • 140 Pengo V. et al. Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation. A consensus document of the Italian Federation of Thrombosis Centers (FCSA). Thromb Haemost 2011; 106: 868-876.
  • 141 Ufer M. Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost 2010; 103: 572-585.
  • 142 Ahrens I. et al. What do the RE-LY, AVERROES and ROCKET-AF trials tell us for stroke prevention in atrial fibrillation?. Thromb Haemost 2011; 105: 574-578.
  • 143 Barrett YC. et al. Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost 2010; 104: 1263-1271.
  • 144 van Ryn J. et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116-1127.
  • 145 Eerenberg ES. et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124: 1573-1579.
  • 146 Winkle RA. et al. The Use of Dabigatran Immediately After Atrial Fibrillation Ablation. J Cardiovasc Electrophysiol 2011 prepub online doi:10.1111/j.1540-8167.2011.02175.x