Vitamin K antagonists in heart disease: Current status and perspectives (Section III): Position paper of the ESC working group on thrombosis - Task force on anticoagulants in heart disease

Thrombosis and Haemostasis

Volumn 110, Issue 6, 2013, Pages 1087-1107

  De Caterina, Raffaele ^a   Husted, Steen ^b   Wallentin, Lars ^c   Andreotti, Felicita ^d   Arnesen, Harald ^e   Bachmann, Fedor ^f   Baigent, Colin ^g   Huber, Kurt ^h   Jespersen, Jørgen ⁱ   Kristensen, Steen Dalby ^b   Lip, Gregory Y H ^j   Morais, João ^k   Rasmussen, Lars Hvilsted ^b   Siegbahn, Agneta ^c   Verheugt, Freek W A ^l   Weitz, Jeffrey I ^m  

^a UNIVERSITY OF CHIETI   (Italy)

^b AARHUS UNIVERSITY HOSPITAL   (Denmark)

^c UPPSALA UNIVERSITY   (Sweden)

^d CATHOLIC UNIVERSITY   (Italy)

^e ULLEVÅL UNIVERSITY HOSPITAL   (Norway)

^f UNIVERSITY OF LAUSANNE   (Switzerland)

^g UNIVERSITY OF OXFORD   (United Kingdom)

^h Wilhelminenhospital   (Austria)

ⁱ UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^j CITY HOSPITAL   (United Kingdom)

^k Leiria Hospital   (Portugal)

^l RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^m HAMILTON GENERAL HOSPITAL   (Canada)

more..

Author keywords

Coagulation; Coronary heart disease, atrial fibrillation, artificial heart valves, heart failure; Oral anticoagulants; Vitamin K antagonists

Indexed keywords

1, 3 INDANDIONE DERIVATIVE; ACENOCOUMAROL; ACETYLSALICYLIC ACID; AMIODARONE; ANTIBIOTIC AGENT; ANTIDEPRESSANT AGENT; ANTIFUNGAL AGENT; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; APIXABAN; ASCUMAR; BLOOD CLOTTING FACTOR 10; BLOOD CLOTTING FACTOR 7; BLOOD CLOTTING FACTOR 9; CLOPIDOGREL; COUMARIN; DABIGATRAN; FALITHIOM; FENCUMAR; FENINDION; FLUINDIONE; LAWARIN; LOW MOLECULAR WEIGHT HEPARIN; MARCUPHEN; MENAQUINONE; PARACETAMOL; PHENINDIONE; PHENPROCOUMON; PHYTOMENADIONE; PLACEBO; PROTHROMBIN; RIVAROXABAN; ROSUVASTATIN; SIMVASTATIN; TECARFARIN; THROMBOPLASTIN; UNCLASSIFIED DRUG; WARFANT; WARFARIN;

ACUTE CORONARY SYNDROME; BLEEDING; CEREBROVASCULAR ACCIDENT; CORONARY ARTERY BYPASS GRAFT; CREATININE CLEARANCE; DRUG MECHANISM; DRUG MEGADOSE; GENOTYPE; HEART ATRIUM FIBRILLATION; HEART DISEASE; HEART FAILURE; HUMAN; ISCHEMIC HEART DISEASE; KIDNEY FUNCTION; LOW DRUG DOSE; MECHANICAL HEART VALVE; META ANALYSIS (TOPIC); MITRAL VALVE DISEASE; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTHROMBIN TIME; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK FACTOR; SELF CARE; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSTHORACIC ECHOCARDIOGRAPHY;

ARTIFICIAL HEART VALVES; ATRIAL FIBRILLATION; COAGULATION; CORONARY HEART DISEASE; HEART FAILURE; ORAL ANTICOAGULANTS; VITAMIN K ANTAGONISTS;

ADVISORY COMMITTEES; ANTICOAGULANTS; BLOOD COAGULATION; CARDIOLOGY; EUROPE; HEART DISEASES; HUMANS; SOCIETIES, MEDICAL; THROMBOSIS; VITAMIN K;

EID: 84888400659     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH13-06-0443     Document Type: Review

References (187)

1. Nutrition classics from The Journal of Biological Chemistry 138: 21-33, 1941. Studies on the hemorrhagic sweet clover disease. IV. The isolation and crystallization of the hemorrhagic agent by Harold A. Campbell and Karl Paul Link. Nutr Rev 1974; 32: 244-246.
2. De Caterina R, et al. 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. Thromb Haemost 2013; 109: 769-786.
3. De Caterina R, et al. 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. Thromb Haemost 2013; 109: 769-786.
4. Patrono C, et al. Antiplatelet agents for the treatment and prevention of atherothrombosis. Eur Heart J 2011; 32: 2922-2932.
5. De Caterina R, et al. Anticoagulants in heart disease: current status and perspectives. Eur Heart J 2007; 28: 880-913.
6. De Caterina R, et al. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease Position Paper. J Am Coll Cardiol 2012; 59: 1413-1425.
7. 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-98S.
8. Kirchhof P, Ammentorp B, Darius H, et al. Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation (PREFER in AF). Europace 2013; in press.
9. Moridani M, et al. Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large anticoagulant clinic cohort. Clin Biochem 2006; 39: 606-612.
10. Higashi MK, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. J Am Med Assoc 2002; 287: 1690-1698.
11. Limdi NA, et al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood 2010; 115: 3827-3834.
12. Klein TE, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360: 753-764.
13. Ferder NS, et al. Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy. J Thromb Haemost 2010; 8: 95-100.
14. Horne BD, et al. Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy. Thromb Haemost 2012; 107: 232-240.
15. Skov J, et al. The influence of VKORC1 and CYP2C9 gene sequence variants on the stability of maintenance phase warfarin treatment. Thromb Res 2013; 131: 125-129.
16. Liang R, et al. Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients. J Thromb Thrombolysis 2012; 34: 120-125.
17. Loebstein R, et al. A coding VKORC1 Asp36Tyr polymorphism predisposes to warfarin resistance. Blood 2007; 109: 2477-2480.
18. van Schie RM, et al. Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data. Eur Heart J 2011; 32: 1909-1917.
19. Geisen C, et al. Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters. Eur J Clin Pharmacol 2011; 67: 371-381.
20. van Schie RM, et al. Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose. Pharmacogenomics 2012; 13: 1917-1923.
21. Verhoef TI, et al. Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users. J Thromb Haemost 2012; 10: 606-614.
22. Cerezo-Manchado JJ, et al. Creating a genotype-based dosing algorithm for acenocoumarol steady dose. Thromb Haemost 2013; 109: 146-153.
23. Borobia AM, et al. An acenocoumarol dosing algorithm using clinical and pharmacogenetic data in Spanish patients with thromboembolic disease. PLoS One 2012; 7: e41360.
24. van Schie RM, et al. An evaluation of gene-gene interaction between the CYP2C9 and VKORC1 genotypes affecting the anticoagulant effect of phenprocoumon and acenocoumarol. J Thromb Haemost 2012; 10: 767-772.
25. Lacut K, et al. Impact of genetic factors (VKORC1, CYP2C9, CYP4F2 and EPHX1) on the anticoagulation response to fluindione. Br J Clin Pharmacol 2012; 73: 428-436.
26. Johnson EG, et al. Genotype-based dosing algorithms for warfarin therapy: data review and recommendations. Mol Diagn Ther 2011; 15: 255-264.
27. Anderson JL, et al. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation 2012; 125: 1997-2005.
28. Eriksson N, Wadelius M. Prediction of warfarin dose: why, when and how? Pharmacogenomics 2012; 13: 429-440.
29. Lurie Y, et al. Warfarin and vitamin K intake in the era of pharmacogenetics. Br J Clin Pharmacol 2010; 70: 164-170.
30. Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ 2007; 177: 369-371.
31. Simonson SG, et al. Effect of rosuvastatin on warfarin pharmacodynamics and pharmacokinetics. J Clin Pharmacol 2005; 45: 927-934.
32. Andersson ML, et al. A clinically significant interaction between warfarin and simvastatin is unique to carriers of the CYP2C9*3 allele. Pharmacogenomics 2012; 13: 757-762.
33. Skov J, et al. Plenty of pills: polypharmacy prevails in patients of a Danish anticoagulant clinic. Eur J Clin Pharmacol 2011; 67: 1169-1174.
34. Skov J, et al. Perceived stress predicts the stability of vitamin K-antagonist treatment of anticoagulant clinic patients. Thromb Haemost 2012; 108: 581-582.
35. Requirements for thromboplastins and plasma used to control oral anticoagulant therapy (Requirements for Biological Substances no. 30, revised 1982). In: WHO Expert Committee on Biological Standardization. Thirty-Third report. Annex 3, WHO Technical Report Series, no. 687 Geneva: World Health Organization, 1983. 687: 1-184.
36. Guidelines for thromboplastins and plasma used to control oral anticoagulant therapy. In: WHO Expert Committee on Biological Standardization. Forty-Eight Report. Annex 3. WHO Technical Report Series n. 889: i-vi, 1-111.
37. Poller L. Progress in standardisation in anticoagulant control. Hematol Rev 1987; 1: 225-241.
38. Poller L. International Normalized Ratios (INR): the first 20 years. J Thromb Haemost 2004; 2: 849-860.
39. Kirkwood TB. Calibration of reference thromboplastins and standardisation of the prothrombin time ratio. Thromb Haemost 1983; 49: 238-244.
40. Ansell J, et al. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 204S-233S.
41. Poggio M, et al. The effect of some instruments for prothrombin time testing on the International Sensitivity Index (ISI) of two rabbit tissue thromboplastin reagents. Thromb Haemost 1989; 62: 868-874.
42. Peters RH, et al. A Multi-centre study to evaluate method dependency of the international sensitivity index of bovine thromboplastin. Thromb Haemost 1989; 61: 166-169.
43. Ray MJ, Smith IR. The dependence of the International Sensitivity Index on the coagulometer used to perform the prothrombin time. Thromb Haemost 1990; 63: 424-429.
44. van den Besselaar AMHP, et al. Influence of three types of automated coagulometers on the international sensitivity index (ISI) of rabbit, human, and recombinant human tissue factor preparations--a multicenter study. Thromb Haemost 1999; 81: 66-70.
45. Clarke K, et al. Assessment of value of calibrated lyophilised plasmas to determine International Sensitivity Index for coagulometers. J Clin Pathol 1992; 45: 58-60.
46. van den Besselaar AMHP, et al. Guidelines on preparation, certification, and use of certified plasmas for ISI calibration and INR determination. J Thromb Haemost 2004; 2: 1946-1953.
47. Poller L, et al. Simplified method for international normalized ratio (INR) derivation based on the prothrombin time/INR line: an international study. Clin Chem 2010; 56: 1608-1617.
48. Poller L, et al. INR derivation with the PT/INR Line simplified using a spreadsheet from the world wide web. J Clin Pathol 2011; 64: 930-932.
49. Houbouyan LL, Goguel AF. Long-term French experience in INR standardization by a procedure using plasma calibrants. Am J Clin Pathol 1997; 108: 83-89.
50. Clinical and Laboratory Standards Institute. Procedures for Validation of INR and Local Calibration of PT/INR Systems; Approved Guideline. 2005; 25.
51. Poller L, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost 2008; 6: 935-943.
52. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
53. Granger CB, et al. for the ARISTOTLE Committees and Investigators. Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011; 365: 981-992.
54. Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-889.
55. Poller L, et al. Phase III studies on novel oral anticoagulants for stroke prevention in atrial fibrillation: a look beyond the excellent results: a rebuttal. J Thromb Haemost 2013; 11: 1203-1205.
56. Poller L, et al. Multicentre randomised study of computerised anticoagulant dosage. European Concerted Action on Anticoagulation. Lancet 1998; 352: 1505-1509.
57. Samama M, et al. Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemost 1984; 51: 132-133.
58. Rosenzweig N, et al. Activated protein C concentrate treatment for skin necrosis under warfarin treatment in severe genetic protein C deficiency combined with prothrombin mutation and factor V Leiden. Thromb Haemost 2009; 101: 405-407.
59. Vigano D'Angelo S, et al. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest 1986; 77: 416-425.
60. Rosendaal FR, et al. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-239.
61. Schulman S, et al. Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. Ann Intern Med 2011; 155: 653-659, W201-203.
62. Apostolakis S, et al. Factors affecting quality of anticoagulation control amongst atrial fibrillation patients on warfarin: The SAMe-TT2R2 score. Chest 2013; epub ahead of print doi: 10. 1378/chest. 13-0054.
63. Njaastad AM, et al. Gains and losses of warfarin therapy as performed in an anticoagulation clinic. J Intern Med 2006; 259: 296-304.
64. Poller L, et al. Screening computer-assisted dosage programs for anticoagulation with warfarin and other vitamin K-antagonists: minimum safety requirements for individual programs. On behalf of the Subcommittee on Control of Anticoagulation of the Scientific and Standardisation Committee of the ISTH. J Thromb Haemost 2009; 7: 1736.
65. Poller L. Precision and accuracy of CoaguChek S and XS monitors: the need for external quality assessment. Thromb Haemost 2009; 101: 419-421.
66. Jespersen J, et al. External quality assessment (EQA) for CoaguChek monitors. Thromb Haemost 2010 103: 936-941.
67. Hylek EM, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349: 1019-1026.
68. Hylek EM, et al. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996; 335: 540-546.
69. Tripodi A, et al. Determination of the International Sensitivity Index of a new near-patient testing device to monitor oral anticoagulant therapy--overview of the assessment of conformity to the calibration model. Thromb Haemost 1997; 78: 855-858.
70. Poller L, et al. European concerted action on anticoagulation. Quality assessment of the CoaguChek Mini and TAS PT-NC point-of-care whole-blood prothrombin time monitors. Clin Chem 2004; 50: 537-544.
71. Meijer P, et al. A national field study of quality assessment of CoaguChek pointof-care testing prothrombin time monitors. Am J Clin Pathol 2006; 126: 756-761.
72. Poller L, et al. Quality assessment of CoaguChek point-of-care prothrombin time monitors: comparison of the European community-approved procedure and conventional external quality assessment. Clin Chem 2006; 52: 1843-1847.
73. Christensen TD, Larsen TB. Precision and accuracy of point-of-care testing coagulometers used for self-testing and self-management of oral anticoagulation therapy. J Thromb Haemost 2012; 10: 251-260.
74. Heneghan C, et al. Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet 2006; 367: 404-411.
75. The Cochrane Collaboration. Self-monitoring and self-management of oral anticoagulation. The Cochrane Library 2012 4: Available at: http://www. the cochranelibrary. com.
76. Gadisseur APA, et al. Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial. Arch Intern Med 2003; 163: 2639-2646.
77. Siebenhofer A, et al. Systematic review of studies of self-management of oral anticoagulation. Thromb Haemost 2004; 91: 225-232.
78. Matchar DB, et al. Effect of home testing of international normalized ratio on clinical events. N Engl J Med 2010; 363: 1608-1620.
79. Gadisseur APM, et al. Patient self-management of oral anticoagulant care vs. management by specialized anticoagulation clinics: positive effects on quality of life. J Thromb Haemost 2004; 2: 584-591.
80. Heneghan C, et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet 2012; 379: 322-334.
81. Albers GW, et al. Antithrombotic therapy in atrial fibrillation. Chest 2001; 119: 194S-206S.
82. Connolly SJ, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991; 18: 349-355.
83. The Stroke Prevention in Atrial Fibrillation Investigators. Bleeding during antithrombotic therapy in patients with atrial fibrillation. Arch Intern Med 1996; 156: 409-416.
84. 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.
85. Levine MN, et al. Hemorrhagic complications of anticoagulant treatment. Chest 1998; 114: 511S-523S.
86. Hart RG, et al. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999; 30: 1223-1229.
87. Petersen P, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet 1989; 333: 175-179.
88. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990; 323: 1505-1511.
89. The Stroke Prevention in Atrial Fibrillation Study Investigators. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991; 84: 527-539.
90. Ezekowitz MD, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med 1992; 327: 1406-1412.
91. Frykman V, et al. Management of atrial fibrillation: discrepancy between guideline recommendations and actual practice exposes patients to risk for complications. Eur Heart J 2001; 22: 1954-1959.
92. Ellis DJ, et al. The first evaluation of a novel vitamin K antagonist, tecarfarin (ATI-5923), in patients with atrial fibrillation. Circulation 2009; 120: 1029-1035, 2 p following 35.
93. Freedman JE, Gersh BJ. New therapies for stroke prevention in atrial fibrillation: the long road to enhanced efficacy. Circulation 2009; 120: 1024-1026.
94. The Medical Research Council's General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998; 351: 233-241.
95. Smith P, et al. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 323: 147-152.
96. Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group. Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet 1994; 343: 499-503.
97. Hurlen M, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347: 969-974.
98. van Es RF, et al. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002; 360: 109-113.
99. Cohen M, et al. Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). Am J Cardiol 1990; 66: 1287-1292.
100. Cohen M, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation 1994; 89: 81-88.
101. Coumadin Aspirin Reinfarction Study (CARS) Investigators. Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet 1997; 350: 389-396.
102. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. J Am Coll Cardiol 2001; 37: 475-484.
103. Fiore LD, et al. Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation 2002; 105: 557-563.
104. Brouwer MA, et al. Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. Circulation 2002; 106: 659-665.
105. Herlitz J, et al. Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. Eur Heart J 2004; 25: 232-239.
106. Andreotti F, et al. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25 307 patients. Eur Heart J 2006; 27: 519-526.
107. Yusuf S, et al. 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.
108. Knatterud GL, et al. Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial. Post CABG Investigators. Circulation 2000; 102: 157-165.
109. ten Berg JM, et al. Effect of coumarins started before coronary angioplasty on acute complications and long-term follow-up: a randomized trial. Circulation 2000 102: 386-391.
110. Hall P, et al. A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasoundguided stent implantation. Circulation 1996; 93: 215-222.
111. Schömig A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996; 334: 1084-1089.
112. Leon MB, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998; 339: 1665-1671.
113. Bertrand ME, et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation 1998; 98: 1597-1603.
114. Urban P, et al. Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation 1998; 98: 2126-2132.
115. Van de Werf F, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am Heart J 2012; 163: 931-937 e1.
116. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013; 369: 1206-1214.
117. Hart RG for the Stroke Risk in Atrial Fibrilattion Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007; 69: 546-554.
118. Hughes M, Lip GYH. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 2008; 99: 295-304.
119. Frost L, et al. Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation. Am J Med 2000; 108: 36-40.
120. Lin L-Y, et al. Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation-A nationwide database analysis. Atherosclerosis 2011; 217: 292-295.
121. Olesen JB, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. Br Med J 2011; 342: d124.
122. Rasmussen LH, et al. Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health cohort study. J Thromb Haemost 2011; 9: 1301-1307.
123. Ezekowitz MD, et al. Silent cerebral infarction in patients with nonrheumatic atrial fibrillation. The Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. Circulation 1995; 92: 2178-2182.
124. Petersen P, et al. Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Arch Intern Med 1990; 150: 819-821.
125. 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.
126. Karthikeyan G, Eikelboom JW. The CHADS2 score for stroke risk stratification in atrial fibrillation--friend or foe? Thromb Haemost 2010; 104: 45-48.
127. 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). Eur Heart J 2010; 31: 2369-2429.
128. Lip GYH, 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.
129. Van Staa TP, et al. A comparison of risk stratification schemes for stroke in 79, 884 atrial fibrillation patients in general practice. J Thromb Haemost 2011; 9: 39-48.
130. Olesen JB, et al. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study. Thromb Haemost 2012; 107: 1172-1179.
131. Camm AJ, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747 and corrigenda Eur Heart J 2013; doi: 10. 1093/eurheartj/eht027 and do: 10. 1093/eurheartj/eht291.
132. Hart RG, et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
133. The Stroke Prevention in Atrial Fibrillation investigators. A differential effect of aspirin in prevention of stroke on atrial fibrillation. J Stroke Cerebrovasc Dis 1993; 3: 181-188.
134. Sato H, et al. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke 2006; 37: 447-451.
135. Mant J, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
136. Connolly SJ, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360: 2066-2078.
137. Connolly SJ, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-817.
138. Lip GYH, et al. Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary--a Consensus Document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2010; 31: 1311-1318.
139. Lip GYH, et al. 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.
140. Faxon DP, et al. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: a North American perspective: executive summary. Circ Cardiovasc Interv 2011; 4: 522-534.
141. Huber K, et al. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: similarities and dissimilarities between North America and Europe. Thromb Haemost 2011; 106: 569-571.
142. Cairns JA, et al. 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.
143. Tay KH, et al. Bleeding risks with combination of oral anticoagulation plus antiplatelet therapy: is clopidogrel any safer than aspirin when combined with warfarin? Thromb Haemost 2008; 100: 955-957.
144. 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.
145. Lip GYH, et al. 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. Thromb Haemost 2011; 106: 997-1011.
146. Pisters R, 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. Chest 2010; 138: 1093-1100.
147. 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.
148. Apostolakis S, et al. Performance of the HEMORR2HAGES, ATRIA, and HASBLED bleeding risk-prediction scores in patients with atrial fibrillation under-going anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. J Am Coll Cardiol 2012; 60: 861-867.
149. Lip GYH, et al. Assessing the risk of bleeding in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation project. Circ Arrhythm Electrophysiol 2012; 5: 941-948.
150. Roldan V, et al. Predictive value of the HAS-BLED and ATRIA bleeding scores for the risk of serious bleeding in a "real-world" population with atrial fibrillation receiving anticoagulant therapy. Chest 2013; 143: 179-184.
151. Guo Y, et al. Validation of contemporary stroke and bleeding risk stratification scores in non-anticoagulated Chinese patients with atrial fibrillation. Int J Cardiol 2013; 168: 904-909.
152. Apostolakis S, et al. Performance of the HEMORR 2 HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in nonwarfarin anticoagulated atrial fibrillation patients. J Am Coll Cardiol 2013; 61: 386-387.
153. Omran H, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012; 108: 65-73.
154. Smith JG, et al. Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score. EuroIntervention 2012; 8: 672-678.
155. Lip GYH, et al. Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes, for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study. Int J Cardiol 2013; 168: 414-419.
156. 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: 739-749.
157. Friberg L, et al. Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012; 125: 2298-2307.
158. Banerjee A, et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a 'real world' atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107: 584-589.
159. Szekely P. Systemic Embolism and Anticoagulant Prophylaxis in Rheumatic Heart Disease. Br Med J 1964; 1: 1209-1212.
160. Chiang CW, et al. Predictors of systemic embolism in patients with mitral stenosis. A prospective study. Ann Intern Med 1998; 128: 885-889.
161. Whitlock RP, et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e576S-600S.
162. Vahanian A, 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. Eur Heart J 2007; 28: 230-268.
163. Vahanian A, et al. Guidelines on the management of valvular heart disease (version 2012). The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2012; 33: 2451-2496.
164. Butchart EG, et al. Recommendations for the management of patients after heart valve surgery. Eur Heart J 2005; 26: 2463-2471.
165. Butchart E, De Caterina R. Antithrombotic management in patients with prosthetic valves. In: Therapeutic Advances in Thrombosis. Wiley-Blackwell; 2013.
166. Bonow RO, et al. 2008 focused update incorporated into the 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). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52: e1-142.
167. Camm AJ, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation--developed with the special contribution of the European Heart Rhythm Association. Europace 2012; 14: 1385-1413.
168. Lamberts M, et al. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation 2012; 126: 1185-1193.
169. Lip GYH, et al. Thromboembolism and antithrombotic therapy for heart failure in sinus rhythm: an executive summary of a joint consensus document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Thromb Haemost 2012; 108: 1009-1022.
170. Snowden S, Silus L. Oral anticoagulation with warfarin for patients with left ventricular systolic dysfunction. Cardiol Rev 2011; 19: 36-40.
171. De Lorenzo F, et al. Blood coagulation in patients with chronic heart failure: evidence for hypercoagulable state and potential for pharmacological intervention. Drugs 2003; 63: 565-576.
172. Stratton JR, Resnick AD. Increased embolic risk in patients with left ventricular thrombi. Circulation 1987; 75: 1004-1011.
173. Cregler LL. Antithrombotic therapy in left ventricular thrombosis and systemic embolism. Am Heart J 1992; 123: 1110-1114.
174. Turpie AG, et al. Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N Engl J Med 1989; 320: 352-357.
175. Falk RH, et al. Ventricular thrombi and thromboembolism in dilated cardiomyopathy: a prospective follow-up study. Am Heart J 1992; 123: 136-142.
176. Massie BM, et al. The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics. J Card Fail 2004; 10: 101-112.
177. Massie BM, et al. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation 2009; 119: 1616-1624.
178. Califf RM. Watching the WATCH trial: the role of sponsors and data monitoring committees. J Card Fail 2004; 10: 113-114.
179. Cleland JGF, et al. The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. Am Heart J 2004; 148: 157-164.
180. Cokkinos DV, et al. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail 2006; 8: 428-432.
181. Homma S, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012 366: 1859-1869.
182. Ansell J. New oral anticoagulants should not be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation. Circulation 2012; 125: 165-170; discussion by Granger CB, Armaganijan LV 170.
183. Christensen TD, et al. Letter by Christensen et al. regarding article, "New oral anticoagulants should not be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation". Circulation 2012; 126: e45; author reply e46.
184. Poller L, et al. The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers--two independent studies. J Thromb Haemost 2011; 9: 140-148.
185. Mentré F, et al. Population pharmacokinetic-pharmacodynamic analysis of fluindione in patients. Clin Pharmacol Ther 1998; 63: 64-78.
186. Ufer M. Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet 2005; 44: 1227-1246.
187. Comets E, et al. Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians. Clin Pharmacol Ther 2012; 91: 777-786.