Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents

Europace

Volumn 14, Issue 3, 2012, Pages 312-324

  Bassand, Jean Pierre ^a  

^a UNIVERSITY HOSPITAL JEAN MINJOZ   (France)

Author keywords

Anticoagulants; Apixaban; Aspirin; Atrial fibrillation; Clopidogrel; Dabigatran; Drug discovery; Rivaroxaban; Stroke; Warfarin

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; APIXABAN; AZD 837; BETRIXABAN; CLOPIDOGREL; DABIGATRAN; DABIGATRAN ETEXILATE; DAREXABAN; EDOXABAN; FLUINDIONE; IDRABIOTAPARINUX; IDRAPARINUX; INDOBUFEN; PLACEBO; RIVAROXABAN; THROMBIN INHIBITOR; TRIFLUSAL; UNCLASSIFIED DRUG; WARFARIN; XIMELAGATRAN;

ANTICOAGULANT THERAPY; BLEEDING; BRAIN EMBOLISM; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CONSTIPATION; DIARRHEA; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DYSPEPSIA; EMBOLISM; EXTRACRANIAL BLEEDING; EXTRACRANIAL HEMORRHAGE; GASTROINTESTINAL HEMORRHAGE; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; LIVER TOXICITY; LOW DRUG DOSE; NAUSEA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; REVIEW; RISK ASSESSMENT; SECONDARY PREVENTION; STROKE; THROMBOEMBOLISM; THROMBOSIS PREVENTION; TRANSIENT ISCHEMIC ATTACK; VENOUS THROMBOEMBOLISM;

ANTICOAGULANTS; ANTITHROMBINS; ATRIAL FIBRILLATION; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; FACTOR XA; FEMALE; HUMANS; MALE; PLATELET AGGREGATION INHIBITORS; RISK; STROKE; TREATMENT OUTCOME; VITAMIN K;

EID: 84857861298     PISSN: 10995129     EISSN: 15322092     Source Type: Journal    
DOI: 10.1093/europace/eur263     Document Type: Review

References (82)

1. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV et al. Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm management and stroke prevention: The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-5. (Pubitemid 32424106)
2. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. ACC/ AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation- full text. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace 2006;8:651-745. (Pubitemid 44472247)
3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22:983-8.
4. Stroke Risk in Atrial Fibrillation Working Group. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke 2008;39:1901-10.
5. Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians evidencebased clinical practice guidelines (8th Edition). Chest 2008;133:546S-92S. (Pubitemid 351892972)
6. Lip GY, Nieuwlaat R, Pisters R, Lane D, Crijns H. 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; 137:263-72.
7. Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: Nationwide cohort study. BMJ 2011;342:d124.
8. van Staa TP, Setakis E, Di Tanna GL, Lane DA, Lip GY. A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. J Thromb Haemost 2011;9:39-48.
9. Tang RB, Dong JZ, Liu XP, Long DY, Yu RH, Du X et al. Is CHA2DS2-VASc score a predictor of left atrial thrombus in patients with paroxysmal atrial fibrillation? Thromb Haemost 2011;105:1107-9.
10. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S 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.
11. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2011;123:e269-e367.
12. Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M. 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.
13. Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689-96. (Pubitemid 46842784)
14. Lip GY, Frison L, Halperin JL, Lane DA. 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;57:173-80.
15. Olesen JB, Lip GY, Hansen PR, Lindhardsen J, Ahlehoff O, Andersson C 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;9:1460-7.
16. Gage BF, Yan Y, Milligan PE, Waterman AD, Culverhouse R, Rich MW et al. Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006;151:713-9. (Pubitemid 43290267)
17. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146:857-67. (Pubitemid 351650486)
18. Gurwitz JH, Field TS, Judge J, Rochon P, Harrold LR, Cadoret C et al. The incidence of adverse drug events in two large academic long-term care facilities. Am J Med 2005;118:251-8. (Pubitemid 40312636)
19. Flaherty ML, Kissela B,Woo D, Kleindorfer D, Alwell K, Sekar P et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007;68:116-21. (Pubitemid 46071894)
20. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. 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. (Pubitemid 351892967)
21. Waldo AL, Becker RC, Tapson VF, Colgan KJ, for the NABOR Steering Committee. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol 2005;46:1729-36. (Pubitemid 41531631)
22. Boulanger L, Kim J, Friedman M, Hauch O, Foster T, Menzin J. Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with nonvalvular atrial fibrillation in clinical practice. Int J Clin Pract 2006;60:258-64. (Pubitemid 43337604)
23. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA III et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;123:104-23.
24. Stroke Prevention in Atrial Fibrillation Investigators. Stroke Prevention in Atrial Fibrillation study. Final results. Circulation 1991;84:527-39.
25. Sato H, Ishikawa K, Kitabatake A, Ogawa S, Maruyama Y, Yokota Y et al. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke 2006;37:447-51. (Pubitemid 43732003)
26. Choudhury A, Lip GY. Atrial fibrillation and the hypercoagulable state: From basic science to clinical practice. Pathophysiol Haemost Thromb 2003;33:282-9. (Pubitemid 40278696)
27. ACTIVE Writing Group 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 (ACTIVE W): A randomised controlled trial. Lancet 2006;367:1903-12.
28. The ACTIVE Investigators. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360:2066-78.
29. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996;348:633-8.
30. Landefeld CS, Anderson PA, Goodnough LT, Moir TW, Hom DL, Rosenblatt MW et al. The bleeding severity index: Validation and comparison to other methods for classifying bleeding complications of medical therapy. J Clin Epidemiol 1989;42: 711-8. (Pubitemid 19213115)
31. Gullov AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J et al. Fixed minidose warfarin and aspirin alone and in combination vs. adjusteddose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch Intern Med 1998;158: 1513-21. (Pubitemid 28340984)
32. Edvardsson N, Juul-Moller S, Omblus R, Pehrsson K. Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation. J Intern Med 2003;254:95-101. (Pubitemid 36819134)
33. Lechat P, Lardoux H, Mallet A, Sanchez P, Derumeaux G, Lecompte T et al. Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontané; FFAACS). Cerebrovasc Dis 2001;12:245-52. (Pubitemid 32973957)
34. Pérez-Gómez F, Alegría E, Berjón J, Iriarte JA, Zumalde J, Salvador A et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: A randomized multicenter study. J Am Coll Cardiol 2004;44:1557-66. (Pubitemid 39377708)
35. Bover R, Pérez-Gómez F, Maluenda MP, Asenjo S, Pérez-Saldaña R, Igea A et al. Long-term follow-up of atrial fibrillation patients in the NASPEAF study. Prospective evaluation of different antiplatelet treatments. Rev Esp Cardiol 2009;62: 992-1000.
36. Flaker GC, Gruber M, Connolly SJ, Goldman S, Chaparro S, Vahanian A et al. Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: An exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Am Heart J 2006;152: 967-73. (Pubitemid 44637136)
37. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361: 1139-51.
38. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified events in the RE-LY trial. N Engl J Med 2010;363:1875-6.
39. The Executive Steering Committee on behalf of the ROCKET AF Study Investigators. Rivaroxaban-Once daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: Rationale and Design of the ROCKET AF study. Am Heart J 2010;159:340-7.
40. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91.
41. Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD et al. Apixaban for Reduction In Stroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial: Design and rationale. Am Heart J 2010;159:331-9.
42. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365:981-92.
43. Eikelboom JW, O'Donnell M, Yusuf S, Diaz R, Flaker G, Hart R et al. Rationale and design of AVERROES: Apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment. Am Heart J 2010;159:348-53.
44. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-17.
45. Ruff CT, Giugliano RP, Antman EM, Crugnale SE, Bocanegra T, Mercuri M et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation- Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). Am Heart J 2010;160:635-41.
46. Lee WM, Larrey D, Olsson R, Lewis JH, Keisu M, Auclert L et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf 2005;28:351-70. (Pubitemid 40545769)
47. AstraZeneca. AstraZeneca decides to withdraw ExantaTM. 2006. http://www. astrazeneca.com/Media/Press-releases/Article/20060214-AstraZeneca-Decidesto- Withdraw-Exanta (January 2012, date last accessed).
48. Albers GW, Diener HC, Frison L, Grind M, Nevinson M, Partridge S et al. Ximelagatran vs. warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: A randomized trial. JAMA 2005;293:690-8.
49. Olsson SB, Executive Steering Committee of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): Randomised controlled trial. Lancet 2003;362:1691-8. (Pubitemid 37468318)
50. Karthikeyan G, Eikelboom JW, Hirsh J. New oral anticoagulants: Not quite there yet. Pol Arch Med Wewn 2009;119:53-8.
51. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008;36:386-99. (Pubitemid 351185753)
52. Stangier J, Rathgen K, Stahle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007;64:292-303. (Pubitemid 47283865)
53. Boehringer Ingelheim Pharmaceuticals I. Press release: FDA approves pradaxa, marking a major milestone to reduce the risk of stroke in patients with non-valvular atrial fibrillation. 2010. http://us.boehringer-ingelheim.com/ news-events/press-releases/press-release-archive/2010/october-20-2010.html (January 2012, date last accessed).
54. Medpage Today. Dabigatran: The Case of the Missing 110-mg Dose. 2010. http:// www.medpagetoday.com/Cardiology/Arrhythmias/22906 (January 2012, date last accessed).
55. Wann LS, Curtis AB, Ellenbogen KA, Estes NA III, Ezekowitz MD, Jackman WM et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;123:1144-50.
56. Medical News Today. PRADAXTM (dabigatran etexilate) gains approval in Canada for stroke prevention In atrial fibrillation. 2010. http://www. medicalnewstoday. com/releases/205933.php (January 2012, date last accessed).
57. Boehringer Ingelheim. Breakthrough therapy PRADAXAw (dabigatran etexilate) first drug in 50 years to gain approval for stroke prevention in atrial fibrillation in EU. 2011. http://www.boehringer-ingelheim.com/news/news- releases/press-releases/2011/04-aug-2011-dabigatranetexilate.html (January 2012, date last accessed).
58. Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S et al. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: A subgroup analysis of the RE-LY trial. Lancet Neurol 2010;9:1157-63.
59. Roskell NS, Lip GY, Noack H, Clemens A, Plumb JM. Treatments for stroke prevention in atrial fibrillation: A network meta-analysis and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2010;104:1106-15.
60. PradaxaTM (dabigatran etexilate) EU summary of product characteristics. Last updated 23 August 2011. Marketing authorization holder: Boehringer Ingelheim International GmbH, D-55216 Ingelheim am Rhein, Germany. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/ 000829/human-med-000981.jsp&mid=WC0b01ac058001d124 (January 2012, date last accessed).
61. Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: A randomized doseguiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J 2009;30:2897-907.
62. Olsson SB, Rasmussen LH, Tveit A, Jensen E, Wessman P, Panfilov S et al. Safety and tolerability of an immediate-release formulation of the oral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Thromb Haemost 2010;103:604-12.
63. Kubitza D, Becka M, Voith B, Zuehlsdorf M,Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct Factor Xa inhibitor. Clin Pharmacol Ther 2005;78:412-21. (Pubitemid 41393676)
64. Kubitza D, Becka M,Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939-an oral, direct Factor Xa inhibitor- after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005;61: 873-80. (Pubitemid 41803696)
65. Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 2008;24:2757-65.
66. Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct Factor Xa inhibitor, in rats, dogs and humans. Drug Metab Dispos 2009;37:1056-64.
67. Perzborn E, Roehrig S, Straub A, Kubitza D, Misselwitz F. The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor. Nat Rev Drug Discov 2011;10:61-75.
68. Food and Drug Administration. FDA approves Xarelto to prevent stroke in people with common type of abnormal heart rhythm. 2011. http://www.fda.gov/ NewsEvents/ Newsroom/PressAnnouncements/ucm278646.htm (January 2012, date last accessed).
69. Reuters News. Bayer wins EU approval for stroke drug Xarelto. 2012. http:// www.reuters.com/article/2011/12/19/bayer-xarelto-idUSWEA613920111219 (January 2012, date last accessed).
70. Hacke W, Hankey G, for the ROCKET-AF Executive and Writing Committee. Rivaroxaban versus warfarin in patients with AF and prior cerebrovascular disease: Results from the ROCKET-AF trial. Cerebrovasc Dis 2011;31(Suppl.2):17 [abstract].
71. Medscape. Rivaroxaban effective for secondary stroke prevention in AF. 2011. http:// www.medscape.com/viewarticle/743544 (January 2012, date last accessed).
72. Fox KAA, Piccini JP, Wojdyla D, Becker RC, Halperin JL, Nessel CC et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J 2011;32:2387-94.
73. XareltoTM (rivaroxaban) EU summary of product characteristics. Last updated 20 January 2012. Marketing authorization holder: Bayer Pharma AG, 13342 Berlin, Germany http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/ human/ medicines/000944/human-med-001155.jsp&mid=WC0b01ac058001d124 (January 2012, date last accessed).
74. Wong PC, Pinto DJ, Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis 2011;31:478-92.
75. Carreiro J, Ansell J. Apixaban, an oral direct Factor Xa inhibitor: Awaiting the verdict. Expert Opin Investig Drugs 2008;17:1937-45.
76. Astellas Pharma Inc. Astellas Pharma Inc. discontinues development of Darexaban (YM150), an oral direct Factor Xa inhibitor. 2011. http://www.astellas.com/en/ corporate/news/detail/astellas-pharma-inc- discontinu.html (January 2012, date last accessed).
77. Heartwire press release. New factor Xa inhibitor betrixaban safe in phase 2 AF trial. 2010. http://www.theheart.org/article/1057065.do (January 2012, date last accessed).
78. Turpie AGG, Lip GYH, Minematsu K, Goto S, Renfurm RW, Wong KSL. Safety and tolerability of YM150 in subjects with non-valvular atrial fibrillation: A phase II study. (Abstract 1194). Eur Heart J 2010;31(Abstr. Supp.):173.
79. Lip GYH, Halperin JL, Petersen P, Rodgers GM, Renfurm RW. Safety and tolerability of the oral Factor Xa inhibitor, YM150 versus warfarin in 1297 patients with non-valvular atrial fibrillation: A dose confirmation study (OPAL-2). (Abstract O-TH-083). J Thromb Haemost 2011;9 Suppl 2:748.
80. Amadeus Investigators, Bousser MG, Bouthier J, Büller HR, Cohen AT, Crijns H et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: A randomised, open-label, non-inferiority trial. Lancet 2008;371:315-21.
81. Bloomberg News update. Sanofi-aventis stops development of two medicines (update 2). 2009. http://www.bloomberg.com/apps/news?pid=20601124&sid= aSQKk1p0REko (January 2012, date last accessed).
82. Mega JL. A new era for anticoagulation in atrial fibrillation. N Engl J Med 2011;365: 1052-4.