Novel oral anticoagulants and stroke prevention in atrial fibrillation and chronic heart failure

Heart Failure Reviews

Volumn 19, Issue 3, 2014, Pages 391-401

  Boos, Christopher J ^a,b   Nam, Michael ^a   Camm, A J ^c  

^a POOLE HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

^b BOURNEMOUTH UNIVERSITY   (United Kingdom)

^c ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Apixaban; Atrial fibrillation; Dabigatran; Heart failure; Rivaroxaban; Stroke; Warfarin

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; APIXABAN; CLOPIDOGREL; D DIMER; DABIGATRAN ETEXILATE; PADGEM PROTEIN; PLACEBO; RIVAROXABAN; VON WILLEBRAND FACTOR; WARFARIN; BENZIMIDAZOLE DERIVATIVE; BETA ALANINE; DABIGATRAN; MORPHOLINE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRIDONE DERIVATIVE; THIOPHENE DERIVATIVE;

AGE DISTRIBUTION; ARTICLE; BRAIN BLOOD FLOW; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CHA2DS2 VASC SCORE; CHADS2 SCORE; DIAGNOSTIC ACCURACY; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CHOICE; DRUG CLEARANCE; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG INDICATION; DRUG MEGADOSE; DRUG POTENCY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; ENDOTHELIAL DYSFUNCTION; GASTROINTESTINAL HEMORRHAGE; HAS BLED SCORE; HEART ATRIUM CONTRACTION; HEART ATRIUM FIBRILLATION; HEART DEPOLARIZATION; HEART FAILURE; HEART INFARCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEART LEFT VENTRICLE FILLING; HEART OUTPUT; HEART PROTECTION; HUMAN; INTERMETHOD COMPARISON; KIDNEY CLEARANCE; LIVER CLEARANCE; MONOTHERAPY; MORTALITY; PREDICTION; PROPHYLAXIS; RISK ASSESSMENT; RISK FACTOR; RISK REDUCTION; SCORING SYSTEM; TACHYCARDIA; THROMBOCYTE ACTIVATION; THROMBOEMBOLISM; UNSPECIFIED SIDE EFFECT; ANALOGS AND DERIVATIVES; ATRIAL FIBRILLATION; CHEMICALLY INDUCED; CHRONIC DISEASE; COMPLICATION; DRUG MONITORING; HEMORRHAGE; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; SEVERITY OF ILLNESS INDEX; STROKE;

ANTICOAGULANTS; ATRIAL FIBRILLATION; BENZIMIDAZOLES; BETA-ALANINE; CHRONIC DISEASE; DRUG MONITORING; HEART FAILURE; HEMORRHAGE; HUMANS; MORPHOLINES; OUTCOME ASSESSMENT (HEALTH CARE); PYRAZOLES; PYRIDONES; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; STROKE; THIOPHENES; WARFARIN;

EID: 84898924472     PISSN: 13824147     EISSN: 15737322     Source Type: Journal    
DOI: 10.1007/s10741-013-9398-3     Document Type: Article

References (95)

1. Stewart S, Hart CL, Hole DJ, McMurray JJ (2001) Population prevalence, incidence, and predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 86(5):516-521
2. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ (2004) Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110(9):1042-1046
3. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS (2006) Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 14(2):119-125
4. Kazemian P, Oudit G, Jugdutt BI (2012) Atrial fibrillation and heart failure in the elderly. Heart Fail Rev 17(4-5):597-613
5. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P; ESC Committee for Practice Guidelines (CPG), Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S; Document Reviewers, Vardas P, Al-Attar N, Alfieri O, Angelini A, Blömstrom-Lundqvist C, Colonna P, De Sutter J, Ernst S, Goette A, Gorenek B, Hatala R, Heidbüchel H, Heldal M, Kristensen SD, Kolh P, Le Heuzey JY, Mavrakis H, Mont L, Filardi PP, Ponikowski P, Prendergast B, Rutten FH, Schotten U, Van Gelder IC, Verheugt FW. (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 33(21):2719-2747
6. Kannel WB, Wolf PA, Benjamin EJ, Levy D (1998) Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 82(8A):2N-9N
7. Lip GY, Boos CJ (2006) Antithrombotic treatment in atrial fibrillation. Heart 92(2):155-161
8. Lamassa M, Di Carlo A, Pracucci G, Basile AM, Trefoloni G, Vanni P, Spolveri S, Baruffi MC, Landini G, Ghetti A, Wolfe CD, Inzitari D (2001) Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project). Stroke 32(2):392-398
9. Thygesen SK, Frost L, Eagle KA, Johnsen SP (2009) Atrial fibrillation in patients with ischemic stroke: a population-based study. Clin Epidemiol 1:55-65
10. Balasubramaniam R, Kistler PM (2009) Atrial fibrillation in heart failure: the chicken or the egg? Heart 95(7):535-539
11. Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, D'Agostino RB, Murabito JM, Kannel WB, Benjamin EJ (2003) Temporal relation of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 107(23):2920-2925
12. Grönefeld GC, Hohnloser SH (2003) Heart failure complicated by atrial fibrillation: mechanistic, prognostic, and therapeutic implications. J Cardiovasc Pharmacol Ther 8(2):107-113
13. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna W, Seward JB, Iwasaka T, Tsang TS (2006) Incidence and mortality risk of congestive heart failure in atrial fibrillation patients: a community-based study over two decades. Eur Heart J 27(8):936-941
14. Piccini JP, Hernandez AF, Zhao X, Patel MR, Lewis WR, Peterson ED, Fonarow GC, The Guidelines Steering Committee and Hospitals (2009) Get with the guidelines steering committee and hospitals. Quality of care for atrial fibrillation among patients hospitalized for heart failure. J Am Coll Cardiol 54(14):1280-1289
15. Ingelgård A, Hollowell J, Reddy P, Gold K, Tran K, Fitzmaurice D (2006) What are the barriers to warfarin use in atrial fibrillation? Development of a questionnaire. J Thromb Thrombol 21(3):257-265
16. Fang MC, Go AS, Chang Y, Hylek EM, Henault LE, Jensvold NG, Singer DE (2007) Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 120(8):700-705
17. Boos CJ, Lip GY (2006) Ximelagatran: an eulogy. Thromb Res 118(3):301-304
18. Albers GW, Diener HC, Frison L, Grind M, Nevinson M, Partridge S, Halperin JL, Horrow J, Olsson SB, Petersen P, Vahanian A, SPORTIF Executive Steering Committee for the SPORTIF V Investigators (2005) Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 293(6):690-698
19. Investigators Amadeus, Bousser MG, Bouthier J, Büller HR, Cohen AT, Crijns H, Davidson BL, Halperin J, Hankey G, Levy S, Pengo V, Prandoni P, Prins MH, Tomkowski W, Torp-Pedersen C, Wyse DG (2008) Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 371(9609):315-321
20. Clark DM, Plumb VJ, Epstein AE, Kay GN (1997) Hemodynamic effects of an irregular sequence of ventricular cycle lengths during atrial fibrillation. J Am Coll Cardiol 30(4):1039-1045
21. Dries DL, Exner DV, Gersh BJ, Domanski MJ, Waclawiw MA, Stevenson LW (1998) Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of left ventricular dysfunction. J Am Coll Cardiol 32(3):695-703
22. Maisel WH, Stevenson LW (2003) Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol 91(6A):2D-8D
23. Middlekauff HR, Stevenson WG, Stevenson LW (1991) Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients. Circulation 84(1):40-48
24. Kindermann M, Reil JC, Pieske B, van Veldhuisen DJ, Böhm M (2008) Heart failure with normal left ventricular ejection fraction: what is the evidence? Trends Cardiovasc Med 18(8):280-292
25. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355(3):251-259
26. Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, Tu JV, Levy D (2009) Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the Framingham heart study of the national heart, lung, and blood institute. Circulation 119(24):3070-3077
27. Gheorghiade M, Vaduganathan M, Fonarow GC, Greene SJ, Greenberg BH, Liu PP, Massie BM, Mehra MR, Metra M, Zannad F, Cleland JG, van Veldhuisen DJ, Shah AN, Butler J (2012) Anticoagulation in heart failure: current status and future direction. Heart Fail Rev. doi: 10.1007/s10741-012-9343-x
28. Lip GY, Gibbs CR (1999) Does heart failure confer a hypercoagulable state? Vichow's triad revisited. J Am Coll Cardiol 33(5):1424-1426
29. Watson T, Shantsila E, Lip GY (2009) Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet 373(9658):155-166
30. Jafri SM, Mammen EF, Masura J, Goldstein S (1997) Effects of warfarin on markers of hypercoagulability in patients with heart failure. Am Heart J 134(1):27-36
31. Gibbs CR, Blann AD, Watson RD, Lip GY (2001) Abnormalities of haemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm: effects of angiotensin-converting enzyme inhibitor and beta-blocker therapy. Circulation 103(13):1746-1751
32. Jafri SM, Ozawa T, Mammen E, Levine TB, Johnson C, Goldstein S (1993) Platelet function, thrombin and fibrinolytic activity in patients with heart failure. Eur Heart J 14(2):205-212
33. Nakamura M, Sugawara S, Arakawa N, Nagano M, Shizuka T, Shimoda Y, Sakai T, Hiramori K (2004) Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure. J Card Fail 10(1):36-42
34. Witt BJ, Gami AS, Ballman KV, Brown RD Jr, Meverden RA, Jacobsen SJ, Roger VL (2007) The incidence of ischemic stroke in chronic heart failure: a meta-analysis. J Card Fail 13(6):489-496
35. Lip GY, Pearce LA, Chin BS, Conway DS, Hart RG (2005) Effects of congestive heart failure on plasma von Willebrand factor and soluble P-selectin concentrations in patients with non-valvar atrial fibrillation. Heart 91(6):759-763
36. Pai RG, Varadarajan P (2007) Prognostic significance of atrial fibrillation is a function of left ventricular ejection fraction. Clin Cardiol 30(7):349-354
37. Olsson LG, Swedberg K, Ducharme A, Granger CB, Michelson EL, McMurray JJ, Puu M, Yusuf S, Pfeffer MA, CHARM Investigators (2006) Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) program. J Am Coll Cardiol 47(10):1997-2004
38. Loh E, Sutton MS, Wun CC, Rouleu JL, Flaker GC, Gottlieb SS, Lamas GA, Moye LA, Goldhaber SZ, Pfeffer MA (1997) Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 336(4):251-257
39. AF-Investigators (1998) Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Arch Intern Med 158(12):1316-1320
40. Banerjee A, Taillandier S, Olesen JB, Lane DA, Lallemand B, Lip GY, Fauchier L (2012) Ejection fraction and outcomes in patients with atrial fibrillation and heart failure: the Loire Valley Atrial Fibrillation Project. Eur J Heart Fail 14(3):295-301
41. Jang SJ, Kim MS, Park HJ, Han S, Kang DH, Song JK, Park SW, Park SJ, Kim JJ (2013) Impact of heart failure with normal ejection fraction on the occurrence of ischaemic stroke in patients with atrial fibrillation. Heart 99(1):17-21
42. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Guidelines (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33(14):1787-1847
43. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ (2001) Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 285(2):2864-2870
44. Hughes M, Lip GY (2008) Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thomb Haemost 99(2):295-304
45. Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J, Selmer C, Ahlehoff O, Olsen AM, Gislason GH, Torp-Pedersen C (2011) Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. Br Med J 342:d124
46. Friberg L, Benson L, Rosenqvist M, Lip GY (2012) Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study. BMJ 344:e3522
47. Avgil Tsadok M, Jackevicius CA, Rahme E, Humphries KH, Behlouli H, Pilote L (2012) Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation. JAMA 307(18):1952-1958
48. Olesen JB, Fauchier L, Lane DA, Taillandier S, Lip GY (2012) Risk factors for stroke and thromboembolism in relation to age among patients with atrial fibrillation: the Loire Valley Atrial Fibrillation Project. Chest 141(1):147-153
49. Olesen JB, Lip GY, Lane DA, Køber L, Hansen ML, Karasoy D, Hansen CM, Gislason GH, Torp-Pedersen C (2012) Vascular disease and stroke risk in atrial fibrillation: a nationwide cohort study. Am J Med 125(8):826.e13-826.e23
50. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ (2010) 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 137(2):263-272
51. Lane DA, Lip GYH (2012) Use of the CHA2DS2-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in non-valvular atrial fibrillation. Circulation 126(7):860-865
52. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY (2010) 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 138(5):1093-1100
53. Hart RG, Benavente O, McBride R, Pearce LA (1999) Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 131(7):492-501
54. Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146(12):857-867
55. SPAF Investigators (1991) Stroke prevention in atrial fibrillation study. Final results. Circulation 84(2):527-539
56. Mega JL (2011) A new era for anticoagulation in atrial fibrillation. N Engl J Med 365(11):1052-1054
57. Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, Murray E, BAFTA investigators, Midland Research Practices Network (MidReC) (2007) 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 370(9586):493-503
58. Rash A, Downes T, Portner R, Yeo WW, Morgan N, Channer KS (2007) A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 36(2):151-156
59. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2011) Heart disease and stroke statistics - 2011 update: a report from the American Heart Association. Circulation 123(4):e18-e209
60. Olesen JB, Lip GY, Lindhardsen J, Lane DA, Ahlehoff O, Hansen ML, Raunsø J, Tolstrup JS, Hansen PR, Gislason GH, Torp-Pedersen C (2011) 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 106(4):739-749
61. Schumann SA, Ewigman B (2007) Stroke prevention: age alone does not rule out warfarin. J Fam Pract 56(11):902-906
62. Singer DE, Chang Y, Fang MC, Borowsky LH, Pomernacki NK, Udaltsova N, Go AS (2009) The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 151(5):297-305
63. Azoulay L, Dell'Aniello S, Simon TA, Langleben D, Renoux C, Suissa S (2012) A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case-control study. BMC Cardiovasc Disord 12:49
64. Friberg L, Rosenqvist M, Lip GY (2012) Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 125(19):2298-2307
65. Lip GY (2011) The role of aspirin for stroke prevention in atrial fibrillation. Nat Rev Cardiol 8(10):602-606
66. Ogilvie IM, Welner SA, Cowell W, Lip GY (2011) Ischaemic stroke and bleeding rates in 'real world' atrial fibrillation patients. Thromb Haemost 106(1):34-44
67. Mahmud A, Bennett K, Okechukwu I, Feely J (2007) National underuse of anti-thrombotic therapy in chronic atrial fibrillation identified from digoxin prescribing. Br J Clin Pharmacol 64(5):706-709
68. Kowey PR, Reiffel JA, Myerburg R, Naccarelli GV, Packer DL, Pratt CM, Reiter MJ, Waldo AL (2010) AFFECTS Scientific Advisory Committee and Investigators. Warfarin and aspirin use in atrial fibrillation among practicing cardiologists (from the AFFECTS Registry). Am J Cardiol 105(8):1130-1134
69. ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, Pfeffer M, Hohnloser S, Yusuf S (2006) 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 367(9526):1903-1912
70. ACTIVE Investigators, Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S (2009) Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 360(20):2066-2078
71. Tzeis S, Andrikopoulos G (2012) Novel anticoagulants for atrial fibrillation: a critical appraisal. Angiology 63(3):164-170
72. Cabral KP, Ansell J, Hylek EM (2011) Future directions of stroke prevention in atrial fibrillation: the potential impact of novel anticoagulants and stroke risk stratification. J Thromb Haemost 9(3):441-449
73. Stangier J, Stähle H, Rathgen K, Fuhr R (2008) Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 47(1):47-59
74. Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, van Ryn J (2010) Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol 30(10):1885-1889
75. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY Steering Committee and Investigators (2009) Dabigatran versus Warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139-1151
76. Ezekowitz MD, Connolly S, Parekh A, Reilly PA, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S (2009) Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J 157(5):805-810
77. Bytzer P, Connolly SJ, Yang S, Ezekowitz M, Formella S, Reilly PA, Aisenberg J (2013) Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial. Clin Gastroenterol Hepatol 11(3):246-252
78. Perzborn E, Roehrig S, Straub A, Kubitza D, Mueck W, Laux V (2010) Rivaroxaban: a new oral factor Xa inhibitor. Arterioscler Thromb Biol 30(3):376-381
79. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, ROCKETAF Investigators (2011) Rivaroxaban versus Warfarin in non valvular atrial fibrillation. N Engl J Med 365(10):883-891
80. Rocket, AF Study Investigators (2010) 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 159(3):340-347
81. Frost C, Wang J, Nepal S, Schuster A, Barrett YC, Mosqueda-Garcia R, Reeves RA, Lacreta F (2013) Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol 75(2):476-487
82. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, ARISTOTLE Committees Investigators, (2011) Apixaban versus Warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981-992
83. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O'Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S, AVERROES Steering Committee Investigators (2011) Apixaban in patients with atrial fibrillation. N Engl J Med 364(9):806-817
84. Eikelboom JW, O'Donnell M, Yusuf S, Diaz R, Flaker G, Hart R, Hohnloser S, Joyner C, Lawrence J, Pais P, Pogue J, Synhorst D, Connolly SJ (2010) 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 159(3):348-353
85. Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD, Gersh BJ, Granger CB, Hanna M, Horowitz J, Hylek EM, McMurray JJ, Verheugt FW, Wallentin L, ARISTOTLE Investigators (2010) Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J 159(3):331-339
86. McMurray JJ, Ezekowitz JA, Lewis BS, Gersh BJ, van Diepen S, Amerena J, Bartunek J, Commerford P, Oh BH, Harjola VP, Al-Khatib SM, Hanna M, Alexander JH, Lopes RD, Wojdyla DM, Wallentin L, Granger CB (2013) Left ventricular systolic dysfunction, heart failure and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail 6(3):451-460
87. Lip GY, Larsen TB, Skjøth F, Rasmussen LH (2012) Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation. J Am Coll Cardiol 60(8):738-746
88. Gheorghiade M, Thyssen A, Zolynas R, Nadar VK, Greenberg BH, Mehra M, Sun X, Tian H, Plotnikov AN, Burton P (2011) Pharmacokinetics and pharmacodynamics of rivaroxaban and its effect on biomarkers of hypercoagulability in patients with chronic heart failure. J Heart Lung Transplant 30(2):218-226
89. Deitelzweig S, Amin A, Jing Y, Makenbaeva D, Wiederkehr D, Lin J, Graham J (2012) Medical cost reductions associated with the usage of novel oral anticoagulants vs warfarin among atrial fibrillation patients, based on the RE-LY, ROCKET-AF, and ARISTOTLE trials. J Med Econ 15(4):776-785
90. Pink J, Lane S, Pirmohamed M, Hughes D (2011) Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ 343:1-14
91. Deen R (2011) Use of direct observed therapy to confirm compliance in a warfarin clinic. J Patient Saf 7(4):232-233
92. Burkiewicz JS (2005) Effect of access to anticoagulation management services on warfarin use in patients with atrial fibrillation. Pharmacotherapy 25(8):1062-1067
93. Davis NJ, Billett HH, Cohen HW, Arnsten JH (2005) Impact of adherence, knowledge, and quality of life on anticoagulation control. Ann Pharmacother 39(4):632-636
94. Van de Werf F, Brueckmann M, Connolly SJ, Friedman J, Granger CB, Härtter S, Harper R, Kappetein AP, Lehr T, Mack MJ, Noack H, Eikelboom JW (2012) 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 163(6):931-937
95. Nagarakanti R, Ezekowitz MD, Oldgren J, Yang S, Chernick M, Aikens TH, Flaker G, Brugada J, Kamensky G, Parekh A, Reilly PA, Yusuf S, Connolly SJ (2011) Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 123(2):131-136