Oral IIa and Xa inhibitors for prevention of stroke in atrial fibrillation: Clinical studies and regulatory considerations

Current Clinical Pharmacology

Volumn 7, Issue 3, 2012, Pages 166-174

  Deftereos, Spyridon ^a   Tsounis, Dimitrios ^a   Giannopoulos, Georgios ^a   Kossyvakis, Charalampos ^a   Panagopoulou, Vasiliki ^a   Raisakis, Konstantinos ^a   Stefanadis, Christodoulos ^b  

^a G GENNIMATAS GENERAL HOSPITAL   (Greece)

^b UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

Atrial fibrillation; Direct thrombin inhibitors; Factor Xa inhibitors; Oral anticoagulants; Stroke prevention

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTIVITAMIN K; APIXABAN; ATECEGATRAN METOXIL; BETRIXABAN; BLOOD CLOTTING FACTOR 10A INHIBITOR; CLOPIDOGREL; DABIGATRAN; DABIGATRAN ETEXILATE; DAREXABAN; EDOXABAN; ENOXAPARIN; LETAXABAN; N [2 [4 (1 METHYL 4 PIPERIDINYL) 1 PIPERAZINYL] 2 OXO 1 PHENYLETHYL] 1H INDOLE 6 CARBOXAMIDE; RIVAROXABAN; THROMBIN INHIBITOR; WARFARIN; XIMELAGATRAN;

ANTICOAGULANT THERAPY; ARTICLE; BLEEDING; BRAIN HEMORRHAGE; CLINICAL PRACTICE; CLINICAL STUDY; DRUG APPROVAL; DRUG EFFICACY; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; DYSPEPSIA; GASTROINTESTINAL HEMORRHAGE; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); POSTMARKETING SURVEILLANCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; STROKE; THROMBOEMBOLISM; THROMBOSIS; VENOUS THROMBOEMBOLISM;

ADMINISTRATION, ORAL; ANIMALS; ANTICOAGULANTS; ATRIAL FIBRILLATION; FACTOR XA; HUMANS; PROTHROMBIN; RANDOMIZED CONTROLLED TRIALS AS TOPIC; STROKE;

EID: 84862609794     PISSN: 15748847     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488412800958749     Document Type: Article

References (70)

1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics - 2011 update. Circulation 2011; 123(4): e18-e209.
2. Go AS, Hylek EM, Phillips KA, 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(18): 2370-2375.
3. Heeringa J, van der Kuip DAM, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: The Rotterdam study. Eur Heart J 2006; 27(8): 949.
4. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted county, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006; 114(2): 119-125.
5. Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in atrial fibrillation: Recommendations from a consensus conference organized by the german atrial fibrillation competence network and the european heart rhythm association. Europace 2007; 9(11): 1006-1023.
6. Gorin L, Fauchier L, Nonin E, et al. Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1. Thromb Haemost 2010; 103(4): 833-840.
7. Menke J, Lüthje L, Kastrup A, et al. Thromboembolism in atrial fibrillation. Am J Cardiol 2010; 105(4): 502-510.
8. Naccarelli GV, Johnston SS, Dalal M, et al. Rates and implications for hospitalization of patients ≥65 years of age with atrial fibrillation/flutter. Am J Cardiol 2011; 109(4): 543-549.
9. Peinado R, Arribas F, Ormaetxe JM, et al. Variation in quality of life with type of atrial fibrillation. Rev Esp Cardiol 2010; 63(12): 1402-1409.
10. Schirmer SH, Baumhäkel M, Neuberger HR, et al. Novel anticoagulants for stroke prevention in atrial fibrillation: Current clinical evidence and future developments. J Am Coll Cardiol 2010; 56(25): 2067-2076.
11. Hart RG, Oczkowski WJ. What's new in stroke? The top 10 studies of 2009-2011: Part II. Pol Arch Med Wewn 2011; 121(6): 200-207.
12. Röther J, Crijns H. Prevention of stroke in patients with atrial fibrillation: The role of new antiarrhythmic and antithrombotic drugs. Cerebrovasc Dis 2010; 30(3): 314-322.
13. Brüggenjürgen B, Rossnagel K, Roll S, et al. The impact of atrial fibrillation on the cost of stroke: The berlin acute stroke study. Value Health 2007; 10(2): 137-143.
14. Camm AJ, Kirchhof P, Lip GY, 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(10): 1360-1420.
15. 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(12): 857-67.
16. Mant J, Hobbs FD, Fletcher K, 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(9586): 493-503.
17. Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W): A randomised controlled trial. Lancet 2006; 367(9526): 1903-1912.
18. Baker WL, Cios DA, Sander SD, et al. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the united states. J Manag Care Pharm 2009; 15(3): 244-252.
19. Nieuwlaat R, Capucci A, Camm AJ, et al. Atrial fibrillation management: A prospective survey in ESC member countries: The euro heart survey on atrial fibrillation. Eur Heart J 2005; 26(22): 2422-2434.
20. Aithal GP, Day CP, Kesteven PJ, et al. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353(9154): 717-719.
21. De Caterina R, Hylek EM. Stroke prevention in atrial fibrillation: Current status and near-future directions. Am J Med 2011; 124(9): 793-799.
22. Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives. Thromb Res 2007; 120(1): 1-10.
23. Laux V, Perzborn E, Heitmeier S, et al. Direct inhibitors of coagulation proteins - the end of the heparin and low-molecularweight heparin era for anticoagulant therapy? Thromb Haemost 2009; 102(5): 892-899.
24. Sattari M, Lowenthal DT. Novel oral anticoagulants in development: Dabigatran, rivaroxaban, and apixaban. Am J Ther 2011; 18(4): 332-338.
25. Boudes PF. The challenges of new drugs benefits and risks analysis: Lessons from the ximelagatran FDA cardiovascular advisory committee. Contemp Clin Trials 2006; 27(5): 432-440.
26. Halperin JL, Executive Steering Committee, SPORTIF III and V Study Investigators. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J 2003; 146(3): 431-438.
27. Ezekowitz MD, Connolly S, Parekh A, et al. Rationale and design of RE-LY: Randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J 2009; 157(5): 805-10, 810.e1-2.
28. Ma TK, Yan BP, Lam YY. Dabigatran etexilate versus warfarin as the oral anticoagulant of choice? A review of clinical data. Pharmacol Ther 2011; 129(2): 185-194.
29. Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: An update. J Thromb Thrombolysis 2011; 31(3): 326-343.
30. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361(12): 1139-1151.
31. Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: An analysis of the RE-LY trial. Lancet 2010; 376(9745): 975-983.
32. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identified events in the RE-LY trial. N Engl J Med 2010; 363(19): 1875-1876.
33. Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (randomized evaluation of long-term anticoagulation therapy) trial. Circulation 2012; 125(5): 669-676.
34. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: Meta-analysis of noninferiority randomized controlled trials. Arch Intern Med 2012; 172(5): 397-402.
35. Oldgren J, Alings M, Darius H, et al. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: A subgroup analysis of the RE-LY trial. Ann Intern Med 2011; 155(10): 660-7, W204.
36. RELY-ABLE long term multi-center extension of dabigatran treatment in patients with atrial fibrillation who completed RE-LY trial. [ClinicalTrials.gov]. [updated 2012, Feb 8; cited 2012, Feb 25]. Available from: http://clinicaltrials.gov/ct2/show/NCT00808067?term=rely+able&rank=1
37. Steffel J, Braunwald E. Novel oral anticoagulants: Focus on stroke prevention and treatment of venous thrombo-embolism. Eur Heart J 2011; 32(16): 1968-1976, 1976a.
38. Olsson SB, Rasmussen LH, Tveit A, et al. Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Thromb Haemost 2010; 103(3): 604-612.
39. Lip GY, Rasmussen LH, Olsson SB, et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: A phase II study of AZD0837 in patients who are appropriate for but unable or unwilling to take vitamin K antagonist therapy. Thromb Res 2011; 127(2): 91-99.
40. Johansson S, Cullberg M, Eriksson UG, et al. Single-dose pharmacokinetics, pharmacodynamics and safety of AZD0837, a novel oral direct thrombin inhibitor, in young healthy male subjects. Int J Clin Pharmacol Ther 2011; 49(4): 258-267.
41. Lip GY, Rasmussen LH, Olsson SB, et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: A randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. Vitamin K antagonists. Eur Heart J 2009; 30(23): 2897-2907.
42. Jiang J, Hu Y, Zhang J, et al. Safety, pharmacokinetics and pharmacodynamics of single doses of rivaroxaban - an oral, direct factor xa inhibitor - in elderly chinese subjects. Thromb Haemost 2010; 103(1): 234-241.
43. Chen T, Lam S. Rivaroxaban: An oral direct factor xa inhibitor for the prevention of thromboembolism. Cardiol Rev 2009; 17(4): 192-7.
44. Turpie AG. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008; 29(2): 155-165.
45. de Candia M, Lopopolo G, Altomare C. Novel factor xa inhibitors: A patent review. Expert Opin Ther Pat 2009; 19(11): 1535-1580.
46. Samama CM. New anticoagulants: Pharmacology and clinical studies. Wien Med Wochenschr 2011; 161(3-4): 54-7.
47. Kubitza D, Becka M, Voith B, et al. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor xa inhibitor. Clin Pharmacol Ther 2005; 78(4): 412-421.
48. Kubitza D, Becka M, Wensing G, et al. 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(12): 873-880.
49. Eriksson BI, Borris LC, Dahl OE, et al. A once-daily, oral, direct factor xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation 2006; 114(22): 2374-2381.
50. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365(10): 883-891.
51. Fox KA, Piccini JP, Wojdyla D, 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(19): 2387-2394.
52. Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009; 37(1): 74-81.
53. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364(9): 806-817.
54. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365(11): 981-992.
55. Wallentin L, Collet J. ARISTOTLE: Efficacy and safety of apixaban compared to warfarin at different levels of INR control for stroke prevention in 18,202 patients with atrial fibrillation in the ARISTOTLE trial.[ESC Congress Reports]. [updated 2011, Aug 28; cited 2012, Feb 19]. Available from: http://www.escardio.org/congresses/esc-2011/congress-reports/Pages/709-3-ARISTOTLE.aspx
56. Ogata K, Mendell-Harary J, Tachibana M, et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol 2010; 50(7): 743-753.
57. Mendell J, Tachibana M, Shi M, et al. Effects of food on the pharmacokinetics of edoxaban, an oral direct factor xa inhibitor, in healthy volunteers. J Clin Pharmacol 2011; 51(5): 687-694.
58. Camm AJ, Bounameaux H. Edoxaban: A new oral direct factor xa inhibitor. Drugs 2011; 71(12): 1503-1526.
59. Ruff CT, Giugliano RP, Antman EM, 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 fibrillationthrombolysis in myocardial infarction study 48 (ENGAGE AFTIMI 48). Am Heart J 2010; 160(4): 635-641.
60. Agnelli G, Haas S, Ginsberg JS, et al. A phase II study of the oral factor xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement. J Thromb Haemost 2007; 5(4): 746-753.
61. Turpie AG, Bauer KA, Davidson BL, et al. A randomized evaluation of betrixaban, an oral factor xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost 2009; 101(1): 68-76.
62. Eriksson BI, Turpie AG, Lassen MR, et al. Prevention of venous thromboembolism with an oral factor xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2). J Thromb Haemost 2010; 8(4): 714-721.
63. Weitz JI, Cao C, Eriksson BI, et al. A dose-finding study with TAK-442, an oral factor xa inhibitor, in patients undergoing elective total knee replacement surgery. Thromb Haemost 2010; 104(6): 1150-1157.
64. EXPLORE-Xa study, 2010 [NCT00742859] preliminary results. [TrialResults-center C2004-2012]. [updated 2010; cited 2012, Feb 20]. Available from: http://www.trialresultscenter.org/study10407-EXPLORE-Xa.htm
65. Piccini JP, Lopes RD, Mahaffey KW. Oral factor xa inhibitors for the prevention of stroke in atrial fibrillation. Curr Opin Cardiol 2010; 25(4): 312-320.
66. Lip, Halperin, Petersen, et al. Safety and tolerability of the oral factor xa inhibitor, YM150 vs. Warfarin in 1297 patients with nonvalvular atrial fibrillation: A dose confirmation study (OPAL-2). J Thromb Haemost 2011(9 Suppl 2): 748.
67. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365(24): 2333-2335.
68. Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrateclinical perspective. Circulation 2011; 124(14): 1573-1579.
69. Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012; 366(9): 864-866.
70. Freeman JV, Zhu RP, Owens DK, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 2011; 154(1): 1-11.