Novel Anticoagulants in Prevention of Cardioembolic Stroke in Patiens with Non-Valvular Atrial Fibrillation
Authors:
doc. MUDr. Jiří Bauer, CSc.
Authors‘ workplace:
1. LF UK a VFN v Praze
; Neurologická klinika
Published in:
Cesk Slov Neurol N 2013; 76/109(5): 550-558
Category:
Review Article
Overview
Anticoagulant therapy plays an important role in primary and secondary prevention of brain embolism in patients with non-valvular atrial fibrillation. Warfarin is the most commonly used anticoagulant in these indications. Warfarin significantly reduces the risk of stroke and death but increases the risk of bleeding. Life-threatening intracerebral haemorrhage is the most serious complication of anticoagulant therapy, with a mortality potentially exceeding 50%. Direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban) present promising alternatives to warfarin. This new anticoagulant therapy is as, or more, effective than warfarin and has demonstrated significantly better safety profile. In many patients, this therapy rightfully replaces warfarin.
Key words:
anticoagulant therapy – stroke – atrial fibrillation – warfarin – direct thrombin inhibitors – direct Xa factor inhibitors
The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Sources
1. Paciaroni M, Agnelli G, Micheli S, Caso V. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke. A meta‑analysis of randomized controlled trials. Stroke 2007; 38(2): 423– 430.
2. Lloyd‑ Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Ramachandran S et al. Lifetime risk for development of atrial fibrillation: The Framingham Heart Study. Circulation 2004; 110(9): 1042– 1046.
3. Kirchhof P, Lip GY, Van Gelder IC, Bax J, Hylek E, Kaab E et al. Comprehensive risk reduction in patients with atrial fibrillation: Emerging diagnostic and therapeutic options. Executive summary of the report from the 3rd AFNET/ EHRA concensus conference. Europace 2012; 14(1): 8– 27.
4. Camm AJ, Lip GYH, De Caterina R, Savelieva I,Atar D, Hohnloser SH et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an uptade of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhytm Association. Eur Heart J 2012; 33(21): 2719– 2747.
5. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A et al. Subclinical atrial fibrillation and the risk of stroke. E Engl J Med 2012; 366(2): 120– 129.
6. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D’Ágostino RB et al. A risk score for predicting stroke or death in individuals with new‑onset atrial fibrillation in the community. The Framingham Hearth Study. JAMA 2003; 290(8): 1049– 1056.
7. Čihák R, Heinc P, Haman L, Fiala M, Neužil P, To-man O. Fibrilace síní. Cor Vasa 2011; 53 (Suppl 1):27– 52.
8. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. ACC/ AHA/ ASC 2006 Guidelines for the Management of Patiens With Atrial Fibrillation: 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. Circulation 2006; 114(4): 257– 354.
9. 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). Eur Heart J 2010; 31(19): 2369– 2429.
10. Bauer J. Prevence kardioembolických cévních mozkových příhod. Interní Med 2012; 14(1): 26– 29.
11. Bauer J. Antikoagulační terapie v prevenci a léčbě ischemických iktů. Cesk Slov Neurol N 2010; 73/ 106(5): 480– 490.
12. 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– 867.
13. Hart RG, Palacio S, Pearce LA. Atrial fibrillation, stroke, and acute antithrombotic therapy: analysis of randomized clinical trials. Stroke 2002; 33(11): 2722– 2727.
14. Dalen JE. Prevention of embolic strokes: the role of the American College of Chest Physicians. Chest 2012; 141(2): 294– 299.
15. Gayatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence‑based clinical practice guedelines. Chest 2012; 141 (Suppl 2):7S– 47S.
16. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al. Evidence‑based management of anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians evidence‑based clinical practice guedelines. Chest 2012; 141 (Suppl 2): e152S– e184S.
17. You JJ, Singer DE, Howard PA, Lanc DA, Eckman MH, Fang MC et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence‑based clinical practice guedelines. Chest 2012; 141 (Suppl 2): e495S– e530S.
18. 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– 867.
19. Connolly SJ, Poque J, Eikelboom J, Flaker G, Commerford P, Franzosi MG et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depens on the quality of international normalized radio control achived by centers and countries as measured by time in therapeutic range. Circulation 2008; 118(20): 2029– 2037.
20. The European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25(5): 457– 507.
21. Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy. Stroke 2006; 37(1): 256– 262.
22. Aguilar MI, Hart RG, Kase CS, Freeman WD, Hoeben BJ, García RC et al. Treatment of warfarin‑associated intracerebral hemorrhage: literature review and expert opinion. Mayo Clin Proc 2007; 82(1): 82– 92.
23. Přibáň V, Holý M, Vonke I. Intrakraniální hematomy u warfarinizovaných pacientů – kazuistiky a doporučení léčby. Cesk Slov Neurol N 2009; 72/ 105(6): 570– 574.
24. Huhtakangas J, Tetri S, Juvela S, Soloheimo P, Bode MK, Hillbom M. Effect of increased warfarin use on warfarin‑related cerebral hemorrhage; a longitudinal population‑based study. Stroke 2011; 42(9): 2431– 2435.
25. Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy. Stroke 2006; 37(1): 256– 262.
26. Bauer J. Etiopatogeneze a současné možnosti terapie intracerebrálního krvácení. Cesk Slov Neurol N 2006; 69/ 102 (Suppl 2): 30– 33.
27. Gumulec J, Kessler P, Procházka V, Brejcha M, Penka M, Zänger M et al. Krvácivé komplikace a předávkování antikoagulační léčby. Vnitř Lék 2009; 55(3): 277– 289.
28. Bauer J. Léčba intracerebrálního krvácení – skepse nebo optimizmus? Neurol Prax 2006; 6: 328– 330.
29. Huttner HB, Schellinger PD, Hartmann M, Köhrmann M, Juettler E, Wikner J et al. Hematoma growth and outcome in treated neurocritical care patiens with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke 2006; 37(6): 1465– 1470.
30. Hart RG, Aguilar MI. Anticoagulation in atrial fibrillation: selected controversies including optima anticoagulation intensity, treatment of intracerebral hemorrhage. J Tromb Thrombolysis 2008; 25(1): 26– 32.
31. Fang MC, Go AS, Chang Y, Hylek EM, Henault LE, Jensvold NG et al. Death and disability from warfarin‑associated intracranial and extracranial hemorrhages. Am J Med 2007; 120(8): 700– 705.
32. Fang MC, Go AS, Hylek EM, Chan Y, Henault LE, Jensvold NG et al. Age and the risk of warfarin‑associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc 2006; 54(8): 1231– 1236.
33. Gallagher AM, Setakis E, Plumb JM, Clemens A, van Staa TP. Risk of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost 2011; 106(5): 968– 977.
34. Pecka M. Laboratorní monitorování antikoagulační léčby. Doporučení pro klinickou praxi (16. 3. 2006) [on-line]. Available from URL: http:/ / www.onkologickécentrum.cz/ downloads/ prirucky/ monitoring‑ antikoagulace‑ STH‑ III.06.pdf.
35. Kvasnička J, Hájková J, Bobčíková P, Kvasnička T, Dušková D, Poletínová Š et al. Prevalence polymorfismů CYP2C9 a VKORC1 v České republice a zamyšlení nad výhledy antikoagulační léčby warfarinem. Cor Vasa 2011; 53(10): 522– 526.
36. Remková A. Farmakogenetický algoritmus stanovenia dávky warfarínu. Interná Med 2008; 8(6): 3– 5.
37. Matýšková M, Penka M. Interakce antikoagulačních léků s potravinami a potravinovými doplňky. Intern Med Prax 2000; 5(2): 20– 23.
38. Olesen JB, Lip GY, Lane DA, Kober L, Hansen ML, Karasoy D et al. Vascular disease and stroke risk in atrial fibrillation: a Nationwide Cohort Study. Am J Med 2012; 125(8): 826.e13– 826.e23.
39. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. 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(2): 263– 272.
40. Olesen JB, Fauchier L, Lane DA, Taillandier S, Lip GY. Risk factor for stroke and thromboembolism in relation to age among patients with atrial fibrillation: the Loire Valley atrial fibrillation Project. Chest 2012; 141(1): 147– 153.
41. Kakar P, Lane D, Lip GY. Bleeding risk statification models in deciding on anticoagulation in patiens with atrial fibrillation: a useful complement to stroke risk stratification schema. Chest 2006; 130(5): 1296– 1299.
42. Ansell J. Warfarin versus new agents: interpreting the data. Hematology Am Soc Haematol Educ Program 2010; 2010: 221– 228.
43. Hylek EM. The need for new oral anticoagulants in clinical practice. J Cardiovasc Med 2009; 10(8): 605– 609.
44. Mega JL. A new era for anticoagulation in atrial fibrillation. N Engl J Med 2011; 365(11): 1052– 1054.
45. Eriksson BI, Quinlan DJ, Eikelboom JW. Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism. Annu Rev Med 2011; 62: 41– 57.
46. Zikria JC, Ansell J. Oral anticoagulation with factor Xa and thrombin inhibitors: on the threshold of change. Curr Opin Hematol 2009; 16(5): 347– 356.
47. Turpie AG. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008; 29(2): 155– 165.
48. Ogawa S, Koretsune Y, Yasaka M, Aizawa Y, Atarashi H, Inoue H et al. Antithrombotic therapy in atrial fibrillation. Evaluation and positioning of new oral anticoagulant agents. Circ J 2011; 75(7): 1539– 1547.
49. Nutescu EA, Shapiro NL, Chevalier A. New anticoagulant agents: direct thrombin inhibitors. Cardiol Clin 2008; 26(2): 169– 187.
50. 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(12): 1139– 1151.
51. Connolly SL, Ezekowitz MD, Yusuf S, Wallentin L.Newly identified events in the RE‑ LY trial. N Eng J Med 2010; 363(19): 1875– 1876.
52. Eisert WG, Hauel N, Stangier N, Wiener W, Clemens A, nav Ryn J. Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Tromb Vasc Biol 2010; 30(10): 1885– 1889.
53. Wallenin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG et al. Efficasy and safety of dabigatran compared with warfarin et different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an anylysis of the RE‑ LY trial. Lancet 2010; 376(9745): 975– 983.
54. Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD et al. Risk of 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– 667.
55. 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(3): 340– 347.
56. 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(10): 883– 891.
57. Granger CB, Alegander JH, Mc Murray JJ, Lopes RD, Hylek EM, Hanna M et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365(11): 981– 992.
58. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364(9): 806– 817.
59. Kansal AR, Sharma M, Bradley‑ Kennedy C, Clemens A, Monz U, Peng S et al. Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada. Comparative efficacy and cost‑effectiveness. Thromb Haemost 2012; 108(4): 672– 682.
60. Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly P at al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE‑ LY trial. Stroke 2012; 43(6): 1511– 1517.
61. Baglin T, Hillarp A, Tripodi A, Elalamy I, Buller H, Ageno W. Measuring Oral Direct Inhibitors (ODIs) of thrombin and factor Xa: a recommendation from the Subcommittee on Control of Anticoagulation of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2013; 11(4): 756–760.
62. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wiener W, Feuring M et al. Dabigatran etexilate – a novel reversible oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103(6): 116– 127.
63. Marlu R, Hodaj E, Paris A, Albaladejo P, Crackowski JL, Pernod G. Effect on non‑specific reversal agents on anticoagulant activity of dabigatran, rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost 2012; 108(2): 217– 224.
64. Shah SV, Gage BF. Cost‑effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011; 123(22): 2562– 2570.
65. Banerjee A, Lane DA, Torp‑ Pedersen C, Lip GY. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) vs no treatment in a “real world“ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107(3): 584– 589.
66. FDA Drug Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa. 2. 11. 2012 [on‑line]. Available from: htpp:/ / www.fda.gov/ Drugs/ Drugsafety/ ucm326580.htm.
67. Connolly SJ. Randomised comparison of the effecs of two doses of Dabigatran Etexilate of clinical outcomes over 4,3 years: Results of the RELY – ABLE trial. American Heart Association. Congress Report. Los Angeles, USA, 3– 7 November 2012, Session CS.04 [on‑line]. Available from: htpp:/ / www.spaf‑ academy.com/ speaker‑ toolbox/ congress‑ reports? dm.
68. Thelus R, Villines TC, Costner TS. Dabigatran versus warfarin among patients with atrial fibrillation: real‑ world postmarket results. American Heart Association. Congress Report. Los Angeles, USA, 3– 7 November 2012, Session APS.215.02 [on‑line]. Available from: htpp:/ / www.spaf‑ academy.com/ speaker‑ toolbox/ congress‑ reports? dm.
69. GLORIA‑ AF Registry Program (Phase I). Last updated October 17, 2012 [on‑line]. Available from: htpp:/ / www.clinicaltrials.gov/ show/ NCT01428765.
70. Apenteng PN, Murray ET, Holder R, Hobbs FD, Fitzmaurice DA. UK GARFIELD Investigators and GARFIELD Steering committee. An international longitunal registry of patients with atrial fibrillation at risk of stroke (GARFIELD): the UK protocol. BMC Cardiovasc Disord 2013; 13: 31.
71. Piccini JP, Fraulo ES, Ansell JE, Fonarow GC, Gersh BJ, Go AS et al. Outcomes registry for better informed treatment of atrial fibrillation: rationale and design of ORBIT-AF. Am Heart J 2011; 162(4): 606.e1–612.e1.
Labels
Paediatric neurology Neurosurgery NeurologyArticle was published in
Czech and Slovak Neurology and Neurosurgery
2013 Issue 5
Most read in this issue
- Wilson Disease
- Glioblastoma Multiforme – a Review of Pathogenesis, Biomarkers and Therapeutic Perspectives
- Tumefactive Variant of Multiple Sclerosis – Two Case Reports
- The 3F Test Dysarthric Profile – Normative Speach Values in Czech