Anticoagulant Therapy in the Prevention and Treatment of Ischemic Stroke


Authors: J. Bauer
Authors‘ workplace: Neurologická klinika, 1. LF UK a VFN v Praze
Published in: Cesk Slov Neurol N 2010; 73/106(5): 480-491
Category: Minimonography

Overview

Anticoagulant therapy plays an important role in thromboembolic disorders, in primary and secondary prevention as well as treatment, and especially in the prevention of brain systemic embolism in patients with non-valvular atrial fibrillation and other sources of cardioembolic strokes. Unless contraindicated, warfarin is recommended for the treatment of these patients. Warfarin significantly reduces the risks of stroke and death, but increases that of haemorrhage. Life-threatening intracerebral haemorrhage is the most serious complication of oral anticoagulant therapy, with a mortality that can exceed 50%. The need for frequent laboratory monitoring, a narrow therapeutic window, and a plethora of interactions with food and drugs are also reasons to seek new, safe, effective anticoagulant agents that are convenient to use. New oral direct thrombin inhibitors and factor Xa inhibitors present promising alternatives to warfarin. Unfractionated heparin or low-molecular-weight heparins are not recommended for the prevention of early stroke recurrence in patients with acute ischemic stroke of cardioembolic origin. Low-dose unfractionated subcutaneous heparin or low-molecular-weight heparins should be considered for patients with acute ischemic stroke at high risk of deep venous thrombosis or pulmonary embolism.

Key words:
anticoagulant therapy – stroke – warfarin – heparin – low-molecular-weight heparins – direct thrombin inhibitors – direct Xa factor inhibitors


Sources

1. Hrachovinová I. Hemokoagulace. In: Vojáček J, Malý M et al (eds). Arteriální a žilní trombóza v klinické praxi. Praha: Grada Publishing 2004: 45–50.

2. 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.

3. Pecka M. Laboratorní monitorování antikoagulační léčby. Doporučení pro klinickou praxi. [online]. Dostupné z URL: http://www.onkologickécentrum.cz/downloads/prirucky/monitoring-antikoagulace-STH-III.06.pdf.

4. Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003; 107(12): 1692–1711.

5. Bousser MG, Bouthier J, Büller HR, Cohen AT, Crijns H, Davidson BL et al. Comparison of indaparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008; 371(9609): 315–321.

6. European Stroke Organisation (ESO) Executive Committee, ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25(5): 457–507.

7. Hirsh J, Guyatt G, Albert GW, Harrington R, ­Schünemann HJ. Antithrombotic and thrombolytic therapy: American College of Chest Physicians ­Evidence-Based Clinical Practice Guidelines (8th Ed.). Chest 2008; 133 (Suppl 6): 110S–112S.

8. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D´Agostino 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.

9. 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.

10. Singer DE, Albert GW, Dalen JE, Fang MC, Go AS, Halperin JL et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.). Chest 2008; 133 (Suppl 6): 546S–592S.

11. Reková-Vymětalová P, Bauer J, Goláň L, Fiksa J, Sváčková D, Lakomý C et al. Abnormality srdečního síňového septa a cévní mozkové příhody. Cesk Slov Neurol N 2006; 69/102(1): 27–32.

12. Kvasnička J. Trombofilie a trombotické stavy v klinické praxi. Praha: Grada Publishing 2003.

13. Bulíková A, Smejkal P, Zavřelová J, Chlupová G, Penka M. Získané inhibitory krevního srážení. Intern Med 2008; 10(7 a 8): 336–339.

14. 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.

15. Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy. Stroke 2006; 37(1): 256–262.

16. Huttner HB, Schellinger PD, Hartmann M, ­Köhrmann M, Juettler E, Wikner J et al. Hematoma growth and outcome in treated neurocritical care patients 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.

17. Bauer J. Léčba intracerebrálního krvácení – skepse nebo optimizmus? Neurol prax 2006; 6: 328–330.

18. 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.

19. Gross PL, Weitz JI. New anticoagulants for treatment of venous thromboembolism. Arterioscler Tromb Vasc Biol 2008; 28(3): 380–386.

20. Remková A. Farmakogenetický algoritmus stanovenia dávky warfarínu. Interná medicina 2008; 8(6): 3–5.

21. Kakar P, Lane D, Lip GY. Bleeding risk statification models in deciding on anticoagulation in patients with atrial fibrillation. Chest 2006; 130(5): 1296–1299.

22. Hankey GJ. Stroke: Your questions answered. Edinburgh: Churchill Livingstone 2002.

23. Deerhake JP, Merz JC, Cooper JV, Eagle KA, Fay WP. The duration of anticoagulation bridging therapy in clinical practice may significantly exceed that observe in clinical trials. J Thromb Thrombolysis 2007; 23(2): 107–113.

24. Matýšková M, Penka M. Interakce antikoagulačních léků s potravinami a potravinovými doplňky. Int Med 2000; 5(2): 20–23.

25. Cerebrovaskulární sekce České neurologické společnosti ČLS JEP. Protokol trombolytické terapie [online]. Dostupné z URL: http://www.cmp.cz/public/d4/9d/b3/3999_16382_protokol_trombolyticke_terapie.pdf

26. Morgenstern LB, Hemphill JC jr, Anderson C, ­Becker K, Broderick JP, Connolly ES et al. Guidelines for the management of spontaneous intracerebral hemorrhage. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41(9): 2108–2129.

27. Sørensen B, Johansen P, Nielsen GL, Sorensen JC, Ingerslev J. Reversal of the International Normalized Ratio with recombinant activated factor VII in central nervous system bleeding during warfarin thromboprophylaxis: clinical and biochemical aspects. Blood Coagul Fibrinolysis 2003; 14(5): 469–477.

28. 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.

29. Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM. Urgent reversal of warfarin with protrombin complex concentrate. J Tromb Haemost 2006; 4(5): 967–970.

30. Steiner T, Rosand J, Diringer M. Intracerebral hemorrhage associated with oral anticoagulant therapy. Stroke 2006; 37(1): 256–262.

31. Bauer J. Etiopatogeneze a současné možnosti terapie intracerebrálního krvácení. Cesk Slov Neurol N 2006; 69/102 (Suppl 2): 30–33.

32. Goldstein JN, Thomas SH, Frontiero V, Joseph A, Engel Ch, Snider R et al. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke 2006; 37(1): 151–155.

33. 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.

34. Wani M, Nga E, Navaratnasingham R. Should a patient with primary intracerebral haemorrhage receive antiplatelet or anticoagulant therapy? BMJ 2005; 331(7514): 439–442.

35. Brejcha M, Gumulec J, Penka M, Klodová D, ­Wróbel M, Bogoczová E. Příprava pacientů s antikoagulační léčbou k invazivním zákrokům. Vnitř Lék 2009; 55(3): 272–275.

36. ACC/AHA/ASC 2006 Guidelines for the Management of Patients With Atrial Fibrillation. Circulation 2006; 114(4): 257–354.

37. Sellman JS, Holman RL. Thromboembolism during pregnancy. Medicína po promoci 2002; 3(1): 54–61.

38. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108(3): 776–789.

39. Hart RG, Palacio S, Pearce LA. Atrial fibrillation, stroke, and acute antithrombotic therapy: analysis of randomized clinical trials. Stroke 2002; 33(11): ­2722–2727.

40. Coull BM, Williams LS, Golstein LB, Meschia JF, ­Heitzman D, Chaturvedi S et al. Anticoagulants and antiplatelet agents in acute stroke. Report of the Point Stroke Guideline Development Committee of American Stroke Association. Neurology 2002; 59(1): 13–22.

41. Sandercock P, Counsell C, Kamal AK. Anticoagulants for Acute Ischemic Stroke. Stroke 2009; 40(7): 483–484.

42. 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.

43. Warlow CP, Dennis MS, van Gijn J, Hankey GJ, Sandercoock PA, Bamford JM et al. Stroke: a practical guide to management. 2nd. ed. Oxford: Blackwell Science 2001.

44. Kalita Z et al. Akutní cévní mozkové příhody. Praha: Jessenius Maxdorf 2006.

45. Chamorro A, Busse O, Obach V, Toni D, ­Sandercock P, Reverter JC et al. The rapid anticoagulation prevents ischaemic damage study in acute stroke – final results from the writing committee. Cerebrovasc Dis 2005; 19(6): 402–404.

46. Geerts WH, Bergqvist D, Pineo GF, Heit JA, ­Samana CM, Larsen MR et al. Prevention of venous thromboembolis: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.). Chest 2008; 133 (Suppl 6): 381S–453S.

47. Kearon C, Kahn SR Angelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Praktice Guidelines (8th Ed.). Chest 2008; 133 (Suppl 6): 454S–545S.

48. Gumulec J, Penka M, Bezděk R, Wróbel M, ­Kessler P, Brejcha M et al. Prevence žilní tromboembolické nemoci: obecně platná pravidla. [online]. Dostupné z URL: http://www.onkologickecentrum.cz/downloads/prirucky/prevence-TEN-STH-V06.pdf.

49. Bergmann JF, Cohen AT, Tapson VF, ­Golhhaber SZ, Kakkar AK, Deslandes B. Venous tromboembolism risk and prophylaxis in hospitalised medically ill ­patients. The ENDORSE Global Survey. J Tromb ­Haemost 2010; 103(4): 726–748.

50. Poul H, Kessler P. Trombofilní stavy: Význam pro prevenci a léčbu žilního tromboembolizmu. Vnitř Lék 2009; 55(3): 242–252.

51. Čížek V, Kučera D, Válka M, Bartoš P, Maděrič D, Pleva M. Úloha kaválních filtrů v prevenci plicní embolie. Vnitř Lék 2009; 55(3): 267–271.

52. Kalina M et al. Cévní mozková příhoda v medicínské praxi. 1st ed. Praha: Triton 2008.

53. Somerfield J, Barber PA, Anderson NE, Kumar A, Spriggs D, Charleston A et al. Not all patients with atrial fibrillation-associated ischemic stroke can be started on anticoagulant therapy. Stroke 2006; 37(5): 1217–1220.

54. Nutescu EA, Shapiro NL, Chevalier A. New anticoagulant agents: direct thrombin inhibitors. Cardiol Clin 2008; 26(2): 169–187.

55. 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.

56. Eriksson BI, Kakkar AK, Turpie AGG, Gent M, ­Bandel TJ, Homering M et al. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg Br 2009; 91(8): 634–644.

57. Turpie AG. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008; 29(2): 155–165.

58. Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM. RECORD 4 Investigators. ­RECORD4 Study Investigators. Rivaroxaban – an oral, direct Factor Xa inhibitor – versus enoxaparin for thromboprophylaxis after total knee replacement. Lancet 2009; 373(9676): 1673–1680.

59. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb ­Haemost 2007; 5(11): 2178–2185.

60. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370(9591): 949–956.

61. Ginsberg JS, Davidson BL, Comp PC, Francis CW, ­Friedman RJ, Huo MH et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009; 24(1): 1–9.

62. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361(12): 1139–1151.

63. 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.

Labels
Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 5

2010 Issue 5

Most read in this issue

This topic is also in:


Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account