Advance research of dabigatran Applying in Anticoagulation afer heart valve replacement_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

QIUJun-tao ,  LUOXin-jin

Department of Cardiovascular Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, P. R. China;

Corresponding?author：

LUOXin-jin, Email: luoxinjin@yahoo.com

Keywords：

Dabigatran; Heart valve replacement; Anticoagulation

DOI：

10.7507/1007-4848.20150127

Video：

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Recent clinical trials showed that dabigatran was superior to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation, however whether it is suitable for the lifelong anticoagulation in patients after heart valve replacement, remains controversial. Many animal experiments showed that dabigatran group was better than heparin and warfarin in the prevention of thrombosis and bleeding complications after valve replacement. Randomized, phaseⅡstudy to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN) clinical trial showed that dabigatran wasn't as effective as warfarin in preventing thrombosis, but increases the risk of bleeding. And there are some case reports about thrombosis and bleeding complications after taking dabigatran. At present, the efficacy and safety of dabigatran applying in patients after heart valve replacement still needs further study.

Citation： QIUJun-tao, LUOXin-jin. Advance research of dabigatran Applying in Anticoagulation afer heart valve replacement. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(5): 491-495. doi: 10.7507/1007-4848.20150127 Copy

1.	Ji J, Ji SY, Yang JA, et al. Ultrasound-targeted transfection of tissuetype plasminogen activator gene carried by albumin nanoparticles to dog myocardium to prevent thrombosis afer heart mechanical valve replacement. Int J Nanomedicine, 2012, 7:2911-2919.
2.	Rahimtoola S. Choice of prosthetic heart valve in adults:an update. J Am Coll Cardiol, 2010, 55(22):2413-2426.
3.	Koertke H, Zittermann A, Wagner O, et al. Telemedicine-guided very low-dose international normalized ratio self-control in patients with mechanical heart valve implants. Eur Heart J, 2014, Sep 9.[Epub ahead of print].
4.	Cannegieter SC, Rosendaal FR, Bri?t E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation, 1994, 89(2):635-641.
5.	Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamoleaspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism:a prospective randomized clinical trial. Circulation, 1985, 72(5):1059-1063.
6.	Roudaut R, Serri K, Laftte S. Trombosis of prosthetic heart valves:diagnosis and therapeutic considerations. Heart, 2007, 93(1):137-142.
7.	Pruthi RK. Review of the American College of Chest Physicians[2012] Guidelines for anticoagulation therapy and prevention of thrombosis. Semin Hematol, 2013, 50(3):251-258.
8.	Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline):a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Toracic Surgeons. J Am Coll Cardiol, 2011, 57(19):1920-1959.
9.	Sun JC, Davidson MJ, Lamy A, et al. Antithrombotic management of patients with prosthetic heart valves:current evidence and future trends. Lancet, 2009, 374(9689):565-576.
10.	Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases:a population-based study. Lancet, 2006, 368(9540):1005-1011.
11.	Carapetis JR, Steer AC, Mulholland EK, et al. Te global burden of group A streptococcal diseases. Lancet Infect Dis, 2005, 5(11):685-694.
12.	董力, 許建屏, 石應康.《瓣膜病術后抗凝個體化和低抗凝標準研究》階段研究進展.中國胸心血管外科臨床雜志, 2013, 20(1):1-2.
13.	Dincq AS, Lessire S, Douxfls J, et al. Management of non-vitamin K antagonist oral anticoagulants in the perioperative setting. Biomed Res Int, 2014:385014.
14.	Blommel ML, Blommel A. Dabigatran etexilate:a novel oral direct thrombin inhibitor. Am J Health Syst Pharm, 2011, 68(16):1506-1519.
15.	Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood, 2010, 115(1):15-20.
16.	Lu Y, Branstad R, Karim RM, et al. Consideration of clinical variables for choosing new anticoagulant alternatives to warfarin for the management of non-valvular atrial fbrillation. J Clin Pharm Ter, 2014, 39(6):628-636.
17.	Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med, 2009, 361(24):2342-2352.
18.	Eriksson BI, Dahl OE, Buller HR, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement:the BISTROⅡrandomized trial. J Tromb Haemost, 2005, 3(1):103-111.
19.	van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate——a novel, reversible, oral direct thrombin inhibitor:interpretation of coagulation assays and reversal of anticoagulant activity. Tromb Haemost, 2010, 103(6):1116-1127.
20.	Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos, 2008, 36(2):386-399.
21.	Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Tromb Hemost, 2009, 15(Suppl 1):9S-16S.
22.	Liesenfeld KH, Lehr T, Dansirikul C, et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fbrillation from the RE-LY trial. J Tromb Haemost, 2011, 9(11):2168-2175.
23.	Lehr T, Haertter S, Liesenfeld KH, et al. Dabigatran etexilate in atrial fbrillation patients with severe renal impairment:dose identifcation using pharmacokinetic modeling and simulation. J Clin Pharmacol, 2012, 52(9):1373-1378.
24.	Charlton B, Redberg R. The trouble with dabigatran. BMJ, 2014, 349:g4681.
25.	Aalbers J, Bryer A, Klug E. FDA committee unanimously recommends approval of dabigatran etexilate for stroke prevention in atrial fbrillation. Cardiovasc J Afr, 2010, 21(6):341.
26.	Maegdefessel L, Linde T, Krapiec F, et al. In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves. Tromb Res, 2010, 126(3):e196-e200.
27.	Maegdefessel L, Linde T, Michel T, et al. Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves, results of an in vitro study. Tromb Haemost, 2009, 101(6):1163-1169.
28.	McKellar SH, Abel S, Camp CL, et al. Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves. J Torac Cardiovasc Surg, 2011, 141(6):1410-1416.
29.	McKellar SH, Thompson JL, Schaff HV. A model of heterotopic aortic valve replacement for studying thromboembolism prophylaxis in mechanical valve prostheses. J Surg Res, 2007, 141(1):1-6.
30.	Schomburg JL, Medina EM, Lahti MT, et al. Dabigatran versus warfarin after mechanical mitral valve replacement in the swine model. J Invest Surg, 2012, 25(3):150-155.
31.	Van de Werf F, Brueckmann M, Connolly SJ, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves:Te randomized, phaseⅡstudy to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients afer heart valve replacement (RE-ALIGN). Am Heart J, 2012, 163(6):931-937.
32.	Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med, 2013, 369(13):1206-1214.
33.	朱亞彬, 江書胤, 王寧夫, 等.達比加群對冠狀動脈支架植入術后行瓣膜置換術患者的抗凝效果.蘇州大學學報, 2012, 32(3):390-393.
34.	Kuwauchi S, Watanabe S, Abe K, et al. Thromboembolism in a patient with a mechanical mitral valve during anticoagulation with dabigatran etexilate. Ann Torac Surg, 2013, 96(5):1863-1864.
35.	Akgüllü C, Ery?lmaz U, Kurto?lu T. Severe thrombosis of bioprosthesis mitral valve afer dabigatran. Turk Kardiyol Dern Ars, 2013, 41(6):529-533.
36.	Stewart RA, Astell H, Young L, et al. Trombosis on a mechanical aortic valve whilst anti-coagulated with dabigatran. Heart Lung Circ, 2012, 21(1):53-55.
37.	Price J, Hynes M, Labinaz M, et al. Mechanical valve thrombosis with dabigatran. J Am Coll Cardiol, 2012, 60(17):1710-1711.
38.	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.
39.	Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identifed events in the RE-LY trial. N Engl J Med, 2010, 363(19):1875-1876.
40.	Zough F, Tafreshi J, Pai RG. Dabigatran use in mechanical heart valve patients. Future Cardiol, 2014, 10(1):19-22.
41.	Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fbrillation:Virchow's triad revisited. Lancet, 2009, 373(9658):155-166.
42.	Dewanjee MK, Gross DR, Zhai P, et al. Trombogenicity of polyethylene oxidebonded Dacron sewing ring in a mechanical heart valve. J Heart Valve Dis, 1999, 8(3):324-330.
43.	刁明強, 董力, 江虹, 等.心臟機械瓣膜置換術后早期抗凝的方法分析.中國胸心血管外科臨床雜志, 2006, 13(1):10-13.
44.	Fallon AM, Goodchild TT, Cox JL, et al. In vivo remodeling potential of a novel bioprosthetic tricuspid valve in an ovine model. J Torac Cardiovasc Surg, 2014, 148(1):333-340.
45.	Majeed A, Hwang HG, Connolly SJ, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation, 2013, 128(21):2325-2332.
46.	Faraoni D, Samama CM, Ranucci M, et al. Perioperative management of patients receiving new oral anticoagulants:an international survey. Clin Lab Med, 2014, 34(3):637-654.

1. Ji J, Ji SY, Yang JA, et al. Ultrasound-targeted transfection of tissuetype plasminogen activator gene carried by albumin nanoparticles to dog myocardium to prevent thrombosis afer heart mechanical valve replacement. Int J Nanomedicine, 2012, 7:2911-2919.
2. Rahimtoola S. Choice of prosthetic heart valve in adults:an update. J Am Coll Cardiol, 2010, 55(22):2413-2426.
3. Koertke H, Zittermann A, Wagner O, et al. Telemedicine-guided very low-dose international normalized ratio self-control in patients with mechanical heart valve implants. Eur Heart J, 2014, Sep 9.[Epub ahead of print].
4. Cannegieter SC, Rosendaal FR, Bri?t E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation, 1994, 89(2):635-641.
5. Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamoleaspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism:a prospective randomized clinical trial. Circulation, 1985, 72(5):1059-1063.
6. Roudaut R, Serri K, Laftte S. Trombosis of prosthetic heart valves:diagnosis and therapeutic considerations. Heart, 2007, 93(1):137-142.
7. Pruthi RK. Review of the American College of Chest Physicians[2012] Guidelines for anticoagulation therapy and prevention of thrombosis. Semin Hematol, 2013, 50(3):251-258.
8. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline):a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Toracic Surgeons. J Am Coll Cardiol, 2011, 57(19):1920-1959.
9. Sun JC, Davidson MJ, Lamy A, et al. Antithrombotic management of patients with prosthetic heart valves:current evidence and future trends. Lancet, 2009, 374(9689):565-576.
10. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases:a population-based study. Lancet, 2006, 368(9540):1005-1011.
11. Carapetis JR, Steer AC, Mulholland EK, et al. Te global burden of group A streptococcal diseases. Lancet Infect Dis, 2005, 5(11):685-694.
12. 董力, 許建屏, 石應康.《瓣膜病術后抗凝個體化和低抗凝標準研究》階段研究進展.中國胸心血管外科臨床雜志, 2013, 20(1):1-2.
13. Dincq AS, Lessire S, Douxfls J, et al. Management of non-vitamin K antagonist oral anticoagulants in the perioperative setting. Biomed Res Int, 2014:385014.
14. Blommel ML, Blommel A. Dabigatran etexilate:a novel oral direct thrombin inhibitor. Am J Health Syst Pharm, 2011, 68(16):1506-1519.
15. Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood, 2010, 115(1):15-20.
16. Lu Y, Branstad R, Karim RM, et al. Consideration of clinical variables for choosing new anticoagulant alternatives to warfarin for the management of non-valvular atrial fbrillation. J Clin Pharm Ter, 2014, 39(6):628-636.
17. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med, 2009, 361(24):2342-2352.
18. Eriksson BI, Dahl OE, Buller HR, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement:the BISTROⅡrandomized trial. J Tromb Haemost, 2005, 3(1):103-111.
19. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate——a novel, reversible, oral direct thrombin inhibitor:interpretation of coagulation assays and reversal of anticoagulant activity. Tromb Haemost, 2010, 103(6):1116-1127.
20. Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos, 2008, 36(2):386-399.
21. Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Tromb Hemost, 2009, 15(Suppl 1):9S-16S.
22. Liesenfeld KH, Lehr T, Dansirikul C, et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fbrillation from the RE-LY trial. J Tromb Haemost, 2011, 9(11):2168-2175.
23. Lehr T, Haertter S, Liesenfeld KH, et al. Dabigatran etexilate in atrial fbrillation patients with severe renal impairment:dose identifcation using pharmacokinetic modeling and simulation. J Clin Pharmacol, 2012, 52(9):1373-1378.
24. Charlton B, Redberg R. The trouble with dabigatran. BMJ, 2014, 349:g4681.
25. Aalbers J, Bryer A, Klug E. FDA committee unanimously recommends approval of dabigatran etexilate for stroke prevention in atrial fbrillation. Cardiovasc J Afr, 2010, 21(6):341.
26. Maegdefessel L, Linde T, Krapiec F, et al. In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves. Tromb Res, 2010, 126(3):e196-e200.
27. Maegdefessel L, Linde T, Michel T, et al. Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves, results of an in vitro study. Tromb Haemost, 2009, 101(6):1163-1169.
28. McKellar SH, Abel S, Camp CL, et al. Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves. J Torac Cardiovasc Surg, 2011, 141(6):1410-1416.
29. McKellar SH, Thompson JL, Schaff HV. A model of heterotopic aortic valve replacement for studying thromboembolism prophylaxis in mechanical valve prostheses. J Surg Res, 2007, 141(1):1-6.
30. Schomburg JL, Medina EM, Lahti MT, et al. Dabigatran versus warfarin after mechanical mitral valve replacement in the swine model. J Invest Surg, 2012, 25(3):150-155.
31. Van de Werf F, Brueckmann M, Connolly SJ, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves:Te randomized, phaseⅡstudy to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients afer heart valve replacement (RE-ALIGN). Am Heart J, 2012, 163(6):931-937.
32. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med, 2013, 369(13):1206-1214.
33. 朱亞彬, 江書胤, 王寧夫, 等.達比加群對冠狀動脈支架植入術后行瓣膜置換術患者的抗凝效果.蘇州大學學報, 2012, 32(3):390-393.
34. Kuwauchi S, Watanabe S, Abe K, et al. Thromboembolism in a patient with a mechanical mitral valve during anticoagulation with dabigatran etexilate. Ann Torac Surg, 2013, 96(5):1863-1864.
35. Akgüllü C, Ery?lmaz U, Kurto?lu T. Severe thrombosis of bioprosthesis mitral valve afer dabigatran. Turk Kardiyol Dern Ars, 2013, 41(6):529-533.
36. Stewart RA, Astell H, Young L, et al. Trombosis on a mechanical aortic valve whilst anti-coagulated with dabigatran. Heart Lung Circ, 2012, 21(1):53-55.
37. Price J, Hynes M, Labinaz M, et al. Mechanical valve thrombosis with dabigatran. J Am Coll Cardiol, 2012, 60(17):1710-1711.
38. 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.
39. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identifed events in the RE-LY trial. N Engl J Med, 2010, 363(19):1875-1876.
40. Zough F, Tafreshi J, Pai RG. Dabigatran use in mechanical heart valve patients. Future Cardiol, 2014, 10(1):19-22.
41. Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fbrillation:Virchow's triad revisited. Lancet, 2009, 373(9658):155-166.
42. Dewanjee MK, Gross DR, Zhai P, et al. Trombogenicity of polyethylene oxidebonded Dacron sewing ring in a mechanical heart valve. J Heart Valve Dis, 1999, 8(3):324-330.
43. 刁明強, 董力, 江虹, 等.心臟機械瓣膜置換術后早期抗凝的方法分析.中國胸心血管外科臨床雜志, 2006, 13(1):10-13.
44. Fallon AM, Goodchild TT, Cox JL, et al. In vivo remodeling potential of a novel bioprosthetic tricuspid valve in an ovine model. J Torac Cardiovasc Surg, 2014, 148(1):333-340.
45. Majeed A, Hwang HG, Connolly SJ, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation, 2013, 128(21):2325-2332.
46. Faraoni D, Samama CM, Ranucci M, et al. Perioperative management of patients receiving new oral anticoagulants:an international survey. Clin Lab Med, 2014, 34(3):637-654.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Advance research of dabigatran Applying in Anticoagulation afer heart valve replacement

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