Journal of Thrombosis and Thrombolysis

, Volume 31, Issue 4, pp 514–522 | Cite as

Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician

  • Tiago L. L. Leiria
  • Renato D. Lopes
  • Judson B. Williams
  • Jason N. Katz
  • Renato A. K. Kalil
  • John H. AlexanderEmail author


Patients with prosthetic heart valves require chronic oral anticoagulation. In this clinical scenario, physicians must be mindful of the thromboembolic and bleeding risks related to chronic anticoagulant therapy. Currently, only vitamin K antagonists are approved for this indication. This paper reviews the main heart valve guidelines focusing on the use of oral anticoagulation in these patients.


Heart valves Anticoagulation Vitamin K antagonist Warfarin Guidelines 


  1. 1.
    Lloyd-Jones D, Adams RJ, Brown TM et al (2010) Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121:948–954PubMedCrossRefGoogle Scholar
  2. 2.
    Leon MB, Smith CR, Mack M et al (2010) Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 363:1597–1607PubMedCrossRefGoogle Scholar
  3. 3.
    Prandoni A (1942) The anticoagulants heparin and the dicoumarin 3,3′-methylene-bis-(4-hydroxycoumarin). Bull N Y Acad Med 18:433–458PubMedGoogle Scholar
  4. 4.
    Oliva Berini E, Galan Alvarez P, Pacheco Onrubia AM (2008) Comparison of quality and hemorragic risk of oral anticoagulant therapy using acenocoumarol versus warfarin. Med Clin (Barc) 131:96–97CrossRefGoogle Scholar
  5. 5.
    Jensen CF, Christensen TD, Maegaard M, Hasenkam JM (2009) Quality of oral anticoagulant therapy in patients who perform self management: warfarin versus phenprocoumon. J Thromb Thrombolysis 28:276–281PubMedCrossRefGoogle Scholar
  6. 6.
    Fihn SD, Gad isseur AA, Pasterkamp E et al (2003) Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon. Thromb Haemost 90:260–266PubMedGoogle Scholar
  7. 7.
    Leiria TL, Pellanda L, Miglioranza MH et al (2010) Warfarin and phenprocoumon: experience of an outpatient anticoagulation clinic. Arq Bras Cardiol 94:41–45PubMedCrossRefGoogle Scholar
  8. 8.
    Petersen P, Grind M, Adler J (2003) Ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. SPORTIF II: a dose-guiding, tolerability, and safety study. J Am Coll Cardiol 41:1445–1451PubMedCrossRefGoogle Scholar
  9. 9.
    Rieder MJ, Reiner AP, Gage BF et al (2005) Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 352:2285–2293PubMedCrossRefGoogle Scholar
  10. 10.
    Schwarz UI, Ritchie MD, Bradford Y et al (2008) Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 358:999–1008PubMedCrossRefGoogle Scholar
  11. 11.
    Cadamuro J, Dieplinger B, Felder T et al (2010) Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements. Eur J Clin Pharmacol 66:253–260PubMedCrossRefGoogle Scholar
  12. 12.
    Kakar P, Lane D, Lip GY (2006) Bleeding risk stratification models in deciding on anticoagulation in patients with atrial fibrillation: a useful complement to stroke risk stratification schema. Chest 130:1296–1299PubMedGoogle Scholar
  13. 13.
    Kuijer PM, Hutten BA, Prins MN, Buller HR (1999) Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 159:457–460PubMedCrossRefGoogle Scholar
  14. 14.
    Palareti G, Leali N, Coccheri S et al (1996) Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 348:423–428PubMedCrossRefGoogle Scholar
  15. 15.
    Fang MC, Chang Y, Hylek EM et al (2004) Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 141:745–752PubMedGoogle Scholar
  16. 16.
    Beyth RJ, Quinn LM, Landefeld CS (1998) Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 105:91–99PubMedCrossRefGoogle Scholar
  17. 17.
    Cannegieter SC, Rosendaal FR, Briet E (1994) Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 89:635–641PubMedGoogle Scholar
  18. 18.
    Cannegieter SC, Rosendaal FR, Wintzen AR et al (1995) Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 333:11–17PubMedCrossRefGoogle Scholar
  19. 19.
    Dasi LP, Simon HA, Sucosky P, Yoganathan AP (2009) Fluid mechanics of artificial heart valves. Clin Exp Pharmacol Physiol 36:225–237PubMedCrossRefGoogle Scholar
  20. 20.
    ElBardissi AW, DeBardino DJ, Chen FY, Yamashita MH, Cohn LH (2010) Is early antithrombotic therapy necessary in patients with bioprosthetic aortic valves in normal sinus rhythm? J Thorac Cardiovasc Surg 139:1137–1145PubMedCrossRefGoogle Scholar
  21. 21.
    Baudet EM, Puel V, McBride JT et al (1995) Long-term results of valve replacement with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 109:858–870PubMedCrossRefGoogle Scholar
  22. 22.
    Bjork VO, Henze A (1975) Management of thrombo-embolism after aortic valve replacement with the Bjork-Shiley tilting disc valve. Medicamental prevention with dicumarol in comparison with dipyridamole—acetylsalicylic acid. Surgical treatment of prosthetic thrombosis. Scand J Thorac Cardiovasc Surg 9:183–191PubMedGoogle Scholar
  23. 23.
    Torn M, Cannegieter SC, Bollen WL et al (2009) Optimal level of oral anticoagulant therapy for the prevention of arterial thrombosis in patients with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction: a prospective study of 4202 patients. Arch Intern Med 169:1203–1209PubMedCrossRefGoogle Scholar
  24. 24.
    Acar J, Iung B, Boissel JP et al (1996) AREVA: multicenter randomized comparison of low-dose versus standard-dose anticoagulation in patients with mechanical prosthetic heart valves. Circulation 94:2107–2112PubMedGoogle Scholar
  25. 25.
    Hering D, Piper C, Bergemann R et al (2005) Thromboembolic and bleeding complications following St. Jude medical valve replacement: results of the German experience with low-intensity anticoagulation study. Chest 127:53–59PubMedCrossRefGoogle Scholar
  26. 26.
    Massel D, Little SH (2001) Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis. J Am Coll Cardiol 37:569–578PubMedCrossRefGoogle Scholar
  27. 27.
    Larson RJ, Fisher ES (2004) Should aspirin be continued in patients started on warfarin? J Gen Intern Med 19:879–886PubMedCrossRefGoogle Scholar
  28. 28.
    Turpie AG, Gent M, Laupacis A et al (1993) A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med 329:524–529PubMedCrossRefGoogle Scholar
  29. 29.
    Little SH, Massel DR (2003) Antiplatelet and anticoagulation for patients with prosthetic heart valves. Cochrane Database Syst Rev 4:CD003464PubMedGoogle Scholar
  30. 30.
    Manzano-Fernandez S, Marin F, Pastor-Perez FJ et al (2008) Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting. Chest 134:559–567PubMedCrossRefGoogle Scholar
  31. 31.
    Rogacka R, Chieffo A, Michev I et al (2008) Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oral anticoagulation. JACC Cardiovasc Interv 1:56–61PubMedCrossRefGoogle Scholar
  32. 32.
    Salem DN, O’Gara PT, Madias C, Pauker SG (2008) Valvular and structural heart disease: American college of chest physicians evidence-based clinical practice guidelines (8th edn). Chest 133:593S–629SPubMedCrossRefGoogle Scholar
  33. 33.
    Vahanian A, Baumgartner H, Bax J et al (2007) Guidelines on the management of valvular heart disease: the task force on the management of valvular heart disease of the European society of cardiology. Eur Heart J 28:230–268PubMedGoogle Scholar
  34. 34.
    Triple Therapy in Patients on Oral Anticoagulation after Drug Eluting Stent Implantation (ISAR-TRIPLE). Identifier: NCT00776633. Accessed 14 Jan 2011Google Scholar
  35. 35.
    Schlitt A, Hauroeder B, Buerke M et al (2002) Effects of combined therapy of clopidogrel and aspirin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model. Thromb Res 107:39–43PubMedCrossRefGoogle Scholar
  36. 36.
    McKellar SH, Thompson JL III, Garcia-Rinaldi RF, Macdonald RJ, Sundt TM III, Schaff HV (2008) Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves: an in vivo study in swine. J Thorac Cardiovasc Surg 136:908–914PubMedCrossRefGoogle Scholar
  37. 37.
    Butany J, Ahluwalia MS, Munroe C et al (2003) Mechanical heart valve prostheses: identification and evaluation. Cardiovasc Pathol 12:1–22PubMedCrossRefGoogle Scholar
  38. 38.
    Gherli T, Colli A, Fragnito C et al (2004) Comparing warfarin with aspirin after biological aortic valve replacement: a prospective study. Circulation 110:496–500PubMedCrossRefGoogle Scholar
  39. 39.
    Colli A, Verhoye JP, Heijmen R et al (2008) Antithrombotic therapy after bioprosthetic aortic valve replacement: ACTION registry survey results. Eur J Cardiothorac Surg 33:531–536PubMedCrossRefGoogle Scholar
  40. 40.
    Colli A, D’Amico R, Mestres CA et al (2010) Is early antithrombotic therapy necessary after tissue mitral valve replacement? J Heart Valve Dis 19:405–411PubMedGoogle Scholar
  41. 41.
    Aramendi JI, Mestres CA, Martinez-Leon J, Campos V, Munoz G, Navas C (2005) Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (trac): prospective, randomized, co-operative trial. Eur J Cardiothorac Surg 27:854–860PubMedCrossRefGoogle Scholar
  42. 42.
    Kearon C, Hirsh J (1997) Management of anticoagulation before and after elective surgery. N Engl J Med 336:1506–1511PubMedCrossRefGoogle Scholar
  43. 43.
    Bonow RO, Carabello BA, Chatterjee K et al (2008) 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 118:e523–e661PubMedCrossRefGoogle Scholar
  44. 44.
    Bonow RO, Carabello BA, Kanu C et al (2006) ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation 114:e84–e231PubMedCrossRefGoogle Scholar
  45. 45.
    Garcia DA, Regan S, Henault LE et al (2008) Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med 168:63–69PubMedCrossRefGoogle Scholar
  46. 46.
    Wijdicks EF, Schievink WI, Brown RD, Mullany CJ et al (1998) The dilemma of discontinuation of anticoagulation therapy for patients with intracranial hemorrhage and mechanical heart valves. Neurosurgery 42:769–773PubMedCrossRefGoogle Scholar
  47. 47.
    Babikian VL, Kase CS, Pessin MS, Caplan LR, Gorelick PB (1988) Resumption of anticoagulation after intracranial bleeding in patients with prosthetic heart valves. Stroke 19:407–408PubMedGoogle Scholar
  48. 48.
    Roudaut R, Lafitte S, Roudeaut MF et al (2009) Management of prosthetic heart valve obstruction: fibrinolysis versus surgery. Early results and long-term follow-up in a single-centre study of 263 cases. Arch Cardiovasc Dis 102:269–277PubMedCrossRefGoogle Scholar
  49. 49.
    Gupta D, Kothari SS, Bahl VK et al (2000) Thrombolytic therapy for prosthetic valve thrombosis: short- and long-term results. Am Heart J 140:906–916PubMedCrossRefGoogle Scholar
  50. 50.
    Caceres-Loriga FM, Perez-Lopez H, Morlans-Hernandez K et al (2006) Thrombolysis as first choice therapy in prosthetic heart valve thrombosis. A study of 68 patients. J Thromb Thrombolysis 21:185–190PubMedCrossRefGoogle Scholar
  51. 51.
    Karthikeyan G, Math RS, Mathew N et al (2009) Accelerated infusion of streptokinase for the treatment of left-sided prosthetic valve thrombosis: a randomized controlled trial. Circulation 120:1108–1114PubMedCrossRefGoogle Scholar
  52. 52.
    Yusuf S, Zhao F, Mehta SR et al (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502PubMedCrossRefGoogle Scholar
  53. 53.
    Kulik A, Le May M, Wells GA, Mesana TG, Ruel M (2005) The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]. Curr Control Trials Cardiovasc Med 6:15PubMedCrossRefGoogle Scholar
  54. 54.
    CAPRIE Steering Committee (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348:1329–1339CrossRefGoogle Scholar
  55. 55.
    Sun JC, Davidson MJ, Lamy A, Eikelboom JW (2009) Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends. Lancet 374:565–576PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Tiago L. L. Leiria
    • 1
  • Renato D. Lopes
    • 2
  • Judson B. Williams
    • 3
  • Jason N. Katz
    • 4
  • Renato A. K. Kalil
    • 1
    • 5
  • John H. Alexander
    • 2
    Email author
  1. 1.Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de CardiologiaPorto AlegreBrazil
  2. 2.Duke Clinical Research Institute, Division of Cardiology, Department of MedicineDuke University Medical CenterDurhamUK
  3. 3.Duke Clinical Research Institute, Division of Cardiovascular and Thoracic Surgery, Department of SurgeryDuke University Medical CenterDurhamUK
  4. 4.Division of Cardiology & Division of Pulmonary/Critical Care MedicineUniversity of North Carolina Center for Heart and Vascular CareChapel HillUK
  5. 5.Universidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil

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