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Role of Novel Anticoagulants for Patients with Mechanical Heart Valves

  • Clinical Trials and Their Interpretations (JR Kizer, Section Editor)
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Abstract

The introduction of the target-specific oral anticoagulants (TSOACs) has led to a major shift in the management of patients at risk for thrombosis. The landscape continues to evolve as the evidence regarding their efficacy and safety in various clinical situations emerges. Antithrombotic therapy for thromboprophylaxis in patients with mechanical heart valves is challenging. To date, the RE-ALIGN trial comparing dabigatran etexilate to warfarin is the only randomized controlled study in this patient population. The higher risk of thromboembolic and bleeding events in the group of patients who received dabigatran compared with warfarin reinforced current guidelines recommending against the use of TSOACs in patients with mechanical heart valves. However, additional studies are needed to find suitable alternatives to vitamin K antagonists in this unique patient population.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Iung B, Vahanian A. Epidemiology of acquired valvular heart disease. Can J Cardiol. 2014 Mar 21.

  2. Sun JC, Davidson MJ, et al. Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends. Lancet. 2009;374(9689):565–76.

    Article  PubMed  Google Scholar 

  3. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS), Vahanian A, Alfieri O, Andreotti F. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33(19):2451–96. This paper provides an updated overview on the guidelines on the management of patients with valvular heart disease.

    Article  PubMed  Google Scholar 

  4. Hammermeister K, Sethi GK, et al. Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial. J Am Coll Cardiol. 2000;36(4):1152–58.

    Article  PubMed  CAS  Google Scholar 

  5. Pibarot, P. Dumesnil, JG. Valvular heart disease: changing concepts in disease management. Prosthetic heart valves selection of the optimal prosthesis and long-term management. Circulation 2009;2034–2048.

  6. Kulik A, Rubens FD, Wells PS, Kearon C, Mesana TG, van Berkom J, et al. Early postoperative anticoagulation after mechanical valve replacement: a systematic review. Ann Thorac Surg. 2006;81(2):770–81.

    Article  PubMed  Google Scholar 

  7. Bonow RO, Carabello BA, Chatterjee K, et al. 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. 2008;2008(118):e523–661.

    Google Scholar 

  8. Whitlock RP, Sun JC. Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th Ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e576S–600S. Updated guidelines for antithrombotic prophylaxis in patients with valvular disease.

    PubMed  CAS  PubMed Central  Google Scholar 

  9. Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prosthesis. Circulation. 1994;89:635–41.

    Article  PubMed  CAS  Google Scholar 

  10. Cannegieter FR, Rosendaal FR, et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Eng J Med. 1995;333:11–7.

    Article  CAS  Google Scholar 

  11. Acar J, Lung B, et al. AREVA: multicenter randomized comparison of low-dose versus standard-dose anticoagulation in patients with mechanical prosthetic heart valves. Circulation. 1996;94:2107–12.

    Article  PubMed  CAS  Google Scholar 

  12. Masl D, Little SH. Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis. J Am Coll Cardiol. 2001;37:569–78.

    Article  Google Scholar 

  13. Connolly SJ, Ezekowitz MD, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.

    Article  PubMed  CAS  Google Scholar 

  14. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342–52.

    Article  PubMed  CAS  Google Scholar 

  15. Schulman S1, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709–18. Randomized clinical trial comparing dabigatran to warfarin or placebo for extended thromboprophylaxis for venous thromboembolism.

    Article  PubMed  CAS  Google Scholar 

  16. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.

    Article  PubMed  CAS  Google Scholar 

  17. Granger CB, Alexander JK, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.

    Article  PubMed  CAS  Google Scholar 

  18. Ruff CT, Giugliano RF. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomized trials. Lancet. 2014;383:955–62. Meta-analysis including data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favorable risk-benefit profile.

    Article  PubMed  CAS  Google Scholar 

  19. The EINSTEIN investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.

    Article  Google Scholar 

  20. The EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366.

  21. Schulman S, Crowther MR. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood. 2012;119:3016–23.

    Article  PubMed  CAS  Google Scholar 

  22. Rojas-Hernandez C, Garcia DA. The novel oral anticoagulants. Semin Thromb Hemost. 2013;39:117–26. This article offers a critical review on the clinical indications of the target-specific oral anticoagulants.

    Article  PubMed  CAS  Google Scholar 

  23. Adcock-Funk DM. Pearls and pitfalls in the hematology lab: clotting and bleeding coagulation assays and anticoagulant monitoring. Hematology. 2012;2012:460–5.

    Google Scholar 

  24. Maegdefessel L, Linde T, et al. In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical valves. Thromb Res. 2010;126:196–200.

    Article  Google Scholar 

  25. Kaeberich A, Reindl I, et al. Comparison of unfractionated heparin, low-molecular-weight heparin and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study. J Thromb Thrombolysis. 2011;32:417–25.

    Article  PubMed  CAS  Google Scholar 

  26. McKellar SH, Abel S, et al. Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves. J Thorac Cardiovasc Surg. 2011;141:1410–6.

    Article  PubMed  CAS  Google Scholar 

  27. Greiten LE, McKellar SH, et al. Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model. Eur J Cardiothorac Surb. 2014;45:914–9.

    Article  Google Scholar 

  28. Shomburg JL, Medina EM, et al. Dabigatran versus warfarin after mechanical mitral valve replacement in the swine model. J Invest Surg. 2012;25:150–5.

    Article  Google Scholar 

  29. Stewart RA, Astell H, Young L, White HD. Thrombosis on a mechanical aortic valve whilst anti-coagulated with dabigatran. Heart Lung Circ. 2012;21:53–5.

    Article  PubMed  CAS  Google Scholar 

  30. Price J, Hynes M, Labinaz M, Ruel M, Boodhwani M. Mechanical valve thrombosis with dabigatran. J Am Coll Cardiol. 2012;60:1710–1.

    Article  PubMed  Google Scholar 

  31. Chu JW, Chen VH, Bunton R. Thrombosis of a mechanical heart valve despite dabigatran. Ann Intern Med. 2012;157:304.

    Article  PubMed  Google Scholar 

  32. Sharma S, Singh S, Sandhu R, Monterroso M, Bhambi N, Sharma R. Case report series of left atrial thrombus formation in patients on dabigatran therapy. Am J Ther. 2014;21(3):71–4.

    Article  Google Scholar 

  33. Van de Werf F, Brueckmann M, Connolly SJ, Friedman J, Granger CB, Härtter S, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). Am Heart J. 2012;163(6):931–7. This paper provides the rational background behind the design of the RE-ALIGN trial.

    Article  PubMed  Google Scholar 

  34. Eikelboom JW, Connolly SJ. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14. Clinical trial comparing dabigatran vs. warfarin in patients with mechanical heart valves.

    Article  PubMed  CAS  Google Scholar 

  35. Lee A, Rajaratnam R. The current and future role of the novel oral anticoagulants—indications beyond atrial fibrillation. Heart Lung Circ. 2014;23(1):2–9.

    Article  PubMed  Google Scholar 

  36. Hylek EM. Dabigatran and mechanical heart valves—not as easy as we hoped. N Engl J Med. 2013;369:1264–66. Review of the target specific oral anticoagulants for its approved and non-approved indications.

    Article  PubMed  CAS  Google Scholar 

  37. Drug safety communication: Pradaxa (dabigatran etexilate mesylate) should not be used in patients with mechanical prosthetic heart valves. Silver Spring, MD: Food and drug Administration, December 19, 2012 (http://www.fda.gov/Drugs/DrugSafety/ucm332912.htm).

  38. Summary of opinion (post authorization): Pradaxa (dabigatran etexilate). London: European Medicines Agency, December 12, 2012 (http://www.ema.europa.edu/docs/en_GB/document_library/Summary_of_opinion/human/000829/WC500136258.pdf).

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Peter Forsberg and Maria T. DeSancho declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Weill Cornell Medical College, Weill Greenberg Pavilion, 1305 York Avenue, 7th Floor Room 51, New York, NY, 10021, USA

    Peter Forsberg & Maria T. DeSancho

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  1. Peter Forsberg
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  2. Maria T. DeSancho
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Correspondence to Maria T. DeSancho.

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This article is part of the Topical Collection on Clinical Trials and Their Interpretations

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Forsberg, P., DeSancho, M.T. Role of Novel Anticoagulants for Patients with Mechanical Heart Valves. Curr Atheroscler Rep 16, 448 (2014). https://doi.org/10.1007/s11883-014-0448-7

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