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Can Direct Oral Anticoagulants Be Used for Stroke Prevention Among Patients with Valvular Atrial Fibrillation?

  • Invasive Electrophysiology and Pacing (EK Heist, Section Editor)
  • Published:
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Abstract

Purpose of Review

To review the clinical evidence underlying the efficacy and safety of the use of direct oral anticoagulants (DOACs) for the treatment of patients with valvular atrial fibrillation (AF).

Recent Findings

The recent focused update to the 2014 AHA/ACC/HRS Atrial Fibrillation Guidelines defines valvular AF as AF in the setting of moderate-to-severe mitral stenosis (MS) and/or in the presence of a mechanical heart valve. Landmark clinical trials of DOACs in patients with AF systematically excluded these patient populations. However, there are trial data in both animals and humans regarding the use of DOACs in patients with MS and in those with mechanical heart valves.

Summary

Based on sub-analyses and meta-analyses of clinical trial data in patients with AF, the use of DOACs in valvular AF is not recommended. Patients with moderate-to-severe MS or a mechanical heart valve and AF should be anticoagulated with dose-adjusted warfarin. DOACs are reasonable alternatives to warfarin in patients with AF and other types of valvular disease, including mild MS and bioprosthetic valves.

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References

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

  1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics – 2019 update: a report from the American Heart Association. Circulation. 2019;139:e56–e528. https://doi.org/10.1161/CIR.0000000000000659.

    Article  PubMed  Google Scholar 

  2. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110:1042–6. https://doi.org/10.1161/01.CIR.0000140263.20897.42.

    Article  PubMed  Google Scholar 

  3. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham Study. N Engl J Med. 1982;306:1018–22. https://doi.org/10.1056/NEJM198204293061703.

    Article  CAS  PubMed  Google Scholar 

  4. Benjamin EJ, Wolf PA, D’Agostino RB, Sibershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946–52. https://doi.org/10.1161/01.CIR.98.10.946.

    Article  CAS  PubMed  Google Scholar 

  5. Chugh SS, Blackshear JL, Shen WK, Hammill SC, Gersh BJ. Epidemiology and natural history of atrial fibrillation: clinical implications. J Am Coll Cardiol. 2001;37:371. https://doi.org/10.1016/S0735-1097(00)01107-4.

    Article  CAS  PubMed  Google Scholar 

  6. Patel NJ, Deshmukh A, Pant S, et al. Contemporary trends of hospitalization for atrial fibrillation in the United States, 2000 through 2010: implications for healthcare planning. Circulation. 2014;129:2371–9. https://doi.org/10.1161/CIRCULATIONAHA.114.008201.

    Article  PubMed  Google Scholar 

  7. •• January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2015 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2019;16(7. Updated guidelines that more clearly define valvular vs. non-valvular atrial fibrillation and provides recommendations based on the latest evidence):e66–93. https://doi.org/10.1016/j.hrthm.2019.01.024.

    Article  PubMed  Google Scholar 

  8. De Caterina R, Camm AJ. What is “valvular” atrial fibrillation? A reappraisal. Eur Heart J. 2014;35:3328–35. https://doi.org/10.1093/eurheartj/ehu352.

    Article  CAS  PubMed  Google Scholar 

  9. •• Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin III JP, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O’Gara PT, Rigolin VH, Sundt III TM, Thompson A 2017 ACC/AHA focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;70(2):252–289. https://doi.org/10.1161/CIR.0000000000000503. 9. Updated guidelines that more clearly define valvular vs. non-valvular atrial fibrillation and provides recommendations based on the latest evidence.

  10. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92. https://doi.org/10.1056/NEJMc1112500.

    Article  CAS  PubMed  Google Scholar 

  11. 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;361:1139–51. https://doi.org/10.1056/NEJMoa0905561.

    Article  CAS  PubMed  Google Scholar 

  12. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093–2104. DOI: https://doi.org/10.1056/NEJMoa1310907.

    Article  CAS  PubMed  Google Scholar 

  13. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91. https://doi.org/10.1056/NEJMc1112233.

    Article  CAS  PubMed  Google Scholar 

  14. Avezum A, Lopes RD, Schulte PJ, Lanas F, Gersh BJ, Hanna M, et al. Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular heart disease: findings from the apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial. Circulation. 2015;132:624–32. https://doi.org/10.1161/CIRCULATIONAHA.114.014807.

    Article  CAS  PubMed  Google Scholar 

  15. Vinereanu D, Wang A, Mulder H, Lopes RD, Jansky P, Lewis BS, et al. Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease. Heart. 2018;104(15):1292–9. https://doi.org/10.1136/heartjnl-2017-312272.

    Article  PubMed  Google Scholar 

  16. Ezekowitz MD, Nagarakanti R, Noack H, Brueckmann M, Litherland C, Jacobs M, et al. Comparison of dabigatran and warfarin in patients with atrial fibrillation and valvular heart disease: the RE-LY trial (randomized evaluation of long-term anticoagulant therapy). Circulation. 2016;134(8):589–98. https://doi.org/10.1161/CIRCULATIONAHA.115.020950.

    Article  CAS  PubMed  Google Scholar 

  17. De Caterina R, Renda G, Carnicelli AP, et al. Valvular heart disease patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial. J Am Coll Cardiol. 2017;69(11):1372–82. https://doi.org/10.1016/j.jacc.2016.12.031.

    Article  CAS  PubMed  Google Scholar 

  18. Breithardt G, Baumgartner H, Berkowitz SD, Hellkamp AS, Piccini JP, Stevens SR, et al. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial. Eur Heart J. 2014;35(47):3377–35. https://doi.org/10.1093/eurheartj/ehu305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Breithardt G, Baumgartner H, Berkowitz SD, Hellkamp AS, Piccini JP, Lokhnygina Y, et al. Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban. Heart. 2016;102:1036–43. https://doi.org/10.1136/heartjnl-2015-308120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Renda G, Ricci F, Giugliano RP, De Caterina R. Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease. J Am Coll Cardiol. 2017;69:1363–71. https://doi.org/10.1016/j.jacc.2016.12.038.

    Article  PubMed  Google Scholar 

  21. Pan KL, Singer DE, Ovbiagele B, Wu YL, Ahmed MA, Lee M. Effects of non-vitamin K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and valvular heart disease: a systematic review and meta-analysis. J Am Heart Assoc. 2017;6:e005835. https://doi.org/10.1161/JAHA.117.005835.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Caldeira D, David C, Costa J, Ferreira JJ, Pinto FJ. Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease: systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2018;4:111–8. https://doi.org/10.1093/ehjcvp/pvx028.

    Article  PubMed  Google Scholar 

  23. Duraes AR, de Souza RP, de Almeida NB, et al. Dabigatran versus warfarin after bioprosthesis valve replacement for the management of atrial fibrillation postoperatively: DAWA Pilot Study. Drugs RD. 2016;16:149–54. https://doi.org/10.1007/s40268-016-0124-1.

    Article  CAS  Google Scholar 

  24. Kim JY, Kim SH, Myong JP, et al. Outcomes of direct oral anticoagulants in patients with mitral stenosis. J Am Coll Cardiol. 2018;73:1123–31. https://doi.org/10.1016/j.jacc.2018.12.047.

    Article  CAS  Google Scholar 

  25. McKellar SH, Abel S, Camp CL, Suri RM, Ereth MH, Schaff HV. Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves. J Thorac Cardiovasc Surg. 2011;141:1410–6. https://doi.org/10.1016/j.jtcvs.2011.02.011.

    Article  CAS  PubMed  Google Scholar 

  26. Lester PA, Coleman DM, Diaz JA, Jackson TO, Hawley AE, Mathues AR, et al. Apixaban versus warfarin for mechanical heart valve thromboprophylaxis in a swine aortic heterotopic valve model. Arterioscler Thromb Vasc Biol. 2017;37:942–8. https://doi.org/10.1161/ATVBAHA.116.308649.

    Article  CAS  PubMed  Google Scholar 

  27. • Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med 2013;369:1206–1214. doi: https://doi.org/10.1111/jth.12500. 27. This is the only DOAC clinical trial in patients with mechanical heart valves.

    Article  CAS  PubMed  Google Scholar 

  28. Guimaraes PO, Pokorney SD, Lopes RD, et al. Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: insights from the ARISTOTLE trial. Clin Cardiol. 2019;42:568–71. https://doi.org/10.1002/clc.23178.

    Article  PubMed  PubMed Central  Google Scholar 

  29. An KR, Belley-Cote EP, Um KJ, Gupta S, McClure G, Jaffer I, et al. Antiplatelet therapy versus anticoagulation after surgical bioprosthetic aortic valve replacement: a systematic review and meta-analysis. Thromb Haemost. 2019;119:328–39. https://doi.org/10.1055/s-0038-1676816.

    Article  PubMed  Google Scholar 

  30. Papak JN, Chiovaro JC, Noelck N, Healy LD, Freeman M, Quin JA, et al. Antithrombotic strategies after bioprosthetic aortic valve replacement: a systematic review. Ann Thorac Surg. 2019;107:1571–81. https://doi.org/10.1016/j.athoracsur.2018.10.016.

    Article  PubMed  Google Scholar 

  31. Ahmad S, Wilt H. Stroke prevention in atrial fibrillation and valvular heart disease. Open Cardiovasc Med J. 2016;10:110–6. https://doi.org/10.2174/1874192401610010110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA

    Sarah L. Anderson & Joel C. Marrs

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Anderson, S.L., Marrs, J.C. Can Direct Oral Anticoagulants Be Used for Stroke Prevention Among Patients with Valvular Atrial Fibrillation?. Curr Cardiol Rep 21, 118 (2019). https://doi.org/10.1007/s11886-019-1199-4

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