Skip to main content
Top
Published in:

Open Access 16-05-2024 | Aortic Valve Replacement | Review

Is There an Alternative Oral Anticoagulation to Vitamin-K-Antagonists for Patients with Mechanical Aortic Valve Replacement? – A Literature Review

Authors: Stephen Gerfer, Thorsten Wahlers, Elmar Kuhn

Published in: Cardiology and Therapy | Issue 3/2024

Login to get access

Abstract

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients’ perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement.
Literature
1.
go back to reference Dangas GD, Weitz JI, Giustino G, Makkar R, Mehran R. Prosthetic heart valve thrombosis. J Am Coll Cardiol. 2016;68(24):2670–89.CrossRefPubMed Dangas GD, Weitz JI, Giustino G, Makkar R, Mehran R. Prosthetic heart valve thrombosis. J Am Coll Cardiol. 2016;68(24):2670–89.CrossRefPubMed
2.
go back to reference Wiegner R, Chakraborty S, Huber-Lang M. Complement-coagulation crosstalk on cellular and artificial surfaces. Immunobiology. 2016;221(10):1073–9.CrossRefPubMed Wiegner R, Chakraborty S, Huber-Lang M. Complement-coagulation crosstalk on cellular and artificial surfaces. Immunobiology. 2016;221(10):1073–9.CrossRefPubMed
3.
go back to reference Jaffer IH, Stafford AR, Fredenburgh JC, Whitlock RP, Chan NC, Weitz JI. Dabigatran is less effective than warfarin at attenuating mechanical heart valve-induced thrombin generation. J Am Heart Assoc. 2015;4(8): e002322.CrossRefPubMedPubMedCentral Jaffer IH, Stafford AR, Fredenburgh JC, Whitlock RP, Chan NC, Weitz JI. Dabigatran is less effective than warfarin at attenuating mechanical heart valve-induced thrombin generation. J Am Heart Assoc. 2015;4(8): e002322.CrossRefPubMedPubMedCentral
4.
go back to reference Stavrou E, Schmaier AH. Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis. Thromb Res. 2010;125(3):210–5.CrossRefPubMedPubMedCentral Stavrou E, Schmaier AH. Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis. Thromb Res. 2010;125(3):210–5.CrossRefPubMedPubMedCentral
5.
go back to reference Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol. 2007;27(8):1687–93.CrossRefPubMed Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol. 2007;27(8):1687–93.CrossRefPubMed
7.
go back to reference Aimo A, Giugliano RP, De Caterina R. Non-vitamin K antagonist oral anticoagulants for mechanical heart valves: is the door still open? Circulation. 2018;138(13):1356–65.CrossRefPubMed Aimo A, Giugliano RP, De Caterina R. Non-vitamin K antagonist oral anticoagulants for mechanical heart valves: is the door still open? Circulation. 2018;138(13):1356–65.CrossRefPubMed
8.
go back to reference Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2021;143(5):e35–71.PubMed Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2021;143(5):e35–71.PubMed
10.
go back to reference Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89(2):635–41.CrossRefPubMed Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89(2):635–41.CrossRefPubMed
12.
go back to reference Orensky IA, Holdford DA. Predictors of noncompliance with warfarin therapy in an outpatient anticoagulation clinic. Pharmacotherapy. 2005;25(12):1801–8.CrossRefPubMed Orensky IA, Holdford DA. Predictors of noncompliance with warfarin therapy in an outpatient anticoagulation clinic. Pharmacotherapy. 2005;25(12):1801–8.CrossRefPubMed
13.
go back to reference Kimmel SE, Chen Z, Price M, Parker CS, Metlay JP, Christie JD, et al. The influence of patient adherence on anticoagulation control with warfarin: results from the international normalized ratio adherence and genetics (IN-RANGE) study. Arch Intern Med. 2007;167(3):229–35.CrossRefPubMed Kimmel SE, Chen Z, Price M, Parker CS, Metlay JP, Christie JD, et al. The influence of patient adherence on anticoagulation control with warfarin: results from the international normalized ratio adherence and genetics (IN-RANGE) study. Arch Intern Med. 2007;167(3):229–35.CrossRefPubMed
14.
go back to reference Butchart EG, Payne N, Li HH, Buchan K, Mandana K, Grunkemeier GL. Better anticoagulation control improves survival after valve replacement. J Thorac Cardiovasc Surg. 2002;123(4):715–23.CrossRefPubMed Butchart EG, Payne N, Li HH, Buchan K, Mandana K, Grunkemeier GL. Better anticoagulation control improves survival after valve replacement. J Thorac Cardiovasc Surg. 2002;123(4):715–23.CrossRefPubMed
15.
go back to reference Almeida Gde Q, Noblat Lde A, Passos LC, do Nascimento HF. Quality of life analysis of patients in chronic use of oral anticoagulant: an observational study. Health Qual Life Outcomes. 2011;9:91.CrossRefPubMed Almeida Gde Q, Noblat Lde A, Passos LC, do Nascimento HF. Quality of life analysis of patients in chronic use of oral anticoagulant: an observational study. Health Qual Life Outcomes. 2011;9:91.CrossRefPubMed
16.
go back to reference 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(12):1139–51.CrossRefPubMed 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(12):1139–51.CrossRefPubMed
17.
go back to reference Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefPubMed Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefPubMed
18.
go back to reference Proietti M, Romanazzi I, Romiti GF, Farcomeni A, Lip GYH. Real-world use of apixaban for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2018;49(1):98–106.CrossRefPubMed Proietti M, Romanazzi I, Romiti GF, Farcomeni A, Lip GYH. Real-world use of apixaban for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke. 2018;49(1):98–106.CrossRefPubMed
19.
go back to reference Eikelboom JE, Weitz JI. Dabigatran etexilate for prevention of venous thromboembolism. Thromb Haemost. 2009;101(1):2–4.CrossRefPubMed Eikelboom JE, Weitz JI. Dabigatran etexilate for prevention of venous thromboembolism. Thromb Haemost. 2009;101(1):2–4.CrossRefPubMed
20.
go back to reference Eriksson BI, Dahl OE, Buller HR, Hettiarachchi R, Rosencher N, Bravo ML, 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 BISTRO II randomized trial. J Thromb Haemost. 2005;3(1):103–11.CrossRefPubMed Eriksson BI, Dahl OE, Buller HR, Hettiarachchi R, Rosencher N, Bravo ML, 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 BISTRO II randomized trial. J Thromb Haemost. 2005;3(1):103–11.CrossRefPubMed
21.
go back to reference 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(6):1410–6.CrossRefPubMed 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(6):1410–6.CrossRefPubMed
22.
go back to reference Van de Werf F, Brueckmann M, Connolly SJ, Friedman J, Granger CB, Hartter 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.e1.CrossRefPubMed Van de Werf F, Brueckmann M, Connolly SJ, Friedman J, Granger CB, Hartter 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.e1.CrossRefPubMed
23.
go back to reference Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206–14.CrossRefPubMed Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206–14.CrossRefPubMed
24.
go back to reference Sharma S, Singh S. Dabigatran in patients with mechanical heart valves. N Engl J Med. 2014;370(4):381–2.CrossRefPubMed Sharma S, Singh S. Dabigatran in patients with mechanical heart valves. N Engl J Med. 2014;370(4):381–2.CrossRefPubMed
25.
go back to reference Hylek EM. Dabigatran and mechanical heart valves–not as easy as we hoped. N Engl J Med. 2013;369(13):1264–6.CrossRefPubMed Hylek EM. Dabigatran and mechanical heart valves–not as easy as we hoped. N Engl J Med. 2013;369(13):1264–6.CrossRefPubMed
26.
go back to reference Eikelboom JW, Brueckmann M, van de Werf F. Dabigatran versus warfarin in patients with mechanical heart valves: reply. J Thromb Haemost. 2014;12(3):426.CrossRefPubMed Eikelboom JW, Brueckmann M, van de Werf F. Dabigatran versus warfarin in patients with mechanical heart valves: reply. J Thromb Haemost. 2014;12(3):426.CrossRefPubMed
27.
go back to reference Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014;53(1):1–16.CrossRefPubMed Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014;53(1):1–16.CrossRefPubMed
28.
29.
go back to reference Kaeberich A, Reindl I, Raaz U, Maegdefessel L, Vogt A, Linde T, et al. Comparison of unfractionated heparin, low-molecular-weight heparin, low-dose and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study. J Thromb Thrombolysis. 2011;32(4):417–25.CrossRefPubMed Kaeberich A, Reindl I, Raaz U, Maegdefessel L, Vogt A, Linde T, et al. Comparison of unfractionated heparin, low-molecular-weight heparin, low-dose and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study. J Thromb Thrombolysis. 2011;32(4):417–25.CrossRefPubMed
30.
go back to reference Greiten LE, McKellar SH, Rysavy J, Schaff HV. Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model. Eur J Cardiothorac Surg. 2014;45(5):914–9.CrossRefPubMed Greiten LE, McKellar SH, Rysavy J, Schaff HV. Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model. Eur J Cardiothorac Surg. 2014;45(5):914–9.CrossRefPubMed
31.
go back to reference Duraes AR, Bitar YSL, Lima MLG, Santos CC, Schonhofen IS, Filho JAL, et al. Usefulness and safety of rivaroxaban in patients following isolated mitral valve replacement with a mechanical prosthesis. Am J Cardiol. 2018;122(6):1047–50.CrossRefPubMed Duraes AR, Bitar YSL, Lima MLG, Santos CC, Schonhofen IS, Filho JAL, et al. Usefulness and safety of rivaroxaban in patients following isolated mitral valve replacement with a mechanical prosthesis. Am J Cardiol. 2018;122(6):1047–50.CrossRefPubMed
32.
go back to reference Duraes AR, de Souza Lima Bitar Y, Filho JAL, Schonhofen IS, Camara EJN, Roever L, et al. Rivaroxaban versus warfarin in patients with mechanical heart valve: rationale and design of the RIWA study. Drugs RD. 2018;18(4):303–8.CrossRef Duraes AR, de Souza Lima Bitar Y, Filho JAL, Schonhofen IS, Camara EJN, Roever L, et al. Rivaroxaban versus warfarin in patients with mechanical heart valve: rationale and design of the RIWA study. Drugs RD. 2018;18(4):303–8.CrossRef
34.
go back to reference Roost E, Weber A, Alberio L, Englberger L, Reineke D, Keller D, et al. Rivaroxaban in patients with mechanical heart valves: a pilot study. Thromb Res. 2020;186:1–6.CrossRefPubMed Roost E, Weber A, Alberio L, Englberger L, Reineke D, Keller D, et al. Rivaroxaban in patients with mechanical heart valves: a pilot study. Thromb Res. 2020;186:1–6.CrossRefPubMed
35.
go back to reference 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(5):942–8.CrossRefPubMed 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(5):942–8.CrossRefPubMed
36.
go back to reference Jawitz OK, Wang TY, Lopes RD, Chavez A, Boyer B, Kim H, et al. Rationale and design of PROACT Xa: a randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X aortic heart valve. Am Heart J. 2020;227:91–9.CrossRefPubMedPubMedCentral Jawitz OK, Wang TY, Lopes RD, Chavez A, Boyer B, Kim H, et al. Rationale and design of PROACT Xa: a randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X aortic heart valve. Am Heart J. 2020;227:91–9.CrossRefPubMedPubMedCentral
37.
go back to reference Wang T, Svensson L, Wen J, Vekstein A, Gerdisch M, Rao V, et al. Apixaban or warfarin in patients with an On-X mechanical aortic valve. NEJM Evid. 2023;2(7):2300067.CrossRef Wang T, Svensson L, Wen J, Vekstein A, Gerdisch M, Rao V, et al. Apixaban or warfarin in patients with an On-X mechanical aortic valve. NEJM Evid. 2023;2(7):2300067.CrossRef
38.
go back to reference Mok CK, Boey J, Wang R, Chan TK, Cheung KL, Lee PK, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial. Circulation. 1985;72(5):1059–63.CrossRefPubMed Mok CK, Boey J, Wang R, Chan TK, Cheung KL, Lee PK, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial. Circulation. 1985;72(5):1059–63.CrossRefPubMed
40.
go back to reference Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb Haemost. 2003;1(7):1504–14.CrossRefPubMed Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb Haemost. 2003;1(7):1504–14.CrossRefPubMed
41.
go back to reference Chan NC, Weitz JI, Eikelboom JW. Anticoagulation for mechanical heart valves: will oral factor Xa inhibitors be effective? Arterioscler Thromb Vasc Biol. 2017;37(5):743–5.CrossRefPubMed Chan NC, Weitz JI, Eikelboom JW. Anticoagulation for mechanical heart valves: will oral factor Xa inhibitors be effective? Arterioscler Thromb Vasc Biol. 2017;37(5):743–5.CrossRefPubMed
42.
go back to reference Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, et al. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the “LOWERING-IT” Trial. Am Heart J. 2010;160(1):171–8.CrossRefPubMed Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, et al. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the “LOWERING-IT” Trial. Am Heart J. 2010;160(1):171–8.CrossRefPubMed
Metadata
Title
Is There an Alternative Oral Anticoagulation to Vitamin-K-Antagonists for Patients with Mechanical Aortic Valve Replacement? – A Literature Review
Authors
Stephen Gerfer
Thorsten Wahlers
Elmar Kuhn
Publication date
16-05-2024
Publisher
Springer Healthcare
Published in
Cardiology and Therapy / Issue 3/2024
Print ISSN: 2193-8261
Electronic ISSN: 2193-6544
DOI
https://doi.org/10.1007/s40119-024-00371-8

Other articles of this Issue 3/2024

Cardiology and Therapy 3/2024 Go to the issue

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

Keynote webinar | Spotlight on medication adherence

  • Webinar | 27-06-2024 | 18:00 (CEST)

Medication non-adherence is a major barrier to effective healthcare delivery; half of all patients do not follow their doctor’s recommendations or treatment plan.

Our experts explain the fundamentals with a practical discussion of how to manage non-adherence in two common scenarios: hypertension and asthma control.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Watch now