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Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis

Abstract

Background and objectives

The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation.

Methods

Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65–74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin.

Results

The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m2. The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose.

Conclusions

Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

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References

  1. 1.

    Connoly SJ, Yusuf S, Eikelboom J, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.

    Article  Google Scholar 

  2. 2.

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

    CAS  Article  PubMed  Google Scholar 

  3. 3.

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

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–3014.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Bauersachs R, Berkowitz SD, et al.; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010; 363(26):2499–510.

  6. 6.

    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.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799–808.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Büller HR, Décousus H, Hokusai-VTE Investigators, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thrombembolism. N Engl J Med. 2013;10(369):1406–15.

    Google Scholar 

  9. 9.

    Jaffer IH, Stafford AR, Fredenburgh JC, et al. Dabigatran is less effective than warfarin at attenuating mechanical heart valve-induced thrombin generation. J Am Heart Assoc. 2015;4:e002322.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;26(369):1206–14.

    Article  Google Scholar 

  11. 11.

    Oxenham H, Bloomfield P, Wheatley DJ, et al. Twenty year comparison of a Bjork–Shiley mechanical heart valve with porcine bioprostheses. Heart. 2003;89:715–21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th edn: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e576S–600S.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Di Biase L, Trivedi C, Mohanty P, et al. Periprocedural and long term safety and feasibility of treatment with novel oral anticoagulants in patients with biological heart valve and atrial fibrillation (poster). J Am Coll Cardiol. 2015;65(10_S). doi:10.1016/S0735-1097(15)60355-2.

  14. 14.

    Molteni M, Plo FH, Primitz L, et al. The definition of valvular and non-valvular atrial fibrillation: results of a physicians’ survey. Europace. 2014;16:17205.

    Article  Google Scholar 

  15. 15.

    De Caterina R, Camm AJ. What is ‘valvular’ atrial fibrillation? A reappraisal. Eur Heart J. 2014;35:3328–35.

    Article  PubMed  Google Scholar 

  16. 16.

    Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806–17.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Breithardt G, Baumgartner H, Berkowitz SD, et al. Clinical characteristics and outcomes with rivaroxaban versus 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;35:3377–85.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Avezum A, Lopes RD, Schulte PJ, et al. Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular hearty disease: finding from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2015;132:624–32.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echodardiography. J Am Soc Echocardiogr. 2011;24:229–67.

    Article  PubMed  Google Scholar 

  20. 20.

    Pepi M, Evangelista A, Nihoyannopoulos P, et al. Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Ecocardiogr. 2010;11:461–76.

    Article  Google Scholar 

  21. 21.

    Heidbuchel H, Verhamme P, Alings M, et al. European Hearth Rhythm Association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625–51.

    Article  PubMed  Google Scholar 

  22. 22.

    Di Pasquale G, Mathieu G, Maggioni AP, et al. Current presentation and management of 7148 patients with atrial fibrillation in cardiology and internal medicine hospital centers: the ATA AF study. Int J Cardiol. 2013;167:2895–903.

    Article  PubMed  Google Scholar 

  23. 23.

    Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17:1467–507.

    Article  PubMed  Google Scholar 

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Corresponding author

Correspondence to Marco Matteo Ciccone.

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Funding

No funding was received for this study.

Conflicts of interest

Domenico Acanfora, Chiara Acanfora, Pietro Scicchitano, Marialaura Longobardi, Giuseppe Furgi, Gerardo Casucci, Bernardo Lanzillo, Ilaria Dentamaro, Annapaola Zito, Raffaele Antonelli Incalzi, and Marco Matteo Ciccone declare no conflicts of interest.

Ethical approval

This study was performed in accordance with the 1964 Helsinki declaration (and its amendments), and the Local Ethical Committee or institutional review board which approved the study.

Informed consent

Written informed consent was obtained from patients before enrolment.

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Acanfora, D., Acanfora, C., Scicchitano, P. et al. Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis. Clin Drug Investig 36, 857–862 (2016). https://doi.org/10.1007/s40261-016-0436-5

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Keywords

  • Atrial Fibrillation
  • Warfarin
  • Dabigatran
  • Rivaroxaban
  • Apixaban