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Italian intersociety consensus on DOAC use in internal medicine

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Abstract

The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events. This document represents a consensus paper on the use of DOACs by representatives of three Italian scientific societies: the Italian Society of Internal Medicine (SIMI), the Federation of the Associations of Hospital Managers (FADOI), and the Society for the Study of Haemostasis and Thrombosis (SISET). This document formulates expert opinion guidance for pragmatic managing, monitoring and reversing the anticoagulant effect of DOACs in both chronic and emergency settings. This practical guidance may help the internist to create adequate protocols for patients hospitalized ion internal medicine wards, where patients are often elderly subjects affected by poly-morbidities and renal insufficiency, and, thus, require particular attention to drug–drug interactions and peri-procedural protocols.

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Acknowledgements

The assistance of Amanda Mannucci in the preparation of final draft is acknowledged. The authors thank the Presidents of the three Societies participating in this Consensus: Francesco Perticone, President of SIMI (Italian Society of Internal Medicine); Mauro Campanini, President of FADOI (Federation of Associations of Hospital Doctors on Internal Medicine); Anna Falanga, President of SISET (Italian Society for the Study of Haemostasis and Thrombosis).

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Authors and Affiliations

  1. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Domenico Prisco

  2. Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy

    Walter Ageno & Francesco Dentali

  3. Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy

    Cecilia Becattini

  4. Coagulation Service and Thrombosis Research Unit, Scientific Institute San Raffaele, Milan, Italy

    Armando D’Angelo

  5. Clinica Medica, Department of Medicine and Aging Sciences, University of Chieti G.D’Annunzio, Chieti, Italy

    Giovanni Davì & Francesca Santilli

  6. Institute of Internal Medicine and Geriatrics, Center for Haemorrhagic and Thrombotic Diseases, Haematology, Foundation Policlinico universitario “Agostino Gemelli”, Catholic University of the Sacred Heart, Rome, Italy

    Raimondo De Cristofaro

  7. Clinica Medica, Department of Clinical Medicine and Surgery, AOU Policlinico Federico II, Naples, Italy

    Giovanni Di Minno & Antonella Tufano

  8. Department of Immunohematology and Transfusion Medicine, and the Thrombosis and Hemostasis Center, Hospital Papa Giovanni XXIII, Bergamo, Italy

    Anna Falanga

  9. Department of Clinical Research, FADOI, Milan, Italy

    Gualberto Gussoni

  10. Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy

    Luca Masotti

  11. Cardiovascular Diseases, University of Bologna, Bologna, Italy

    Gualtiero Palareti

  12. Department of Internal Medicine and Medical Specialties, “La Sapienza” University of Rome, Rome, Italy

    Pasquale Pignatelli & Francesco Violi

  13. Haemostasis and Thrombosis Unit, Haematology, Az. Osp. “SS.Antonio e Biagio e C. Arrigo”, Alessandria, Italy

    Roberto M. Santi

  14. Internal Medicine Unit A - Ospedale Maggiore, AUSL Bologna, Bologna, Italy

    Mauro Silingardi

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  1. Domenico Prisco
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  2. Walter Ageno
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  3. Cecilia Becattini
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  9. Anna Falanga
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  10. Gualberto Gussoni
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  12. Gualtiero Palareti
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  13. Pasquale Pignatelli
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  14. Roberto M. Santi
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  18. Francesco Violi
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SIMI (Italian Society of Internal Medicine)

FADOI (Federation of Associations of Hospital Doctors on Internal Medicine)

SISET (Italian Society for the Study of Haemostasis and Thrombosis)

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Correspondence to Domenico Prisco.

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Conflict of interest

DP declares fees for participations in editorial boards and lectures by Bayer, Boehringer Ingelheim, BMS-Pfizer and Daiichi Sankyo given to his Institution. WA declares research support by Bayer and Boehringer Ingelheim; he also declare participation in advisory boards for Bayer, Boehringer Ingelheim, Daiichi Sankyo and BMS-Pfizer. CB declares speakers’ fees by Bayer, Bristol Meyer Squibb and Boehringer Ingelheim. AD declares speakers’ fees by Bayer, Boehringer Ingelheim, BMS-Pfizer and Daiichi Sankyo given to his Institution. FD declares a consultance activity for Bayer and Boehringer Ingelheim and participations in advisory boards of Boehringer Ingelheim, BMS-Pfizer. AF declare a role of speakers’ bureau for Pfizer, Aspen and Rovi. GP declares participation in advisory board or speakers’ fees by Alfa-Wassermann, Daiichi-Sankyo, Pfizer, Roche, Siemens and Werfen. PP declares speakers’ fees by Bayer, Boehringer Ingelheim, BMS-Pfizer and Daiichi Sankyo FS declares fesearch support by Bayer. GD, RD, GDM, GG, LM, RMS, MS, AT, FV declare that they have no conflict of interest.

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

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Additional information

Members of SIMI (Italian Society of Internal Medicine), FADOI (Federation of Associations of Hospital Doctors on Internal Medicine) and SISET (Italian Society for the Study of Haemostasis and Thrombosis) are listed in Acknowledgement.

Appendix

Appendix

Trial

Exclusion criteria

RELY

History of heart valve disorder (i.e. prosthetic valve or hemodynamically relevant valve disease)

ROCKET

Hemodynamically significant mitral valve stenosis. Prosthetic heart valve. Annuloplasty with or without prosthetic ring, commissurotomy, or valvuloplasty permitted

Planned invasive procedure with potential for uncontrolled bleeding, including major surgery (i.e. heart valve surgery)

ARISTOTELE

Moderate or severe mitral stenosis, conditions other than atrial fibrillation that require anticoagulation (e.g. a prosthetic heart valve)

ENGAGE AF

Moderate or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve (subjects with bioprosthetic heart valves or valve repair could be included)

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Prisco, D., Ageno, W., Becattini, C. et al. Italian intersociety consensus on DOAC use in internal medicine. Intern Emerg Med 12, 387–406 (2017). https://doi.org/10.1007/s11739-017-1628-6

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  • DOI: https://doi.org/10.1007/s11739-017-1628-6

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