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Journal of Thrombosis and Thrombolysis

, Volume 44, Issue 2, pp 169–178 | Cite as

Effectiveness and safety of apixaban therapy in daily-care patients with atrial fibrillation: results from the Dresden NOAC Registry

  • Sindy Helmert
  • Sandra Marten
  • Heike Mizera
  • Antje Reitter
  • Kurtulus Sahin
  • Luise Tittl
  • Jan Beyer-WestendorfEmail author
Article

Abstract

The effectiveness and safety of apixaban for stroke prevention in atrial fibrillation (SPAF) demonstrated in ARISTOTLE needs to be confirmed in daily care. To evaluate effectiveness and safety of apixaban therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 3000 patients on novel oral anticoagulants in daily care. Between 1 December 2012 and 31 August 2015, 514 patients receiving apixaban were enrolled. During a mean follow-up of 803.5 ± 228.9 days, the combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.4/100 patient-years in the intention-to-treat analysis (95% confidence interval [CI] 1.5–3.5) and at 1.8/100 patient-years (95% CI 1.0–2.8) in the on-treatment analysis (events within 3 days after last intake). On-treatment rates were numerically lower for patients selected for 5 mg apixaban (n = 404) twice daily [BID] compared with the 110 patients selected for 2.5 mg BID [1.6 (95% CI 0.8 to 2.7) vs. 2.6/100 patient-years (95% CI 0.8–6.1)]. On treatment, major bleeding occurred at a rate of 2.8/100 patient-years and significantly more often in patients receiving the 2.5 mg BID dose compared with the 5 mg BID dose (5.3 vs. 2.2/100 patient-years). Apixaban treatment discontinuation occurred in a total of 122 patients during follow-up (12.5/100 patient-years in Kaplan–Meier analysis). Our data contribute to the confirmation of effectiveness and relative safety of apixaban in daily-care patients. Furthermore, apixaban discontinuation rates were considerably lower than those reported for vitamin K antagonists.

Keywords

Anticoagulation Atrial fibrillation Bleeding Persistence Apixaban 

Notes

Acknowledgements

We are grateful to all participating patients and physicians, who continue to provide detailed information and documentation on the patients’ clinical course.

Funding

The sponsor of the Dresden NOAC Registry is the Gesellschaft für Technologie- und Wissenstransfer der Technischen Universität Dresden (GWT-TUD GmbH), Germany. The registry is supported by grants from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer. All authors declare that these companies and institutions had no influence on the study design, conduct of the study, data collection, statistical analysis, or preparation of the manuscript. All statistical analyses were performed by ClinStat GmbH, Institute for Clinical Research and Statistics, Max-Planck-Str. 22a; D-50858 Cologne, Germany.

Compliance with ethical standards

Conflict of interest

J.B.-W.: honoraria and research support from Bayer, Boehringer Ingelheim, Daiichi Sanyko. Pfizer and Portola S.M.: honoraria from Bayer. All other authors has no conflict of interest to declare.

Ethical approval

The study protocol of the Dresden NOAC Registry was approved by the local ethics committee at the Technical University Dresden (AZ EK 349092011) and registered at ClinicalTrials.gov (NCT01588119). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962CrossRefPubMedGoogle Scholar
  2. 2.
    Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15(5):625–651CrossRefPubMedGoogle Scholar
  3. 3.
    Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, Committees A, Investigators (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992. doi: 10.1056/NEJMoa1107039 CrossRefPubMedGoogle Scholar
  4. 4.
    Beyer-Westendorf J, Ebertz F, Forster K, Gelbricht V, Michalski F, Kohler C, Werth S, Endig H, Pannach S, Tittl L, Sahin K, Daschkow K, Weiss N (2015) Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 113(6):1247–1257CrossRefPubMedGoogle Scholar
  5. 5.
    Hecker J, Marten S, Keller L, Helmert S, Michalski F, Werth S, Sahin K, Tittl L, Beyer-Westendorf J (2016) Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 115(5):939–949CrossRefPubMedGoogle Scholar
  6. 6.
    Schulman S, Kearon C (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692–694CrossRefPubMedGoogle Scholar
  7. 7.
    SmPC apixaban (2015) http://www.medicines.org.uk/emc/medicine/24988. Accessed 06 January 2016
  8. 8.
    Lip GY, Keshishian A, Kamble S, Pan X, Mardekian J, Horblyuk R, Hamilton M (2016) Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin. A propensity score matched analysis. Thromb Haemost 116(5):975–986CrossRefPubMedGoogle Scholar
  9. 9.
    Larsen TB, Skjoth F, Nielsen PB, Kjaeldgaard JN, Lip GY (2016) Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 353:i3189CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Staerk L, Fosbol EL, Lip GYH, Lamberts M, Bonde AN, Torp-Pedersen C, Ozenne B, Gerds TA, Gislason GH, Olesen JB (2017) Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J 38(12):907–915PubMedGoogle Scholar
  11. 11.
    Sorensen R, Gislason G, Torp-Pedersen C, Olesen JB, Fosbol EL, Hvidtfeldt MW, Karasoy D, Lamberts M, Charlot M, Kober L, Weeke P, Lip GY, Hansen ML (2013) Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. BMJ Open 3(5):e002758CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Camm AJ, Amarenco P, Haas S, Hess S, Kirchhof P, Kuhls S, van Eickels M, Turpie AG (2016) XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 37(14):1145–1153. doi: 10.1093/eurheartj/ehv466 CrossRefPubMedGoogle Scholar
  13. 13.
    Abraham NS, Singh S, Alexander GC, Heien H, Haas LR, Crown W, Shah ND (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:h1857CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Villines TC, Schnee J, Fraeman K, Siu K, Reynolds MW, Collins J, Schwartzman E (2015) A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system. Thromb Haemost 114(6):1290–1298CrossRefPubMedGoogle Scholar
  15. 15.
    Avgil-Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Behlouli H, Pilote L (2016) Dabigatran use in elderly patients with atrial fibrillation. Thromb Haemost 115(1):152–160CrossRefPubMedGoogle Scholar
  16. 16.
    Nielsen PB, Skjoth F, Sogaard M, Kjaeldgaard JN, Lip GY, Larsen TB (2017) Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 356:j510CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Konigsbrugge O, Simon A, Domanovits H, Pabinger I, Ay C (2016) Thromboembolic events, bleeding, and drug discontinuation in patients with atrial fibrillation on anticoagulation: a prospective hospital-based registry. BMC Cardiovasc Disord 16(1):254CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Halvorsen S, Ghanima W, Fride Tvete I, Hoxmark C, Falck P, Solli O, Jonasson C (2017) A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants. Eur Heart J Cardiovasc Pharmacother 3(1):28–36CrossRefPubMedGoogle Scholar
  19. 19.
    Fay MR, Martins JL, Czekay B (2016) Oral anticoagulant prescribing patterns for stroke prevention in atrial fibrillation among general practitioners and cardiologists in three European countries. Eur Heart J 37:510 (Abstract P2597)CrossRefGoogle Scholar
  20. 20.
    Nguyen E, White CM, Patel MR, Fields LE, Peacock WF, Crivera C, Coleman CI (2016) Doses of apixaban and rivaroxaban prescribed in real-world United States cardiology practices compared to registration trials. Curr Med Res Opin 32(7):1277–1279CrossRefPubMedGoogle Scholar
  21. 21.
    Yao X, Shah ND, Sangaralingham LR, Gersh BJ (2016) Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants in patients without severe renal impairment. Elsevier, Amsterdam. doi: 10.1016/j.jval.2016.03.027. Accessed 04 October 2016Google Scholar
  22. 22.
    Michalski F, Tittl L, Werth S, Hansel U, Pannach S, Sahin K, Weiss N, Beyer-Westendorf J (2015) Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants. Results from the Dresden NOAC registry. Thromb Haemost 114(5):1076–1084. doi: 10.1160/th15-02-0116 CrossRefPubMedGoogle Scholar
  23. 23.
    Beyer-Westendorf J, Ehlken B, Evers T (2016) Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation. Europace 18(8):1150–1157CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sindy Helmert
    • 1
  • Sandra Marten
    • 1
  • Heike Mizera
    • 1
  • Antje Reitter
    • 1
  • Kurtulus Sahin
    • 2
  • Luise Tittl
    • 1
  • Jan Beyer-Westendorf
    • 1
    • 3
    Email author
  1. 1.Thrombosis Research Unit, Division Hematology, Department of Medicine IUniversity Hospital “Carl Gustav Carus” DresdenDresdenGermany
  2. 2.ClinStat GmbHInstitute for Clinical Research and StatisticsCologneGermany
  3. 3.Kings Thrombosis Service, Department of HematologyKings College LondonLondonUK

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