Download PDF
Thromb Haemost 2016; 115(05): 939-949
DOI: 10.1160/TH15-10-0840
Coagulation and Fibrinolysis
Schattauer GmbH

Effectiveness and safety of rivaroxaban therapy in daily-care patients with atrial fibrillation

Results from the Dresden NOAC Registry
Judith Hecker
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Sandra Marten
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Loretta Keller
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Sindy Helmert
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Franziska Michalski
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Sebastian Werth
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Kurtulus Sahin
2   ClinStat GmbH, Institute for Clinical Research and Statistics, Cologne, Germany
,
Luise Tittl
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Jan Beyer-Westendorf
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
› Author Affiliations Financial Support: The NOAC registry is supported by the Gesellschaft für Technologie- und Wissenstransfer der Technischen Universität Dresden (GWT-TUD GmbH), Germany (sponsor); by research funds of the University Hospital “Carl Gustav Carus”, Dresden, and by grants from Bayer HealthCare, Boehringer Ingelheim, 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.
Further Information

Publication History

Received: 30 October 2015

Accepted after major revision: 28 January 2015

Publication Date:
06 December 2017 (online)

    Permissions and Reprints

Summary

The effectiveness and safety of rivaroxaban for stroke prevention in atrial fibrillation (SPAF) demonstrated in ROCKET AF needs to be confirmed in daily care. To evaluate effectiveness and safety of rivaroxaban therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2700 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 1204 SPAF patients receiving rivaroxaban were enrolled. During a mean follow-up of 796.2 ± 207.3 days, the combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.03/100 patient-years in the intention-totreat analysis (95 % confidence interval [CI] 1.5–2.7) and at 1.7/100 patient-years in the on-treatment analysis (events within 3 days after last intake). On-treatment rates were higher in patients selected for 15 mg rivaroxaban (n=384) once daily [OD] compared with the 820 patients selected for 20 mg OD (2.7 [95 % CI 1.6–4.2] vs 1.25/100 patient-years [95 % CI 0.8–1.9]). On treatment, major bleeding occurred at a rate of 3.0/100 patient-years and significantly more often in patients receiving the 15 mg OD dose compared with the 20 mg OD dose (4.5 vs 2.4/100 patient-years). Rivaroxaban treatment discontinuation occurred in a total of 277 patients during follow-up (12.0/100 patientyears in Kaplan-Meier analysis). Our data contribute to the confirmation of effectiveness and relative safety of rivaroxaban in daily-care patients. Furthermore, rivaroxaban discontinuation rates were considerably lower than those reported for vitamin K antagonists.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Anticoagulation - atrial fibrillation - bleeding - persistence - rivaroxaban

 

  • References

  • 1 Camm AJ. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
    CrossrefPubMedGoogle Scholar
  • 2 Ageno W. et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest 2012; 141 (02) Suppl e44S-e88S.
    CrossrefPubMedGoogle Scholar
  • 3 van Walraven C. et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129: 1155-1166.
    CrossrefPubMedGoogle Scholar
  • 4 Snipelisky D, Kusumoto F. Current strategies to minimize the bleeding risk of warfarin. J Blood Med 2013; 4: 89-99.
    PubMedGoogle Scholar
  • 5 Heidbuchel H. et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013; 15: 625-651.
    CrossrefPubMedGoogle Scholar
  • 6 Patel MR. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
    CrossrefPubMedGoogle Scholar
  • 7 Piccini JP. et al. Management of major bleeding events in patients treated with rivaroxaban vs warfarin: results from the ROCKET AF trial. Eur Heart J. 2014 Epub ahead of print.
    PubMedGoogle Scholar
  • 8 Beyer-Westendorf J. et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J 2014; 35: 1888-1896.
    CrossrefPubMedGoogle Scholar
  • 9 Beyer-Westendorf J. et al. Safety of switching from Vitamin-K antagonists to dabigatran or rivaroxaban in daily care – results from the Dresden NOAC registry. Br J Clin Pharmacol. 2014 Epub ahead of print.
    PubMedGoogle Scholar
  • 10 Beyer-Westendorf J. et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-962.
    CrossrefPubMedGoogle Scholar
  • 11 Beyer-Westendorf J. et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 2015; 113: 1247-1257.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Michalski F. et al. 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 2015; 114: 1076-1084.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
    CrossrefPubMedGoogle Scholar
  • 14 Beyer-Westendorf J. et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace. 2015 Epub ahead of print.
    PubMedGoogle Scholar
  • 15 Graham DJ. et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation. Circulation. 2014 Epub ahead of print.
    PubMedGoogle Scholar
  • 16 Sorensen R. et al. Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. Br Med J Open 2013; 3.
    PubMedGoogle Scholar
  • 17 Laliberte F. et al. Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Curr Med Res Opin 2014; 30: 1317-1325.
    CrossrefPubMedGoogle Scholar
  • 18 Tamayo S. et al. Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol 2015; 38: 63-68.
    CrossrefPubMedGoogle Scholar
  • 19 Camm AJ. et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2015 Epub ahead of print.
    PubMedGoogle Scholar
  • 20 Seeger JD. et al. Safety and effectiveness of dabigatran and warfarin in routine care of patients with atrial fibrillation. Thromb Haemost 2015; 114: 1277-1289.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Abraham NS. et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. Br Med J 2015; 350: h1857.
    CrossrefPubMedGoogle Scholar
  • 22 Villines TC. et al. A comparison of the safety and effectiveness of dabigatran and warfarin in non-valvular atrial fibrillation patients in a large healthcare system. Thromb Haemost 2015; 114: 1290-1298.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Avgil-Tsadok M. et al. Dabigatran use in elderly patients with atrial fibrillation. Thromb Haemost. 2015: 115 Epub ahead of print.
    PubMedGoogle Scholar
  • 24 Maura G. et al. Comparison of the Short-Term Risk of Bleeding and Arterial Thromboembolic Events in Nonvalvular Atrial Fibrillation Patients Newly Treated With Dabigatran or Rivaroxaban versus Vitamin K Antagonists: A French Nationwide Propensity-Matched Cohort Study. Circulation. 2015 Epub ahead of print.
    PubMedGoogle Scholar
  • 25 Beyth RJ. et al. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
    CrossrefPubMedGoogle Scholar
  • 26 Gomes T. et al. Rates of hemorrhage during warfarin therapy for atrial fibrillation. Cmaj 2013; 185: E121-E127.
    CrossrefPubMedGoogle Scholar
  • 27 Willey VJ. et al. Management patterns and outcomes of patients with venous thromboembolism in the usual community practice setting. Clin Ther 2004; 26: 1149-1159.
    CrossrefPubMedGoogle Scholar
  • 28 Steffensen FH. et al. Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort. J Intern Med 1997; 242: 497-503.
    CrossrefPubMedGoogle Scholar
  • 29 Nelson WW. et al. Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation. Curr Med Res Opin 2014; 30: 2461-2469.
    CrossrefPubMedGoogle Scholar
  • 30 Nelson WW. et al. Medication Persistence and Discontinuation of Rivaroxaban and Dabigatran Etexilate among Patients with Non-Valvular Atrial Fibrillation. Curr Med Res Opin 2015; 1-31.
    PubMedGoogle Scholar
  • 31 Gallagher AM. et al. Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis?. J Thromb Haemost 2008; 6: 1500-1506.
    CrossrefPubMedGoogle Scholar
  • 32 Hylek EM. et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689-2696.
    CrossrefPubMedGoogle Scholar
  • 33 Fang MC. et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes 2010; 3: 624-631.
    CrossrefPubMedGoogle Scholar
  • 34 Lauffenburger JC. et al. Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation: a retrospective cohort study. J Am Heart Assoc. 2015 Epub ahead of print.
    PubMedGoogle Scholar
  • 35 Larsen TB. et al. Dabigatran and warfarin for secondary prevention of stroke in atrial fibrillation patients: a nationwide cohort study. Am J Med 2014; 127: 1172-1178 e5.
    CrossrefPubMedGoogle Scholar