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Rationale and design of VENTURE-AF: a randomized, open-label, active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects undergoing catheter ablation for atrial fibrillation

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the safety of uninterrupted rivaroxaban, a novel oral anticoagulant that directly inhibits factor Xa, and a vitamin K antagonist (VKA) in eligible adult patients with nonvalvular AF (NVAF) who are scheduled for a catheter ablation.

Methods/design

This is a prospective, randomized, open-label, active-controlled, global multicenter safety study of up to 250 randomized patients. Eligible patients with paroxysmal or persistent NVAF, a left ventricular ejection fraction >40 %, and a creatinine clearance >50 mL/min will be randomized 1:1 to rivaroxaban 20 mg orally once daily or to dose-adjusted oral VKA (recommended international normalized ratio (INR) 2.0–3.0) and stabilized on anticoagulation therapy for 1–7 days (if no intracardiac thrombus on transesophageal echocardiogram (TEE) immediately prerandomization/post-randomization or if 3 weeks of sufficient anticoagulation is documented) or for 4–5 weeks (if no TEE, no documented 3 weeks of sufficient anticoagulation, or by patient choice). During catheter ablation, heparin will be administered (ACT-targeted range = 300–400 s) after catheter ablation, and VKA will be managed per usual care. The next dose of rivaroxaban will be provided at least 6 h after establishment of hemostasis. The primary endpoint will be the incidence of post-procedure major bleeding events observed during the first 30 ± 5 days post-ablation. Secondary endpoints will include post-procedure thromboembolic events, additional bleeding, time-to-event, and medication adherence.

Relevance

This study is intended to provide information about the safety characteristics of rivaroxaban in patients with NVAF undergoing catheter ablation.

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Abbreviations

AF:

Atrial fibrillation

CEC:

Clinical Endpoint Committee

CNS:

Central nervous system

CrCl:

Creatinine clearance

DVT:

Deep vein thrombosis

FDA:

Food and Drug Administration

FXa:

Factor Xa

GUSTO:

Global Use of Strategies to Open Occluded Coronary Arteries

INR:

International normalized ratio

ISTH:

International Society on Thrombosis and Haemostasis

ITT:

Intention-to-treat

LMWH:

Low molecular weight heparin

NVAF:

Nonvalvular atrial fibrillation

PE:

Pulmonary embolism

PT:

Prothrombin time

PTT:

Partial thromboplastin time

TEE:

Transesophageal echocardiogram

TIA:

Transient ischemic attack

TIMI:

Thrombolysis in Myocardial Infarction

US:

United States

VKA:

Vitamin K antagonist

VTE:

Venous thromboembolism

References

  1. Dewire, J., & Calkins, H. (2013). Update on atrial fibrillation catheter ablation technologies and techniques. Nature Reviews Cardiology, 10(10), 599–612.

    Article  PubMed  Google Scholar 

  2. Wolf, P. A., Abbott, R. D., & Kannel, W. B. (1991). Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke, 22(8), 983–988.

    Article  PubMed  CAS  Google Scholar 

  3. Chinitz, J. S., Castellano, J. M., Kovacic, J. C., & Fuster, V. (2012). Atrial fibrillation, stroke, and quality of life. Annals of the New York Academy of Sciences, 1254, 140–150.

    Article  PubMed  CAS  Google Scholar 

  4. Ball, J., Carrington, M. J., McMurray, J. J., & Stewart, S. (2013). Atrial fibrillation: profile and burden of an evolving epidemic in the 21st century. International Journal of Cardiology, 167(5), 1807–1824.

    Article  PubMed  Google Scholar 

  5. Nguyen, T. N., Hilmer, S. N., & Cumming, R. G. (2013). Review of epidemiology and management of atrial fibrillation in developing countries. International Journal of Cardiology, 167(6), 2412–2420.

    Article  PubMed  Google Scholar 

  6. Callahan, T., & Baranowski, B. (2011). Managing newly diagnosed atrial fibrillation: rate, rhythm, and risk. Cleveland Clinic Journal of Medicine, 78(4), 258–264.

    Article  PubMed  Google Scholar 

  7. Zhang, Y. Y., Qiu, C., Davis, P. J., Jhaveri, M., Prystowsky, E. N., Kowey, P., et al. (2013). Predictors of progression of recently diagnosed atrial fibrillation in Registry on Cardiac Rhythm Disorders Assessing the Control of Atrial Fibrillation (RecordAF)-United States cohort. American Journal of Cardiology, 112(1), 79–84.

    Article  PubMed  Google Scholar 

  8. Camm, A. J., Lip, G. Y., De Caterina, R., Savelieva, I., Atar, D., Hohnloser, S. H., et al. (2010). 2012 focused update of the ESC. Developed with the special contribution of the European Heart Rhythm Association. Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. European Heart Journal, 33(21), 2719–2747. Erratum in (2013) European Heart Journal, 34(10), 790.

    Google Scholar 

  9. Diener, H. C., Weber, R., Lip, G. Y., & Hohnloser, S. H. (2012). Stroke prevention in atrial fibrillation: do we still need warfarin? Current Opinion in Neurology, 25(1), 27–35.

    Article  PubMed  CAS  Google Scholar 

  10. Kimmel, S. E., French, B., Anderson, J. L., Gage, B. F., Johnson, J. A., Rosenberg, Y. D., et al. (2013). Rationale and design of the clarification of optimal anticoagulation through genetics trial. American Heart Journal, 166(3), 435–441.

    Article  PubMed  Google Scholar 

  11. Patel, M. R., Mahaffey, K. W., Garg, J., Pan, G., Singer, D. E., Hacke, W., et al. (2011). Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New England Journal of Medicine, 365(10), 883–895.

    Article  PubMed  CAS  Google Scholar 

  12. Perzborn, E., Strassburger, J., Wilmen, A., Pohlmann, J., Roehrig, S., Schlemmer, K. H., et al. (2005). In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939—an oral, direct factor Xa inhibitor. Journal of Thrombosis and Haemostasis, 3(3), 514–521.

    Article  PubMed  CAS  Google Scholar 

  13. Ringwala, S. M., Dibattiste, P. M., & Schneider, D. J. (2012). Effects on platelet function of a direct acting antagonist of coagulation factor Xa. Journal of Thrombosis and Thrombolysis, 34(3), 291–296.

    Article  PubMed  CAS  Google Scholar 

  14. Deshmukh, A., Patel, N. J., Pant, S., et al. (2013). In-hospital complications associated with catheter ablation of atrial fibrillation in the United States between 2000 and 2010: analysis of 93 801 procedures. Circulation, 128(19), 2104–2112.

    Article  PubMed  Google Scholar 

  15. Cappato, R., Calkins, H., Chen, S. A., et al. (2010). Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation Arrhythmia Electrophysiology, 3(1), 32–38.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Members of the Steering Committee thank participating patients, VENTURE-AF Investigators, and their teams for patient identification, enrollment, care and reporting, past and present members of the VENTURE-AF Core Integrated Team at Johnson & Johnson and Bayer, and Johnson & Johnson and Bayer for sponsorship of this study. Thanks also to C. V. Damaraju, PhD for initial expert statistical support.

Conflict of interest

All authors received research grant support from the sponsors of the trial (Johnson & Johnson and Bayer). Gerald V. Naccarelli, MD, FACC, FHRS is a consultant for Glaxo-Smith-Kline, Pfizer, Xention, Sanofi, Bristol Myers Squibb, Merck, Biosense-Webster, Janssen, Otsuka, Daiichi-Sankyo, and Boehringer Ingelheim. Riccardo Cappato, MD, FESC: Biosense Webster, St Jude Medical, and Bard. StefanH. Hohnloser, MD, FACC, FESC, FHRS: consulting and lecture fees from Boehringer Ingelheim, BMS, Bayer, Pfizer, and Sanofi-aventis. Francis E. Marchlinski, MD, FACC: no further disclosures. David J. Wilber, MD, FAHA, FACC, FHRS: lectures and consulting fees from Biosense Webster, Medtronic, St Jude, Cardioinsight and research support from Biosense Webster, Medtronic. Changsheng Ma, MD, FHRS: no further disclosures. David Wyn Davies MD, FRCP, FHRS: consultant for Boston Scientific, Janssen, Medtronic and Rhythmia. Andrea Natale MD, FACC, FHRS, FESC: Biosense Webster, Boston Scientific, Janssen, St. Jude Medical, Medtronic and Biotronik. Larry E. Fields, MD, FAHA, FACC: is an employee of Johnson & Johnson at Janssen Scientific Affairs, LLC. Jim Xiang, PhD: is an employee of Johnson & Johnson at Janssen Research & Development, LLC. Susanne Hess, MD: is an employee of Bayer.

Author information

Authors and Affiliations

  1. Texas Cardiac Arrhythmia Institute, St. David’s Medical Center, 3000 N IH35, Suite 700, Austin, TX, 78705, USA

    Andrea Natale

  2. Heart and Vascular Institute, Penn State University College of Medicine, P. O. Box 850, MC H047, 500 University Drive, Room H1511, Hershey, PA, 17033, USA

    Gerald V. Naccarelli

  3. Arrhythmia and Electrophysiology Center, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy

    Riccardo Cappato

  4. Department of Cardiology, Division of Clinical Electrophysiology, J.W. Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany

    Stefan H. Hohnloser

  5. Department of Medicine, Section of Cardiac Electrophysiology, Cardiovascular Division, Hospital of University of Pennsylvania, 3400 Spruce Street, 9 Founders Pavilion, Philadelphia, PA, 19104, USA

    Francis E. Marchlinski

  6. Department of Medicine, Cardiovascular Institute, Loyola University Medical Center, 2160 S First Ave, Building 110, Room 6232, Maywood, IL, 60153, USA

    David J. Wilber

  7. Janssen Research and Development, LLC, 1000 RTE 202, Box 300, Raritan, NJ, 08869, USA

    Jim Xiang

  8. Cardiology Department, Atrial Fibrillation Center, Beijing An Zhen Hospital, Capital Medical University, An Ding Men Wai, An Zhen Li, Chao Yang District, Beijing, 100029, People’s Republic of China

    Changsheng Ma

  9. Global Medical Affairs Xarelto, Bayer HealthCare Pharmaceuticals, Bayer Center No. 27, Dong San Huan North Road, Chaoyang District, Beijing, 100020, People’s Republic of China

    Susanne Hess

  10. St. Mary’s Hospital, Imperial NHS Trust, 78 Harley Street, London, W1G 7HJ, UK

    David Wyn Davies

  11. Janssen Scientific Affairs, LLC, 1000 RTE 202, Box 300, Raritan, NJ, 08869, USA

    Larry E. Fields

Authors
  1. Gerald V. Naccarelli
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  2. Riccardo Cappato
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  3. Stefan H. Hohnloser
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  4. Francis E. Marchlinski
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  5. David J. Wilber
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  6. Jim Xiang
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  7. Changsheng Ma
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  8. Susanne Hess
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  9. David Wyn Davies
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  10. Larry E. Fields
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  11. Andrea Natale
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on behalf of the VENTURE-AF Investigators

Corresponding author

Correspondence to Andrea Natale.

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Naccarelli, G.V., Cappato, R., Hohnloser, S.H. et al. Rationale and design of VENTURE-AF: a randomized, open-label, active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects undergoing catheter ablation for atrial fibrillation. J Interv Card Electrophysiol 41, 107–116 (2014). https://doi.org/10.1007/s10840-014-9924-9

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  • DOI: https://doi.org/10.1007/s10840-014-9924-9

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