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Rationale and Design of the Evaluation of Oral Anticoagulation for Reduction of Thrombo-embolism in Chinese Patients with Device-Detected Subclinical Atrial Fibrillation (ART-CAF) Trial: an Open-Label Registry-Based Clinical Trial

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Abstract

Purpose

Subclinical atrial fibrillation (AF) was found in a large number of pacemaker patients. It is not certain whether there is a similar risk/benefit ratio for oral anticoagulation in patients with subclinical AF compared to patients with similar risk profiles and clinically diagnosed AF. Given the weakness of clinical evidence for oral anticoagulation in patients with device-detected subclinical AF, specific recommendations in most guidelines for this population are scarce and rarely similar.

Methods

ART-CAF trial was primarily designed to evaluate the efficacy and safety of oral anticoagulant agent use in patients with device-detected subclinical AF at the approved dosage to prevent stroke and systemic arterial embolism. It is an open-label, registry-based, prospective, multicenter, cohort study, recruiting patients with subclinical AF first detected by a pacemaker, implantable cardioverter-defibrillator, or insertable cardiac monitor after device implantation for more than 3 months. The primary outcome is a composite of ischemic stroke and systemic arterial embolism. The primary safety outcome is the occurrence of clinically overt major bleeding. Approximately 750 patients will be needed to be enrolled to the two treatment groups in a 1:1 ratio until 66 primary efficacy outcomes are observed. The anticipated follow-up period is approximately 70 months from the enrollment of the first patient.

Conclusions

ART-CAF evaluates the feasibility of selecting high-risk patients suitable for anticoagulation by AF burden combined with CHA2DS2-VASc score after pacemaker implantation and aims to select patients who could benefit from anticoagulation.

Trial Registration

http://www.chictr.org.cn/index.aspx ChiCTR1800016221

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References

  1. Nielsen JC. Mortality and incidence of atrial fibrillation in paced patients. J Cardiovasc Electrophysiol. 2002;13(1 Suppl):S17–22.

    Article  PubMed  Google Scholar 

  2. Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Hilker C, et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol. 2009;2(5):474–80.

    Article  PubMed  Google Scholar 

  3. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R, et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the atrial diagnostics ancillary study of the MOde selection trial (MOST). Circulation. 2003;107(12):1614–9.

    Article  PubMed  Google Scholar 

  4. Healey JS, Connolly SJ, Gold MR, Israel CW, van Gelder I, Capucci A, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120–9.

    Article  PubMed  CAS  Google Scholar 

  5. Shanmugam N, Boerdlein A, Proff J, Ong P, Valencia O, Maier SKG, et al. Detection of atrial high-rate events by continuous home monitoring: clinical significance in the heart failure-cardiac resynchronization therapy population. Europace. 2012;14(2):230–7.

    Article  PubMed  Google Scholar 

  6. Cheung JW, Keating RJ, Stein KM, et al. Newly detected atrial fibrillation following dual chamber pacemaker implantation. J Cardiovasc Electrophysiol. 2006;17(12):1323–8.

    Article  PubMed  Google Scholar 

  7. Orlov MV, Ghali JK, Araghi-Niknam M, et al. Asymptomatic atrial fibrillation in pacemaker recipients: incidence, progression, and determinants based on the atrial high rate trial. Pacing Clin Electrophysiol. 2007;30(3):404–11.

    Article  PubMed  Google Scholar 

  8. Defaye P, Dournaux F, Mouton E. Prevalence of supraventricular arrhythmias from the automated analysis of data stored in the DDD pacemakers of 617 patients: the AIDA study. The AIDA multicenter study group. Automatic interpretation for diagnosis assistance. Pacing Clin Electrophysiol. 1998;21(1 Pt 2):250–5.

    Article  PubMed  CAS  Google Scholar 

  9. Al-Khatib SM, Thomas L, Wallentin L, et al. Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial. Eur Heart J. 2013;34(31):2464–71.

    Article  PubMed  CAS  Google Scholar 

  10. Steinberg BA, Hellkamp AS, Lokhnygina Y, Patel MR, Breithardt G, Hankey GJ, et al. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF trial. Eur Heart J. 2015;36(5):288–96.

    Article  PubMed  Google Scholar 

  11. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of atrial fibrillation. JAMA. 2001;285(22):2864–70.

    Article  PubMed  CAS  Google Scholar 

  12. Lip GY, Frison L, Halperin JL, et al. Identifying patients at high risk for stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. Stroke. 2010;41(12):2731–8.

    Article  PubMed  CAS  Google Scholar 

  13. Hohnloser SH, Capucci A, Fain E, et al. ASymptomatic atrial fibrillation and stroke evaluation in pacemaker patients and the atrial fibrillation reduction atrial pacing trial (ASSERT). Am Heart J. 2006;152(3):442–7.

    Article  PubMed  Google Scholar 

  14. Capucci A, Santini M, Padeletti L, Gulizia M, Botto G, Boriani G, et al. Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. J Am Coll Cardiol. 2005;46(10):1913–20.

    Article  PubMed  Google Scholar 

  15. Boriani G, Botto GL, Padeletti L, Santini M, Capucci A, Gulizia M, et al. Improving stroke risk stratification using the CHADS2 and CHA2DS2-VASc risk scores in patients with paroxysmal atrial fibrillation by continuous arrhythmia burden monitoring. Stroke. 2011;42(6):1768–70.

    Article  PubMed  Google Scholar 

  16. Botto GL, Padeletti L, Santini M, et al. Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events. J Cardiovasc Electrophysiol. 2009;20(3):241–8.

    Article  PubMed  Google Scholar 

  17. Boriani G, Glotzer TV, Santini M, West TM, de Melis M, Sepsi M, et al. Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (stroke preventiOn strategies based on atrial fibrillation information from implanted devices). Eur Heart J. 2014;35(8):508–16.

    Article  PubMed  Google Scholar 

  18. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1–e76.

    Article  PubMed  Google Scholar 

  19. Lopes RD, Alings M, Connolly SJ, Beresh H, Granger CB, Mazuecos JB, et al. Rationale and design of the Apixaban for the reduction of Thrombo-embolism in patients with device-detected sub-clinical atrial fibrillation (ARTESiA) trial. Am Heart J. 2017;189:137–45.

    Article  PubMed  Google Scholar 

  20. Kirchhof P, Blank BF, Calvert M, Camm AJ, Chlouverakis G, Diener HC, et al. Probing oral anticoagulation in patients with atrial high rate episodes: rationale and design of the non-vitamin K antagonist oral anticoagulants in patients with atrial high rate episodes (NOAH-AFNET 6) trial. Am Heart J. 2017;190:12–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Kaufman ES, Israel CW, Nair GM, Armaganijan L, Divakaramenon S, Mairesse GH, et al. Positive predictive value of device-detected atrial high-rate episodes at different rates and durations: an analysis from ASSERT. Heart Rhythm. 2012;9(8):1241–6.

    Article  PubMed  Google Scholar 

  22. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012;33(20):2551–67.

    Article  PubMed  Google Scholar 

  23. Hicks KA, Tcheng JE, Bozkurt B, et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association task force on clinical data standards (writing committee to develop cardiovascular endpoints data standards). Circulation. 2015;132(4):302–61.

    Article  PubMed  Google Scholar 

  24. Pollak WM, Simmons JD, Interian A, et al. Clinical utility of intraatrial pacemaker stored electrograms to diagnose atrial fibrillation and flutter. Pacing Clin Electrophysiol. 2001;24(4 Pt 1):424–9.

    Article  PubMed  CAS  Google Scholar 

  25. Purerfellner H, Gillis AM, Holbrook R, et al. Accuracy of atrial tachyarrhythmia detection in implantable devices with arrhythmia therapies. Pacing Clin Electrophysiol. 2004;27(7):983–92.

    Article  PubMed  Google Scholar 

  26. Chao TF, Liu CJ, Wang KL, Lin YJ, Chang SL, Lo LW, et al. Should atrial fibrillation patients with 1 additional risk factor of the CHA2DS2-VASc score (beyond sex) receive oral anticoagulation. J Am Coll Cardiol. 2015;65(7):635–42.

    Article  PubMed  Google Scholar 

  27. Daoud EG, Glotzer TV, Wyse DG, Ezekowitz MD, Hilker C, Koehler J, et al. Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. Heart Rhythm. 2011;8(9):1416–23.

    Article  PubMed  Google Scholar 

  28. Brambatti M, Connolly SJ, Gold MR, Morillo CA, Capucci A, Muto C, et al. Temporal relationship between subclinical atrial fibrillation and embolic events. Circulation. 2014;129(21):2094–9.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 Qingchun East Road, Hangzhou, 310016, Zhejiang, China

    Ying Yang, Fen Xu, Jinshan Tong, Xia Sheng, Yiwen Pan, Jiangfen Jiang, Jiefang Zhang, Dongmei Jiang, Linlin Zhao & Guosheng Fu

  2. Deqing County PPL Hospital, Huzhou, Zhejiang, China

    Leyan Cai

  3. Department of Cardiology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, China

    Wenbing Jiang

Authors
  1. Ying Yang
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  2. Fen Xu
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  3. Jinshan Tong
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  4. Leyan Cai
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  5. Wenbing Jiang
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  6. Xia Sheng
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  7. Yiwen Pan
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  8. Jiangfen Jiang
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  9. Jiefang Zhang
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  10. Dongmei Jiang
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  11. Linlin Zhao
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  12. Guosheng Fu
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Corresponding authors

Correspondence to Ying Yang or Guosheng Fu.

Ethics declarations

Ethics

The study was approved by the medical ethics committees of Sir Run Run Shaw Hospital, affiliated to Medical School of Zhejiang University, in February 2018 (Keyan20180206-10). This trial will be conducted in compliance with the study protocol, good clinical practices, principles laid down in the Declaration of Helsinki, and applicable local regulations.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This study is conducted in accordance with the Declaration of Helsinki and has been approved by the medical ethics committees of Sir Run Run Shaw Hospital, affiliated to Medical School of Zhejiang University, in February 2018 (Ethics approval number: Keyan20180206-10).

Informed Consent

Written informed consent was obtained from all patients or their legally authorized representatives included in the study before randomization.

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Yang, Y., Xu, F., Tong, J. et al. Rationale and Design of the Evaluation of Oral Anticoagulation for Reduction of Thrombo-embolism in Chinese Patients with Device-Detected Subclinical Atrial Fibrillation (ART-CAF) Trial: an Open-Label Registry-Based Clinical Trial. Cardiovasc Drugs Ther 32, 389–396 (2018). https://doi.org/10.1007/s10557-018-6807-9

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