Advertisement

Differences in prothrombotic response between the uninterrupted and interrupted apixaban therapies in patients undergoing cryoballoon ablation for paroxysmal atrial fibrillation: a randomized controlled study

  • Monami Ando
  • Yasuya IndenEmail author
  • Yukihiko Yoshida
  • Akinori Sairaku
  • Satoshi Yanagisawa
  • Hirohiko Suzuki
  • Ryo Watanabe
  • Masaki Takenaka
  • Mayuho Maeda
  • Toyoaki Murohara
Original Article
  • 215 Downloads

Abstract

Periprocedural bleeding and thromboembolic events are worrisome complications of catheter ablation for atrial fibrillation (AF). Periprocedural anticoagulation management could decrease the risk of these complications. However, evaluation of the complications from pulmonary vein isolation using cryoballoon related to different anticoagulation strategies is limited. Therefore, we aimed to compare prothrombotic responses as assessed on the basis of d-dimer levels between the uninterrupted and interrupted apixaban therapies during cryoballoon ablation. Ninety-seven consecutive patients with paroxysmal AF scheduled to undergo cryoballoon ablation were randomly assigned in a 1:2 ratio to uninterrupted apixaban therapy (Group 1, n = 32) or interrupted apixaban therapy (Group 2, n = 65). d-Dimer levels were measured immediately before the ablation, at the end of the ablation, and 24 and 48 h after the procedure. No statistical difference was observed in the baseline characteristics between the two groups. The rates of hemorrhagic complications were similar in both groups (major bleeding: 3.1 vs. 1.5%; p = 0.61, and minor bleeding: 3.1 vs. 4.6%; p = 0.73, respectively). No thromboembolic events occurred in either group. However, d-dimer levels 48 h after the ablation increased more markedly following the procedure in Group 2 than in Group 1 (from 0.58 ± 0.16 to 1.01 ± 0.42 μg/mL vs. 0.58 ± 0.20 to 0.82 ± 0.25 μg/mL; p = 0.01). In conclusion, uninterrupted apixaban therapy during the periprocedural period of cryoballoon ablation for AF did not increase the risk of bleeding in this study and might reduce the periprocedural risk of subclinical hypercoagulable state.

Keywords

Cryoballoon ablation Atrial fibrillation Apixaban Uninterrupted d-Dimer 

Notes

Compliance with ethical standards

Conflict of interest

None declared.

References

  1. 1.
    Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Métayer P, Clémenty J (1998) Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 339:659–666CrossRefGoogle Scholar
  2. 2.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castellá M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Alexandru Popescu B, Schotten U, Van Putte B, Vardas P (2016) ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: the Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO). Eur Heart J 37:2893–2962CrossRefGoogle Scholar
  3. 3.
    Metzner A, Reissmann B, Rausch P, Mathew S, Wohlmuth P, Tilz R, Rillig A, Lemes C, Deiss S, Heeger C, Kamioka M, Lin T, Ouyang F, Kuck KH, Wissner E (2014) One-year clinical outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon. Circ Arrhythm Electrophysiol 7:288–292CrossRefGoogle Scholar
  4. 4.
    Kuck KH, Brugada J, Fürnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C, Investigators FIREANDICE (2016) Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 374:2235–2245CrossRefGoogle Scholar
  5. 5.
    Okumura K, Matsumoto K, Kobayashi Y, Nogami A, Hokanson RB, Kueffer F (2016) Safety and efficacy of cryoballoon Ablation for paroxysmal atrial fibrillation in Japan—results from the Japanese prospective post-market surveillance study. Circ J 80:1744–1749CrossRefGoogle Scholar
  6. 6.
    Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146:857–867CrossRefGoogle Scholar
  7. 7.
    Di Biase L, Burkhardt JD, Santangeli P, Mohanty P, Sanchez JE, Horton R, Gallinghouse GJ, Themistoclakis S, Rossillo A, Lakkireddy D, Reddy M, Hao S, Hongo R, Beheiry S, Zagrodzky J, Rong B, Mohanty S, Elayi CS, Forleo G, Pelargonio G, Narducci ML, Dello Russo A, Casella M, Fassini G, Tondo C, Schweikert RA, Natale A (2014) Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation 129:2638–2644CrossRefGoogle Scholar
  8. 8.
    Cappato R, Marchlinski FE, Hohnloser SH, Naccarelli GV, Xiang J, Wilber DJ, Ma CS, Hess S, Wells DS, Juang G, Vijgen J, Hügl BJ, Balasubramaniam R, De Chillou C, Davies DW, Fields LE, Natale A, Investigators VENTURE-AF (2015) Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 36:1805–1811CrossRefGoogle Scholar
  9. 9.
    Di Biase L, Lakkireddy D, Trivedi C, Deneke T, Martinek M, Mohanty S, Mohanty P, Prakash S, Bai R, Reddy M, Gianni C, Horton R, Bailey S, Sigmund E, Derndorfer M, Schade A, Mueller P, Szoelloes A, Sanchez J, Al-Ahmad A, Hranitzky P, Gallinghouse GJ, Hongo RH, Beheiry S, Pürerfellner H, Burkhardt JD, Natale A (2015) Feasibility and safety of uninterrupted periprocedural apixaban administration in patients undergoing radiofrequency catheter ablation for atrial fibrillation: results from a multicenter study. Heart Rhythm 12:1162–1168CrossRefGoogle Scholar
  10. 10.
    Calkins H, Willems S, Gerstenfeld EP, Verma A, Schilling R, Hohnloser SH, Okumura K, Serota H, Nordaby M, Guiver K, Biss B, Brouwer MA, Grimaldi M, Investigators RE-CIRCUIT (2017) Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation. N Engl J Med 376:1627–1636CrossRefGoogle Scholar
  11. 11.
    Kirchhof P, Haeusler KG, Blank B, De Bono J, Callans D, Elvan A, Fetsch T, Van Gelder IC, Gentlesk P, Grimaldi M, Hansen J, Hindricks G, Al-Khalidi HR, Massaro T, Mont L, Nielsen JC, Nölker G, Piccini JP, De Potter T, Scherr D, Schotten U, Themistoclakis S, Todd D, Vijgen J, Di Biase L (2018) Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation. Eur Heart J 39:2942–2955CrossRefGoogle Scholar
  12. 12.
    Reynolds MR, Allison JS, Natale A, Weisberg IL, Ellenbogen KA, Richards M, Hsieh WH, Sutherland J, Cannon CP (2018) A prospective randomized trial of apixaban dosing during atrial fibrillation ablation: the AEIOU trial. JACC Clin Electrophysiol 4:580–588CrossRefGoogle Scholar
  13. 13.
    Nagao T, Inden Y, Shimano M, Fujita M, Yanagisawa S, Kato H, Ishikawa S, Miyoshi A, Okumura S, Ohguchi S, Yamamoto T, Yoshida N, Hirai M, Murohara T (2015) Efficacy and safety of apixaban in the patients undergoing the ablation of atrial fibrillation. Pacing Clin Electrophysiol 38:155–163CrossRefGoogle Scholar
  14. 14.
    Nagao T, Inden Y, Shimano M, Fujita M, Yanagisawa S, Kato H, Ishikawa S, Miyoshi A, Okumura S, Ohguchi S, Yamamoto T, Yoshida N, Hirai M, Murohara T (2015) Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing ablation for atrial fibrillation. Intern Med 54:1167–1173CrossRefGoogle Scholar
  15. 15.
    Kojima T, Fujiu K, Fukuma N, Matsunaga H, Oshima T, Matsuda J, Matsubara T, Shimizu Y, Oguri G, Hasumi E, Morita H, Komuro I (2018) Periprocedural complications in patients undergoing catheter ablation of atrial fibrillation without discontinuation of a vitamin K antagonist and direct oral anticoagulants. Circ J 82:1552–1557CrossRefGoogle Scholar
  16. 16.
    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, ARISTOTLE Committees and Investigators (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992CrossRefGoogle Scholar
  17. 17.
    Ogawa S, Shinohara Y, Kanmuri K (2011) Safety and efficacy of the oral direct factor Xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation—the ARISTOTLE-J study. Circ J 75:1852–1859CrossRefGoogle Scholar
  18. 18.
    Saenger AK, Christenson RH (2010) Stroke biomarkers: progress and challenges for diagnosis, prognosis, differentiation, and treatment. Clin Chem 56:21–33CrossRefGoogle Scholar
  19. 19.
    Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ (2006) d-Dimer predicts early clinical progression in ischemic stroke: confirmation using routine clinical assays. Stroke 37:1113–1115CrossRefGoogle Scholar
  20. 20.
    Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC, BRAIN Study Group (2009) Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke 40:77–85CrossRefGoogle Scholar
  21. 21.
    JCS Joint Working Group (2013) Guidelines for non-pharmacotherapy of cardiac arrhythmias (JCS 2011)—digest version. Circ J 77:249–274CrossRefGoogle Scholar
  22. 22.
    Harada M, Koshikawa M, Motoike Y, Ichikawa T, Sugimoto K, Watanabe E, Ozaki Y (2018) Left atrial appendage thrombus prior to atrial fibrillation ablation in the era of direct oral anticoagulants. Circ J 82:2715–2721CrossRefGoogle Scholar
  23. 23.
    Su W, Kowal R, Kowalski M, Metzner A, Svinarich JT, Wheelan K, Wang P (2015) Best practice guide for cryoballoon ablation in atrial fibrillation: the compilation experience of more than 3000 procedures. Heart Rhythm 12:1658–1666CrossRefGoogle Scholar
  24. 24.
    Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694CrossRefGoogle Scholar
  25. 25.
    Nin T, Sairaku A, Yoshida Y, Kamiya H, Tatematsu Y, Nanasato M, Inden Y, Hirayama H, Murohara T (2013) A randomized controlled trial of dabigatran versus warfarin for periablation anticoagulation in patients undergoing ablation of atrial fibrillation. Pacing Clin Electrophysiol 36:172–179CrossRefGoogle Scholar
  26. 26.
    Sairaku A, Yoshida Y, Ando M, Hirayama H, Nakano Y, Kihara Y (2013) A head-to-head comparison of periprocedural coagulability under anticoagulation with rivaroxaban versus dabigatran in patients undergoing ablation of atrial fibrillation. Clin Drug Investing 33:847–853CrossRefGoogle Scholar
  27. 27.
    Aryal MR, Ukaigwe A, Pandit A, Karmacharya P, Pradhan R, Mainali NR, Pathak R, Jalota L, Bhandari Y, Donato A (2014) Meta-analysis of efficacy and safety of rivaroxaban compared with warfarin or dabigatran in patients undergoing catheter ablation for atrial fibrillation. Am J Cardiol 114:577–582CrossRefGoogle Scholar
  28. 28.
    Providência R, Albenque JP, Combes S, Bouzeman A, Casteigt B, Combes N, Narayanan K, Marijon E, Boveda S (2014) Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter ablation of atrial fibrillation: a systematic review and meta-analysis. Heart 100:324–335CrossRefGoogle Scholar
  29. 29.
    Nagao T, Inden Y, Yanagisawa S, Kato H, Ishikawa S, Okumura S, Mizutani Y, Ito T, Yamamoto T, Yoshida N, Hirai M, Murohara T (2015) Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation. Heart Rhythm 12:1972–1978CrossRefGoogle Scholar
  30. 30.
    Khairy P, Chauvet P, Lehmann J, Lambert J, Macle L, Tanguay JF, Sirois MG, Santoianni D, Dubuc M (2003) Lower incidence of thrombus formation with cryoenergy versus radiofrequency catheter ablation. Circulation 107:2045–2050CrossRefGoogle Scholar
  31. 31.
    Okishige K, Nakamura T, Aoyagi H, Kawaguchi N, Yamashita M, Kurabayashi M, Suzuki H, Asano M, Shimura T, Yamauchi Y, Sasano T, Hirao K (2017) Comparative study of hemorrhagic and ischemic complications among anticoagulants in patients undergoing cryoballoon ablation for atrial fibrillation. J Cardiol 69:11–15CrossRefGoogle Scholar
  32. 32.
    Miyazaki S, Kajiyama T, Yamao K, Hada M, Yamaguchi M, Nakamura H, Hachiya H, Tada H, Hirao K, Iesaka Y (2019) Silent cerebral events/lesions after second-generation cryoballoon ablation: how can we reduce the risk of silent strokes? Heart Rhythm 16:41–48CrossRefGoogle Scholar
  33. 33.
    Kalantarian S, Stern TA, Mansour M, Ruskin JN (2013) Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann Intern Med 158:338–346CrossRefGoogle Scholar
  34. 34.
    Forleo GB, Della Rocca DG, Lavalle C, Mantica M, Papavasileiou LP, Ribatti V, Panattoni G, Santini L, Natale A, Biase LD (2016) A patient with asymptomatic cerebral lesions during AF ablation: how much should we worry? J Atr Fibrillation 8:1323Google Scholar
  35. 35.
    Ihara M, Washida K (2018) Linking atrial fibrillation with Alzheimer’s disease: epidemiological, pathological, and mechanistic evidence. J Alzheimers Dis 62:61–72CrossRefGoogle Scholar
  36. 36.
    Sadanaga T, Sadanaga M, Ogawa S (2010) Evidence that d-dimer levels predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy. J Am Coll Cardiol 55:2225–2231CrossRefGoogle Scholar
  37. 37.
    Vene N, Mavri A, Kosmelj K, Stegnar M (2003) High d-dimer levels predict cardiovascular events in patients with chronic atrial fibrillation during oral anticoagulant therapy. Thromb Haemost 90:1163–1172CrossRefGoogle Scholar
  38. 38.
    Hijazi Z, Oldgren J, Siegbahn A, Granger CB, Wallentin L (2013) Biomarkers in atrial fibrillation: a clinical review. Eur Heart J 34:1475–1480CrossRefGoogle Scholar
  39. 39.
    Granger CB, Miller JM, Bovill EG, Gruber A, Tracy RP, Krucoff MW, Green C, Berrios E, Harrington RA, Ohman EM, Califf RM (1995) Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation 91:1929–1935CrossRefGoogle Scholar
  40. 40.
    Genewein U, Haeberli A, Straub PW, Beer JH (1996) Rebound after cessation of oral anticoagulant therapy: the biochemical evidence. Br J Haematol 92:479–485CrossRefGoogle Scholar
  41. 41.
    Hermans C, Claeys D (2006) Review of the rebound phenomenon in new anticoagulant treatments. Curr Med Res Opin 22:471–481CrossRefGoogle Scholar
  42. 42.
    Hoke M, Koppensteiner R, Schillinger M, Haumer M, Minar E, Wiesbauer F, Huber CD, Mlekusch W (2010) d-Dimer testing in the diagnosis of transfemoral pseudoaneurysm after percutaneous transluminal procedures. J Vasc Surg 52:383–387CrossRefGoogle Scholar
  43. 43.
    Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA (2015) Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 373:2413–2424CrossRefGoogle Scholar
  44. 44.
    Brendel LC, Dobler F, Hessling G, Michel J, Braun SL, Steinsiek AL, Groha P, Eckl R, Deisenhofer I, Hyseni A, Roest M, Ott I, Steppich B (2017) The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban. J Interv Card Electrophysiol 49:237–244CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Monami Ando
    • 1
    • 2
  • Yasuya Inden
    • 2
    Email author
  • Yukihiko Yoshida
    • 1
  • Akinori Sairaku
    • 3
  • Satoshi Yanagisawa
    • 2
  • Hirohiko Suzuki
    • 1
  • Ryo Watanabe
    • 1
  • Masaki Takenaka
    • 1
  • Mayuho Maeda
    • 1
  • Toyoaki Murohara
    • 2
  1. 1.Department of Cardiology, Cardiovascular CenterNagoya Daini Red Cross HospitalNagoyaJapan
  2. 2.Department of CardiologyNagoya University Graduate School of MedicineNagoyaJapan
  3. 3.Department of CardiologyOnomichi General HospitalHiroshimaJapan

Personalised recommendations