Study of Modifications Induced by Continued Direct Oral Anticoagulant Therapy During Atrial Fibrillation Ablation Procedures on Standard Hemostasis Parameters

Overview

Journal J Clin Med

Specialty General Medicine

Date 2023 Mar 29

PMID 36983237

Authors

Marie Muller

Julien Godet

Xavier Delabranche

Laurent Sattler

David Millard

Halim Marzak

Paul Michel Mertes

Annick Steib

Lelia Grunebaum

Laurence Jesel

Charles Ambroise Tacquard

Affiliations

Soon will be listed here.

Abstract

Background: Unfractionated heparin (UFH) is used as an anticoagulant during the atrial fibrillation (AF) ablation procedure to prevent the occurrence of thromboembolic events. Guidelines recommend an activated clotting time (ACT) greater than 300 s (s) based on studies of patients treated with vitamin K antagonist (VKA) for their AF. However, direct oral anticoagulants (DOACs) have supplanted VKAs in AF and are now used as first-line therapy. It is recommended not to interrupt them during the procedure, which could interfere with the ACT measures.

Objective: To assess the real-life relationship between ACT, DOAC concentrations, and UFH anti-Xa activity in patients treated by uninterrupted DOAC therapy.

Methods: We conducted a single-center retrospective study. We analyzed consecutive patients with AF who underwent catheter ablation under DOAC therapy.

Results: In total, 40 patients were included, including 15 (37.5%), 20 (50.0%), and 5 (12.5%) on rivaroxaban, apixaban, and dabigatran, respectively. Baseline ACT was significantly lower in the apixaban group. ACT was linearly correlated with the residual concentration of apixaban and dabigatran but not with rivaroxaban. After UFH injection, ACT was linearly correlated with the anti-Xa activity, regardless of DOAC. Patients in the apixaban group received a higher total dose of UFH during the procedure to achieve a target ACT > 300 s, which resulted in significantly higher anti-Xa activity during the procedure.

Conclusion: Our results raise the question of optimal management of intra-procedural heparin therapy and highlight the limitations of the ACT test, particularly in patients on apixaban.

References

Chang R, Doherty T, Goldberg S . How does warfarin affect the activated coagulation time?. Am Heart J. 1998; 136(3):477-9. DOI: 10.1016/s0002-8703(98)70223-6. View

Hohnloser S, Camm J, Cappato R, Diener H, Heidbuchel H, Mont L . Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial. Eur Heart J. 2019; 40(36):3013-3021. PMC: 6754569. DOI: 10.1093/eurheartj/ehz190. View

Douxfils J, Gosselin R . Laboratory Assessment of Direct Oral Anticoagulants. Semin Thromb Hemost. 2017; 43(3):277-290. DOI: 10.1055/s-0036-1597296. View

Macedo K, Tatarian P, Eugenio K . Influence of Direct Oral Anticoagulants on Anti-Factor Xa Measurements Utilized for Monitoring Heparin. Ann Pharmacother. 2017; 52(2):154-159. DOI: 10.1177/1060028017729481. View

Wazni O, Rossillo A, Marrouche N, Saad E, Martin D, Bhargava M . Embolic events and char formation during pulmonary vein isolation in patients with atrial fibrillation: impact of different anticoagulation regimens and importance of intracardiac echo imaging. J Cardiovasc Electrophysiol. 2005; 16(6):576-81. DOI: 10.1111/j.1540-8167.2005.40480.x. View

Kirchhof P, Haeusler K, Blank B, De Bono J, Callans D, Elvan A . Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation. Eur Heart J. 2018; 39(32):2942-2955. PMC: 6110196. DOI: 10.1093/eurheartj/ehy176. View

Chugh S, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin E . Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2013; 129(8):837-47. PMC: 4151302. DOI: 10.1161/CIRCULATIONAHA.113.005119. View

Nagao T, Inden Y, Yanagisawa S, Kato H, Ishikawa S, Okumura S . Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation. Heart Rhythm. 2015; 12(9):1972-8. DOI: 10.1016/j.hrthm.2015.04.016. View

Calkins H, Hindricks G, Cappato R, Kim Y, Saad E, Aguinaga L . 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2017; 20(1):e1-e160. PMC: 5834122. DOI: 10.1093/europace/eux274. View

10.

Cappato R, Calkins H, Chen S, Davies W, Iesaka Y, Kalman J . Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation. 2005; 111(9):1100-5. DOI: 10.1161/01.CIR.0000157153.30978.67. View

11.

Frost C, Ly V, Garonzik S . Apixaban Pharmacokinetics and Pharmacodynamics in Subjects with Mild or Moderate Hepatic Impairment. Drugs R D. 2021; 21(4):375-384. PMC: 8602549. DOI: 10.1007/s40268-021-00359-y. View

12.

Godier A, Dincq A, Martin A, Radu A, Leblanc I, Antona M . Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J. 2017; 38(31):2431-2439. DOI: 10.1093/eurheartj/ehx403. View

13.

Konduru S, Cheema A, Jones P, Li Y, Ramza B, Wimmer A . Differences in intraprocedural ACTs with standardized heparin dosing during catheter ablation for atrial fibrillation in patients treated with dabigatran vs. patients on uninterrupted warfarin. J Interv Card Electrophysiol. 2012; 35(3):277-84. DOI: 10.1007/s10840-012-9719-9. View

14.

Briceno D, Villablanca P, Lupercio F, Kargoli F, Jagannath A, Londono A . Clinical Impact of Heparin Kinetics During Catheter Ablation of Atrial Fibrillation: Meta-Analysis and Meta-Regression. J Cardiovasc Electrophysiol. 2016; 27(6):683-93. DOI: 10.1111/jce.12975. View

15.

Martin A, Kyheng M, Foissaud V, Duhamel A, Marijon E, Susen S . Activated Clotting Time Monitoring during Atrial Fibrillation Catheter Ablation: Does the Anticoagulant Matter?. J Clin Med. 2020; 9(2). PMC: 7074080. DOI: 10.3390/jcm9020350. View

16.

Smythe M, Priziola J, Dobesh P, Wirth D, Cuker A, Wittkowsky A . Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016; 41(1):165-86. PMC: 4715846. DOI: 10.1007/s11239-015-1315-2. View

17.

Benali K, Verain J, Hammache N, Guenancia C, Hooks D, Magnin-Poull I . Running after Activated Clotting Time Values in Patients Receiving Direct Oral Anticoagulants: A Potentially Dangerous Race. Results from a Prospective Study in Atrial Fibrillation Catheter Ablation Procedures. J Clin Med. 2021; 10(18). PMC: 8465849. DOI: 10.3390/jcm10184240. View

18.

Kubitza D, Roth A, Becka M, Alatrach A, Halabi A, Hinrichsen H . Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor. Br J Clin Pharmacol. 2013; 76(1):89-98. PMC: 3703231. DOI: 10.1111/bcp.12054. View

19.

Zeljkovic I, Brusich S, Scherr D, Velagic V, Traykov V, Pernat A . Differences in activated clotting time and total unfractionated heparin dose during pulmonary vein isolation in patients on different anticoagulation therapy. Clin Cardiol. 2021; 44(8):1177-1182. PMC: 8364723. DOI: 10.1002/clc.23681. View

20.

Cirincione B, Kowalski K, Nielsen J, Roy A, Thanneer N, Byon W . Population Pharmacokinetics of Apixaban in Subjects With Nonvalvular Atrial Fibrillation. CPT Pharmacometrics Syst Pharmacol. 2018; 7(11):728-738. PMC: 6263664. DOI: 10.1002/psp4.12347. View