The potential for NOACs in cardiac ablation in the UK

Introduction

PIONEER 4 Figure 1. Open irrigated catheter, with pores for flow of heparinised saline seen on the tip — Figure 1. Open irrigated catheter, with pores for flow of heparinised saline seen on the tip

Susceptibility to stroke is increased around the time of catheter ablation; with ablation of atrial fibrillation (AF) being the most prevalent electrophysiological procedure and, thus, the most studied. Pre-ablation of AF, there is an increased risk of thrombus formation in the left atrial appendage; with potential for embolisation during restoration of normal sinus rhythm.¹ During ablation, the risk of thromboembolism is accounted for by endothelial injury, hypercoagulability due to contact of blood with foreign surfaces and altered blood flow after conversion to normal sinus rhythm.² This risk persists post-ablation, even in patients with low CHA₂DS₂-VASc scores, as the atria may remain stunned for several weeks post-ablation and the endothelium takes time to heal. These phenomena form the rationale for guidelines recommending anticoagulation for four weeks before and two to three months’ post-ablation.^3,4 During the procedure intravenous (IV) heparin is used, and the use of heparinised saline-irrigated catheters (figure 1) seems to reduce risk further by decreasing the incidence of emboli from the catheter tip.⁵

Warfarin has been the mainstay of anticoagulant therapy, although its use has been impacted by the advent of non-vitamin K antagonist oral anticoagulants (NOACs), which have now been available in the UK since 2008.⁶ Their use was initially limited because of concerns about safety and the ability to reverse the anticoagulant effect if a catastrophic bleed occurred. This concern seems difficult to justify when one acknowledges that in the landmark randomised trial AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment), the frequency and severity of bleeding appeared to be similar for aspirin and apixaban.⁷ Yet aspirin has no specific reversal agent and in the only NOAC trial (RE-CIRCUIT in the setting of catheter ablation) in which a specific antidote was available – idarucizumab for dabigatran – it was not used to treat any of the patients who required medical attention.⁸

Increased knowledge of the efficacy and safety profile of NOACs has led to a 17-fold increase in the initiation of their use (from 2009–2015) – overall a 58% rate of increase in anticoagulation was seen, even though the rate of new VKA use decreased by 31% over the same period.⁹ NOACs offer more predictable pharmacodynamics and the convenience of no regular monitoring. The stable anticoagulant action could reduce stroke post-ablation and may reduce the need for pre-ablation transoesophageal echo (TOE) to exclude left atrial appendage thrombus, which is often the consequence of subtherapeutic international normalised ratio (INR) values in the run-up to ablation.¹⁰ Conversely, high INR values can also preclude ablation and it is the practice at our institute to use a cut-off INR of 3.5.

Uninterrupted anticoagulation peri-ablation is now commonplace. ‘Bridging’ with low molecular weight heparin (LWMH) was initially employed as a strategy, but has been usurped by uninterrupted warfarin, initially,¹¹ and now NOACs. This latter point has been the focus of some studies over the last few years with the outcomes being positive regarding NOAC use when compared with warfarin in an uninterrupted strategy. Studies have shown similar stroke rates, and similar or lower bleeding rates when NOACs are compared with warfarin.^8,12 It would be appropriate to speculate that other non-cardiological procedures with low bleeding risks may begin to adopt an uninterrupted peri-operative anticoagulation strategy; with procedures with an inherently higher bleeding risk maintaining the interrupted regimen.

How do we manage anticoagulation in non-AF catheter ablation cases? Guidelines suggest management of ablation of left atrial arrhythmias and cavo-tricuspid dependent atrial flutter in the same way as for AF.¹³ Ventricular tachycardia ablation management is less standardised with current recommendations for six to 12 weeks of aspirin or warfarin post-ablation, with some centres anticoagulating four to six weeks prior in patients with structural heart disease.¹⁴

Conclusion

The availability of NOACs initially caused concern about an increased bleeding risk and lack of antidote, but this has not been borne out in studies, leading to increased use in the UK. For the purposes of catheter ablation of AF, NOACs are acceptable to use and the data suggest they should be used in an uninterrupted manner. Whether this approach extends to other procedures in patients at high risk of stroke is yet to be seen.

Key messages

Warfarin has been the mainstay of anticoagulation in catheter ablation patients
Initial concerns in using non-vitamin K antagonist oral anticoagulants (NOACs) have now abated
Studies have shown similar stroke rates, and similar or lower bleeding rates for NOACs versus warfarin

Conflict of interest

None declared.

Articles in this supplement include:

Introduction
Anticoagulation in patients with non-valvular AF undergoing PCI: clinical evidence from PIONEER AF-PCI
The PIONEER AF-PCI study: its implications for everyday practice in the UK
Use of NOAC drugs in DC cardioversion for patients with non-valvular AF

References

1. McCready JW, Nun L, Lambiase PD et al. Incidence of left atrial thrombus prior to atrial fibrillation ablation: is pre-procedural transoesophageal echocardiography mandatory? Europace 2010;12:927–32. https://doi.org/10.1093/europace/euq074

2. Weitz JI, Healey JS, Skanes AC, Verma A. Periprocedural management of new oral anticoagulants in patients undergoing atrial fibrillation ablation. Circulation 2014;129:1688–94. https://doi.org/10.1161/CIRCULATIONAHA.113.005376

3. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–962. https://doi.org/10.1093/eurheartj/ehw210

4. Calkins H, Kuck KH, Cappato R et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. J Interv Card Electrophysiol 2012;33:171–257. https://doi.org/10.1007/s10840-012-9672-7

5. Gaita F, Leclercq JF, Schumacher B et al. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol 2011;22:961–8. https://doi.org/10.1111/j.1540-8167.2011.02050.x

6. National Institute for Health and Care Excellence. Anticoagulation – oral. London: NICE, 2015. Available from: https://cks.nice.org.uk/anticoagulation-oral

7. Connolly S, Eikelboom J, Joyner C et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–17. https://doi.org/10.1056/NEJMoa1007432

8. Calkins H, Willems S, Gerstenfeld EP et al. Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation. N Engl J Med 2017;376:1627–1636. https://doi.org/10.1056/NEJMoa1701005

9. Loo SY, Dell ‘Aniello S, Huiart L, Renoux C. Trend in the prescription of novel oral anticoagulants in UK primary care. Br J Clin Pharmacol 2017;83:2096–106. https://doi.org/10.1111/bcp.13299

10. Maan A, Heist EK, Ruskin JN, Mansour M. Practical issues in the management of novel oral anticoagulants – cardioversion and ablation. J Thorac Dis 2015;7:115–31. https://doi.org/10.3978/j.issn.2072-1439.2014.11.35

11. Page SP, Siddiqui MS, Finlay M et al. Catheter ablation for atrial fibrillation on uninterrupted warfarin: can it be done without echo guidance? J Cardiovasc Electrophysiol 2011;22:265–70. https://doi.org/10.1111/j.1540-8167.2010.01910.x

12. Cappato R, Marchlinski FE, Hohnloser SH et al. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 2015;36:1805–11. https://doi.org/10.1093/eurheartj/ehv177

13. Sticherling C, Marin F, Birnie D et al. Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society. Europace 2015;17:1197–214. https://doi.org/10.1093/europace/euv190

14. Aliot EM, Stevenson WG, Almendral-Garotte JM et al. EHRA/HRS expert consensus on catheter ablation of ventricular arrhythmias. Europace 2009;11:771–817. https://doi.org/10.1093/europace/eup098

Notes on dosing recommendations from Xarelto® ▼ (rivaroxaban) SmPC (Summary of Product Characteristics)

For the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors, the recommended dose is 20 mg once daily (15 mg once daily in patients with moderate [creatine clearance {CrCl} 30-49 ml/min] or severe [CrCl 15-29 ml/min] renal impairment). To be used with caution in severe renal impairment and use is not recommended in patients with CrCl <15 ml/min.

The above doses were studied in the pivotal ROCKET AF study in patients with non-valvular AF.

In the PIONEER AF-PCI study, participants with non-valvular AF who had undergone percutaneous coronary intervention (PCI) with stenting were randomly assigned to receive either rivaroxaban 15 mg once daily (10 mg once daily, CrCl 30-50 ml/min) plus a P2Y₁₂ inhibitor for 12 months, or rivaroxaban 2.5 mg twice daily plus dual antiplatelet therapy (DAPT) for one, six, or 12 months, or dose-adjusted vitamin K antagonist once daily plus DAPT for one, six, or 12 months.

The Xarelto® (rivaroxaban) SmPC has been updated under ‘Special populations’ in the section on ‘Posology and method of administration’ following completion of the PIONEER AF-PCI study; the rivaroxaban 15 mg once daily regimen, but not the 2.5 mg twice daily regimen, has been included.

In summary, the SmPC update states that for patients with non-valvular AF who require oral anticoagulation and undergo PCI with stent placement, there is limited experience of a reduced dose of rivaroxaban 15 mg once daily (10 mg once daily, CrCl 30-49 ml/min) in addition to a P2Y₁₂ inhibitor for a maximum of 12 months.