NOAC during AF ablation associated with reduced risk of adverse outcomes

Introduction and methods

Literature - Kirchhof P, Haeusler KG, Blank B et al. - Eur Heart J 2018;39:2942–2955

Guidelines recommend continuous oral anticoagulation with vitamin K antagonists (VKA) in patients undergoing atrial fibrillation ablation (AFA), in order to reduce the risk of adverse outcomes, but it is not known whether continuous apixaban, a direct factor Xa inhibitor, provides similar protection under the same conditions [1]. AFA has been associated with a decline in cognitive function within 3 months after the procedure, as well as with silent acute brain lesions, visible on magnetic resonance imaging (MRI) [2,3].

In this prospective, randomized trial (Anticoagulation using the direct factor Xa inhibitor apixaban during Atrial Fibrillation catheter Ablation: comparison to VKA therapy, AXAFA – AFNET 5) [4], continuous apixaban was compared with continuous VKA therapy, in patients at risk of stroke undergoing AFA. Eligible patients had ≥1 stroke risk factor, such as age ≥75 years, heart failure, hypertension, diabetes, or prior stroke, and were randomized 1:1 to apixaban (5 mg b.i.d.) or VKA therapy (warfarin, phenprocoumon, or acenocoumarol, INR ≥1.8) for 30 days before the procedure and 3 months after the procedure, without interruption. Out of 674 randomized patients, 633 patients received study drug and underwent AFA. All patients underwent follow-up visits at the time of the ablation procedure and 3 months after ablation.

The primary outcome was the composite of all-cause death, stroke, or major bleeding, defined according to the Bleeding Academic Research Consortium (BARC ≥2). Bleeding was also adjudicated according to the ISTH and TIMI criteria. Secondary outcomes included changes in quality-of-life, assessed by the physical component of SF-12 and the Karnofsky scale, and changes in cognitive function compared to baseline, assessed with the Montreal Cognitive Assessment Test (MoCA) [5]. In an MRI sub-study, the prevalence and number of MRI-detected acute brain lesions were compared between groups.

Main results

  • 6.9% of patients randomized to apixaban, and 7.3% of patients randomized to VKA therapy suffered a primary endpoint event. Apixaban was non-inferior to VKA based on the non-inferiority margin of 7.5% (a difference of -0.38%; 90%CI: -4.0% to -3.3%; P[non-inferiority] = 0.0002), and based on a relative non-inferiority margin of 1.44 (equivalent to 7.5% absolute; HR: 0.88; 90%CI: 0.55-1.41; P= 0.042).
  • Four TIMI major bleedings occurred (1 on apixaban, 3 on VKA). The rate of ISTH major bleeding was 3.1% (n=10) in the apixaban and 4.4% (n=14) in the warfarin arm.
  • There was no statistically significant interaction between clinical stroke and bleeding risk factors or treatment groups.
  • Quality-of-life improved during the study without differences between study groups.
  • At baseline, 30.4% of patients had at least mild cognitive dysfunction, whereas at study end, 23.2% of patients had mild cognitive impairment. MoCA increased by a median of +1.0 (-1.0 to 2.0) unit without differences between study groups.
  • Acute brain MRI was performed in 335 patients for the MRI sub-study, out of which 323 were analyzable. Acute brain MRI lesions were found in 27.2% of patients in the apixaban group, and in 24.8% of patients in the VKA group (P=0.635). The distribution of lesions was very similar between groups.
  • There was no difference in cognitive function in patients with or without acute brain lesions (MoCA: 27.1±2.7 in 239 patients without MRI lesions; MoCA: 27.1±2.8 in 84 patients with MRI lesions; P=0.91).


Continuous apixaban therapy is a safe and effective alternative to VKA in patients at risk of stroke undergoing AFA with respect to stroke, major bleeding, cognitive function, and MRI-detected acute brain lesions.

Editorial comment

In their editorial article, Friedman and Granger [6] comment on the importance of the AXAFA-AFNET 5 study, which supports the use of uninterrupted apixaban, as an alternative to uninterrupted VKA therapy during AFA, but note that the results should be interpreted with caution, due to the low overall event number, and the wide confidence intervals. They extensively discuss the importance of silent brain lesions in about 1 of 4 patients in both study groups, although the clinical significance of these lesions is unclear in the absence of symptoms or change in cognitive function. They are potentially important because they represent acute cerebral infarction, as imaging characteristics suggest. They are somewhat disappointed that administration of apixaban, which ‘affords more reliable and consistent anticoagulation’, had no positive effect on these lesions. The authors conclude: ‘In conclusion, the AXAFA-AFNET 5 investigators have demonstrated that it is reasonable to perform AF ablation on uninterrupted apixaban, adding to the evidence that it appears safe to perform AF ablation on uninterrupted NOAC therapy. Additionally, the investigators highlight an important area for further investigation in the field of AF ablation: the critical need to better understand the significance of and how to minimize subclinical cerebral infarction.’


1. 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;37:2893–2962.

2. Schwarz N, Kuniss M, Nedelmann M, et al. Neuropsychological decline after catheter ablation of atrial fibrillation. Heart Rhythm 2010;7:1761–1767.

3. Nakamura T, Okishige K, Kanazawa T, et al. Incidence of silent cerebral infarctions after catheter ablation of atrial fibrillation utilizing the second-generation cryo-balloon. Europace 2017;19:1681–1688.

4. Di Biase L, Callans D, Hæusler KG, et al. Rationale and design of AXAFAAFNET 5: an investigator-initiated, randomized, open, blinded outcome assessment, multi-centre trial to comparing continuous apixaban to vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation. Europace 2017;19:132–138.

5. Nasreddine ZS, Phillips N, Chertkow H, et al. Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample. Neurology 2012;78:765–766; author reply 766.

6. Friedman DJ and Granger CB. Uninterrupted apixaban for atrial fibrillation ablation is a reasonable alternative, but what is the significance of silent cerebral infarctions? Eur Heart J 2018;39:2956–2958.

Find this article online at Eur Heart J

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