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Randomized Controlled Trial
. 2018 Aug 21;39(32):2942-2955.
doi: 10.1093/eurheartj/ehy176.

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

Paulus Kirchhof  1   2   3   4 , Karl Georg Haeusler  4   5 , Benjamin Blank  4 , Joseph De Bono  1   3 , David Callans  6 , Arif Elvan  7 , Thomas Fetsch  8 , Isabelle C Van Gelder  9 , Philip Gentlesk  10 , Massimo Grimaldi  11 , Jim Hansen  12 , Gerhard Hindricks  13 , Hussein R Al-Khalidi  14 , Tyler Massaro  15 , Lluis Mont  16 , Jens Cosedis Nielsen  17 , Georg Nölker  18 , Jonathan P Piccini  15   19 , Tom De Potter  20 , Daniel Scherr  21 , Ulrich Schotten  4   22 , Sakis Themistoclakis  23 , Derick Todd  24 , Johan Vijgen  25 , Luigi Di Biase  26   27
Affiliations
Randomized Controlled Trial

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

Paulus Kirchhof et al. Eur Heart J. .

Abstract

Aims: It is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested.

Methods and results: We compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA, international normalized ratio 2-3) in atrial fibrillation patients at risk of stroke a prospective, open, multi-centre study with blinded outcome assessment. Primary outcome was a composite of death, stroke, or bleeding (Bleeding Academic Research Consortium 2-5). A high-resolution brain magnetic resonance imaging (MRI) sub-study quantified acute brain lesions. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at baseline and at end of follow-up. Overall, 674 patients (median age 64 years, 33% female, 42% non-paroxysmal atrial fibrillation, 49 sites) were randomized; 633 received study drug and underwent ablation; 335 undertook MRI (25 sites, 323 analysable scans). The primary outcome was observed in 22/318 patients randomized to apixaban, and in 23/315 randomized to VKA {difference -0.38% [90% confidence interval (CI) -4.0%, 3.3%], non-inferiority P = 0.0002 at the pre-specified absolute margin of 0.075}, including 2 (0.3%) deaths, 2 (0.3%) strokes, and 24 (3.8%) ISTH major bleeds. Acute small brain lesions were found in a similar number of patients in each arm [apixaban 44/162 (27.2%); VKA 40/161 (24.8%); P = 0.64]. Cognitive function increased at the end of follow-up (median 1 MoCA unit; P = 0.005) without differences between study groups.

Conclusions: Continuous apixaban is safe and effective in patients undergoing atrial fibrillation ablation at risk of stroke with respect to bleeding, stroke, and cognitive function. Further research is needed to reduce ablation-related acute brain lesions.

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Figures

Figure 1
Figure 1
CONSORT diagram of the AXAFA – AFNET 5 study.
Figure 2
Figure 2
(A) Cumulative primary outcome events since randomization until 90 days after randomization at full scale (upper panel) and magnified (lower panel) in the ablation set. (B) Cumulative primary outcome events starting from ablation until 90 days after ablation at full scale (upper panel) and magnified (lower panel). VKA, vitamin K antagonist therapy.
Figure 2
Figure 2
(A) Cumulative primary outcome events since randomization until 90 days after randomization at full scale (upper panel) and magnified (lower panel) in the ablation set. (B) Cumulative primary outcome events starting from ablation until 90 days after ablation at full scale (upper panel) and magnified (lower panel). VKA, vitamin K antagonist therapy.
Figure 3
Figure 3
Forest plot of the differences (90% confidence intervals) in event rates in the main clinical subgroups. VKA, vitamin K antagonist therapy.
Figure 4
Figure 4
Examples of acute brain lesions detected in the brain magnetic resonance imaging sub-study. Acute brain lesions (arrows in A, C, E, G) are found by high-resolution diffusion-weighted brain magnetic resonance imaging without corresponding lesions in the fluid-attenuated inversion recovery images (arrows in B, D, F, H). Shown are representative lesions in two patients randomized to apixaban (A/B; C/D) and in two patients randomized to vitamin K antagonist (E/F; G/H). The fluid-attenuated inversion recovery images also detected chronic white matter lesions [asterisks (*) in F].
Take home figure
Take home figure
Cumulative outcome events in AXAFA – AFNET 5 in patients undergoing atrial fibrillation ablation at risk of stroke (top) and comparison to event rates in the two other controlled trials comparing continuous NOAC therapy with continuous vitamin K antagonist therapy (bottom). TIMI major bleeds were not separately reported in the main paper of RE-CIRCUIT. ISTH major bleeds were not separately reported in the main paper of VENTURE-AF.
None
See this image and copyright information in PMC

Comment in

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