Anticoagulation using the direct factor Xa inhibitor apixaban during Atrial Fibrillation catheter Ablation: comparison to VKA therapy - AXAFA – AFNET 5

Contribution To Literature:

The AXAFA – AFNET 5 trial showed that apixaban is noninferior to VKA for the composite clinical endpoint with no differences in cognitive function among patients undergoing first-time catheter ablation for AF.


The goal of the trial was to compare the safety and efficacy of apixaban compared with vitamin K antagonists (VKAs) in changing cognitive function and magnetic resonance imaging (MRI)-detected brain lesions among patients undergoing catheter ablation for atrial fibrillation (AF).

Study Design

Patients undergoing first-time catheter ablation for AF and with ≥1 risk factor for stroke were randomized in a 1:1 fashion to either apixaban 5 mg BID (n = 338) or VKA (n = 336).

  • Total screened: 676
  • Total number of enrollees: 674
  • Duration of follow-up: 90 days
  • Median patient age: 64 years
  • Percentage female: 33%

Inclusion criteria:

  • Nonvalvular AF (electrocardiogram-documented) with a clinical indication for catheter ablation
  • Clinical indication to undergo catheter ablation on continuous anticoagulant therapy
  • Presence of ≥1 of the CHADS2 stroke risk factors
  • Age ≥18 years

Exclusion criteria:

  • Valvular AF
  • Prior mitral valve repair
  • Any stroke within 14 days before randomization
  • Any previous ablation or surgical therapy for AF
  • Cardiac ablation therapy for any indication (catheter-based or surgical) within 3 months prior to randomization
  • Concomitant treatment with drugs that are strong dual inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) or strong dual inducers of CYP3A4 and P-gp
  • Clinical need for triple therapy (combination therapy of clopidogrel, acetylsalicylic acid, and oral anticoagulation)
  • Other contraindications for use of VKA or apixaban
  • Documented atrial thrombi <3 months prior to randomization
  • Severe chronic kidney disease with an estimated glomerular filtration rate <15 ml/min
  • Drug abuse or clinically manifest alcohol abuse
  • Any disease that limits life expectancy to <1 year

Other salient features/characteristics:

  • Mean CHA2DS2-VASc score: 2.4; median 2.0
  • Prior stroke/transient ischemic attack (TIA): 7.4%
  • Statin use: 36.5%
  • Antiplatelet/nonsteroidal anti-inflammatory drug use: 4.7%
  • Paroxysmal AF: 58%
  • Radiofrequency ablation: 63.5%, cryoablation: 29.3%

Principal Findings:

The primary outcome, composite of all-cause mortality, stroke, or major bleeding at 90 days, for apixaban vs. VKA, was 6.9% vs. 7.3%, p for noninferiority = 0.0002.

  • Death: 0.3% vs. 0.3%
  • Stroke/TIA: 0.6% vs. 0
  • Major bleeding: 6.2% vs. 7.9%

Secondary outcomes:

  • Change in patients with abnormal Montreal Cognitive Assessment at end of study compared with baseline: -5.1% vs. -9.2%
  • Change in Short Form-12 mental component score at end of study compared to baseline, median: 0.4 vs. 1.6
  • No lesions detected on brain MRI (within 48 hours of ablation) (n = 335): 72.8% vs. 75.2%, p = 0.64


The results of this trial indicate that apixaban is noninferior to VKA for the composite clinical endpoint with no differences in cognitive function among patients undergoing first-time catheter ablation for AF. Among the subset of patients who received an MRI, new lesions were noted in nearly one quarter of patients with no difference between the two groups. This is a small but interesting trial and highlights the high subclinical embolic rates in this patient population. Changes in cognitive function over long-term follow-up would be interesting.


Kirchhof P, Haeusler KG, Blank B, et al. Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation. Eur Heart J 2018;Mar 20:[Epub ahead of print].

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Noninvasive Imaging, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Nonstatins, Novel Agents, Statins, Magnetic Resonance Imaging

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Catheter Ablation, Cognition, Electrocardiography, Factor VII, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ischemic Attack, Transient, Magnetic Resonance Imaging, Risk Factors, Secondary Prevention, Stroke, Vascular Diseases

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