Apixaban and warfarin are equally safe during catheter ablation of atrial fibrillation, according to results of the AXAFA-AFNET 5 (Anticoagulation using the direct factor Xa inhibitor apixaban during Atrial Fibrillation catheter Ablation: Comparison to vitamin K antagonist therapy) (German Atrial Fibrillation NETwork (AFNET)) trial presented at European Heart Rhythm Association Congress (EHRA; 18–20 March 2018, Barcelona, Spain). There were similar rates of stroke and bleeding, and an improvement in cognitive function was shown for the first time.
The AXAFA-AFNET 5 trial was the first randomised trial to examine whether continuous apixaban is a safe alternative to a vitamin K antagonists (VKA) during catheter ablation of atrial fibrillation and effective in the prevention of peri-procedural complications such as death, stroke, and major bleeding events. A total of 633 patients with atrial fibrillation and additional stroke risk factors scheduled to undergo atrial fibrillation ablation in Europe and the USA were randomised to receive either continuous apixaban or the locally used VKA (warfarin, phenprocoumon, acenocoumarol, or fluindione).
The study participants received the medicine for at least 30 days prior to the planned catheter ablation procedure and medication was continued for three months after the ablation procedure. All patients were treated following the current guidelines at the time.
The primary outcome was a composite of all-cause death, stroke, and major bleeding up to three months after ablation. The primary outcome occurred in 22 patients randomised to apixaban and 23 randomised to VKA.
Paulus Kirchhof, international chief investigator of the trial, said: “The results show that apixaban is a safe alternative to warfarin during catheter ablation of atrial fibrillation in patients at risk of stroke.”
The researchers assessed cognitive function using the Montreal Cognitive Assessment test at the beginning and end of the trial and found a small but statistically significant improvement in cognitive function; it improved equally in both treatment groups. Kirchhof said: “This is the first randomised trial to show that cognitive function is improving after atrial fibrillation ablation. It is possible that this is due to continuous anticoagulation, although we did not test this specifically.”
A magnetic resonance imaging substudy in 335 patients showed a similar rate of silent strokes in the apixaban (27%) and VKA (25%) groups. Use of brain magnetic resonance imaging (MRI) was a unique feature of this study and was carried out in more than half of the study patients within 48 hours after ablation to quantify procedure-related acute ischaemic brain lesions. The results of the brain MRI substudy demonstrated no significant difference in clinically silent acute brain lesions between the treatment arms.
Kirchhof noted that patients in the trial were four years older than participants of previous studies with the non-vitamin K oral anticoagulants (NOACs) rivaroxaban and dabigatran. Other features of the trial were that local investigators chose the VKA and catheter ablation procedure which led to the use of a variety of drugs and techniques. He said: “These characteristics of the trial mean that the results apply to older patients and in different clinical settings.”
Kirchhof added: “The bleeding rate was half of what we have expected, with 22 patients experiencing events on apixaban, and 23 on VKAs, and there was a remarkably low rate of stroke, with only two events being observed in the trial (0.3%). In addition, seven episodes of cardiac tamponade–two with apixaban and five with a VKA–were managed with drainage, without the need for antidotes.”
Atrial fibrillation is associated with a high risk of stroke. Most patients with atrial fibrillation need anticoagulation therapy using VKAs or NOACs and around 5-15 % of the patients suffering from AF undergo catheter ablation treatment. During and after the ablation procedure they require anticoagulation to reduce the risk of procedure-associated stroke. Factor Xa inhibitors and direct thrombin inhibitors are new oral anticoagulants (NOACs) that provide an alternative treatment to vitamin K antagonists (VKAs) for stroke prevention in AF. Their use has previously been evaluated in several large clinical trials. Until now whether NOACs can be used in the setting of catheter ablation of AF had not been examined.