Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

Abstract

AimsIt is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested.Methods and resultsWe 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.ConclusionsContinuous 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.

Minimally interrupted novel oral anticoagulant versus uninterrupted vitamin K antagonist during atrial fibrillation ablation

“…Another question is whether every NOAC is effective in preventing periprocedural thromboembolic complications. RCTs with dabigatran (RE-CIRCUIT) and rivaroxaban (VENTURE-AF) did not show any thromboembolic events [5,6], while RCTs with apixaban (AXAFA, AEIOU) showed a low thromboembolic event rate [12,21].…”

“…However, there is an increased use of NOACs in the current AF ablation population. Despite initial concerns on the safety of using periprocedural NOAC [20], nowadays, several large RCTs have demonstrated the safety and efficacy of uninterrupted use of NOACs (i.e., dabigatran, rivaroxaban, apixaban) during AF ablation [5,6,12] (Table 3). In clinical practice, however, most centers still use a minimally interrupted NOAC strategy [16].…”

“…Furthermore, continuous anticoagulation does not prevent all acute brain lesions, which can be caused by debris from ablation lesions, air emboli, or small thrombi [22]. This was demonstrated by the MRI substudy of the AXAFA trial in which acute brain lesions occurred in 27% of patients despite uninterrupted apixaban [12]. Further research is required to establish the optimal NOAC dosing strategy (minimally interrupted or uninterrupted) with regard to both bleeding and thromboembolic risk.…”

“…NOACs have several advantages, including a rapid onset of therapeutic range of anticoagulation, predictability of the anticoagulant effect, and relatively short time to reversal of anticoagulation when the medication is withheld [2]. Several observational and randomized controlled trials (RCTs) have demonstrated that uninterrupted NOAC is as safe and effective in comparison to uninterrupted VKA in patients undergoing AF ablation [3][4][5][6][7][8][9][10][11][12][13]. A recent meta-analysis demonstrated that NOAC was even associated with less major bleeding compared with VKA in pooled RCTs [14].…”

How minimally interrupted direct oral anticoagulants affect intraprocedural anticoagulation during atrial fibrillation ablation? Insights from a Japanese single‐center retrospective study

“…Calkins et al demonstrated the superiority of uninterrupted dabigatran to warfarin regarding major bleeding events in the RE‐CIRCUIT trial . Continuous apixaban and edoxaban therapies were also comparable to uninterrupted warfarin in the AXAFA‐AFNET 5 and ELIMINATE‐AF trials . Although these studies proved the noninferiority or the superiority of uninterrupted direct OACs compared with uninterrupted VKA therapy in terms of feasibility and safety, concerns remain regarding serious bleeding complications because antidotes for factor Xa inhibitors are not still readily available in many countries including Japan.…”