Continuous apixaban may be safe alternative to warfarin during AF ablation
Continuous apixaban seems equally safe as warfarin and other vitamin K antagonists (VKAs) during atrial fibrillation (AF) ablation in patients at risk for stroke, according to the AXAFA–AFNET* 5 trial presented at EHRA 2018.
The primary composite endpoint of death, stroke, or BARC** 2–5 bleeding occurred at similar rates in patients randomized to apixaban or to VKAs (6.9 percent vs 7.3 percent; p=0.0002 for noninferiority). [Eur Heart J 2018;doi:10.1093/eurheartj/ehy176]
There were two deaths (one in each arm), two strokes (both in the apixaban arm), four TIMI*** major bleeds (one with apixaban), and 24 ISTH# major bleeds (10 with apixaban).
Although the noninferiority margin was wide (at a prespecified absolute margin of 0.075), lead author Professor Paulus Kirchhof of the University of Birmingham, UK, noted that this is the first controlled trial comparing a novel oral anticoagulant (NOAC) with VKA exclusively in patients at high risk of stroke.
“The results show that apixaban is a safe alternative to warfarin during catheter ablation of AF in patients at risk of stroke,” he said.
“Despite the higher stroke risk, we observed few strokes,” said Kirchhof and co-authors, who observed that two strokes (0.3 percent) occurred in AXAFA–AFNET 5, compared with one stroke (0.4 percent) in the VENTURE-AF trial (rivaroxaban vs VKA) and one transient ischaemic attack (0.2 percent) in RE-CIRCUIT (dabigatran vs warfarin). [Eur Heart J 2015;36:1805–1811; N Engl J Med 2017;376:1627-1636]
The prospective, parallel-group, open, multicentre trial included 633 patients (median age 64 years, 33 percent female) with nonvalvular AF scheduled to undergo catheter ablation and had at least one CHADS2 stroke risk factor (age ≥75 years, heart failure, prior stroke, hypertension, or diabetes). They were randomized to either continuous apixaban 5 mg twice a day or VKA (international normalized ratio 2–3). The VKAs analysed include warfarin, phenprocoumon, and acenocoumarol.
Almost one-third (30.4 percent) of the patients showed at least mild cognitive dysfunction at baseline, defined as MoCA## <26. By the end of the study, cognitive function improved overall, with 7.2 percent fewer patients having mild cognitive impairment compared with baseline (p=0.005). There was no significant difference between groups.
“This is the first randomized trial to show that cognitive function is improving after AF ablation. It is possible that this is due to continuous anticoagulation, although we did not test this specifically,” said Kirchhof.
Also, quality of life improved from baseline in both groups, without significant differences between groups.
Among the 323 patients who underwent MRI with analysable MRI scans, similar proportion of patients showed acute small brain lesions in both the apixaban and the VKA groups (27.2 percent vs 24.8 percent; p=0.635), with similar distribution.
Noting that acute brain lesions are still not completely prevented with continuous anticoagulation, the researchers believed that the lesions could have been caused by debris dislodging from ablation wounds, small thrombi, or air emboli. [Arrhythm Electrophysiol 2013;6:23-30; Circ Arrhythm Electrophysiol 2016;9:e003226]
“Procedural improvements are desirable to reduce acute brain lesions during AF ablation. Further analyses of the AXAFA–AFNET 5 data set may shed more light on risk factors for acute brain lesions in patients undergoing AF ablation on continuous anticoagulation,” suggested Kirchhof and co-authors.