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.

No abstract

BackgroundOral anticoagulation prevents ischemic strokes in patients with atrial fibrillation (AF). Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients. Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not known.RationaleStroke risk is higher in pacemaker patients with AHRE than in those without, but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF. Furthermore, only a minority of patients with AHRE will develop AF, many strokes occur without a temporal relation to AHRE, and AHRE can reflect other arrhythmias than AF or artifacts. An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed.DesignThe Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence-based indications. The primary safety outcome will be major bleeding. NOAH–AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF, aged ≥65 years with at least 1 other stroke risk factor, to oral anticoagulation therapy (edoxaban) or no anticoagulation. All patients will be followed until the end of this investigator-driven, prospective, parallel-group, randomized, event-driven, double-blind, multicenter phase IIIb trial. Patients will be censored when they develop AF and offered open-label anticoagulation. The sponsor is the Atrial Fibrillation NETwork (AFNET). The trial is supported by the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research), and Daiichi Sankyo Europe.ConclusionNOAH–AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices.

Self-terminating atrial arrhythmias are commonly detected on continuous rhythm monitoring, e.g. by pacemakers or defibrillators. It is unclear whether the presence of these arrhythmias has therapeutic consequences. We sought to summarize evidence on the prevalence of atrial high-rate episodes (AHREs) and their impact on risk of stroke. We performed a comprehensive, tabulated review of published literature on the prevalence of AHRE. In patients with AHRE, but without atrial fibrillation (AF), we reviewed the stroke risk and the potential risk/benefit of oral anticoagulation. Atrial high-rate episodes are found in 10–30% of AF-free patients. Presence of AHRE slightly increases stroke risk (0.8% to 1%/year) compared with patients without AHRE. Atrial high-rate episode of longer duration (e.g. those >24 h) could be associated with a higher stroke risk. Oral anticoagulation has the potential to reduce stroke risk in patients with AHRE but is associated with a rate of major bleeding of 2%/year. Oral anticoagulation is not effective in patients with heart failure or survivors of a stroke without AF. It remains unclear whether anticoagulation is effective and safe in patients with AHRE. Atrial high-rate episodes are common and confer a slight increase in stroke risk. There is true equipoise on the best way to reduce stroke risk in patients with AHRE. Two ongoing trials (NOAH-AFNET 6 and ARTESiA) will provide much-needed information on the effectiveness and safety of oral anticoagulation using non-vitamin K antagonist oral anticoagulants in patients with AHRE.

In order to identify the effects of land-use/ cover types, soil types and soil properties on the soilatmosphere exchange of greenhouse gases (GHG) in semiarid grasslands as well as provide a reliable estimate of the midsummer GHG budget, nitrous oxide (N 2 O), methane (CH 4 ) and carbon dioxide (CO 2 ) fluxes of soil cores from 30 representative sites were determined in the upper Xilin River catchment in Inner Mongolia. The soil N 2 O emissions across all of the investigated sites ranged from 0.18 to 21.8 μg N m -2 h -1 , with a mean of 3.4 μg N m -2 h -1 and a coefficient of variation (CV, which is given as a percentage ratio of one standard deviation to the mean) as large as 130%. CH 4 fluxes ranged from -88.6 to 2,782.8 μg C m -2 h -1 (with a CV of 849%). Net CH 4 emissions were only observed from cores taken from a marshland site, whereas all of the other 29 investigated sites showed net CH 4 uptake (mean: -33.3 μg C m -2 h -1 ). CO 2 emissions from all sites ranged from 3.6 to 109.3 mg C m -2 h -1 , with a mean value of 37.4 mg C m -2 h -1 and a CV of 66%. Soil moisture primarily and positively regulated the spatial variability in N 2 O and CO 2 emissions (R 2 =0.15-0.28, P<0.05). The spatial variation of N 2 O emissions was also influenced by soil inorganic N contents (P< 0.05). By simply up-scaling the site measurements by the various land-use/cover types to the entire catchment area (3,900 km 2 ), the fluxes of N 2 O, CH 4 and CO 2 at the time of sampling (mid-summer 2007) were estimated at 29 t CO 2 -C-eq d -1 , -26 t CO 2 -C-eq d -1 and 3,223 t C d -1 , respectively. This suggests that, in terms of assessing the spatial variability of total GHG fluxes from the soils at a semiarid catchment/region, intensive studies may focus on CO 2 exchange, which is dominating the global warming potential of midsummer soil-atmosphere GHG fluxes. In addition, average GHG fluxes in midsummer, weighted by the areal extent of these land-use/cover types in the region, were approximately -30.0 μg C m -2 h -1 for CH 4 , 2.4 μg N m -2 h -1 for N 2 O and 34.5 mg C m -2 h -1 for CO 2 .