The influence of atrial high-rate episodes on stroke and cardiovascular death: an update.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias detected by continuous rhythm monitoring by pacemakers, defibrillators, or implantable cardiac monitors. Atrial high-rate episodes occur in 10-30% of elderly patients without atrial fibrillation. However, it remains unclear whether the presence of these arrhythmias has therapeutic consequences. The presence of AHRE increases the risk of stroke compared with patients without AHRE. Oral anticoagulation would have the potential to reduce the risk of stroke in patients with AHRE but is also associated with a rate of major bleeding of ∼2%/year. The stroke rate in patients with AHRE appears to be lower than the stroke rate in patients with atrial fibrillation. Wearables like smart-watches will increase the absolute number of patients in whom atrial arrhythmias are detected. It remains unclear whether anticoagulation is effective and, equally important, safe in patients with AHRE. Two randomized clinical trials, NOAH-AFNET6 and ARTESiA, are expected to report soon. They will provide much-needed information on the efficacy and safety of oral anticoagulation in patients with AHRE.

Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence.

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.

Relation of Stroke and Bleeding Risk Profiles to Efficacy and Safety of Edoxaban for Cardioversion of Atrial Fibrillation (from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation [ENSURE-AF] Study).

In the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study, edoxaban was compared with enoxaparin-warfarin in patients who underwent electrical cardioversion of nonvalvular atrial fibrillation, showing comparable low rates of bleeding and thromboembolism. The present study is an ancillary analysis investigating differences in relation to stroke and bleeding risk profiles. It also determined the relation of patients' clinical risk profiles to the quality of anticoagulation control in the warfarin arm. Primary efficacy (composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death) and safety (composite of major and clinically relevant nonmajor bleeding) outcomes and time to therapeutic range (TtTR) and time in therapeutic range (TiTR) were analyzed in relation to CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, stroke (2 points), vascular disease, age 65-74 years, sex category) and HAS-BLED (hypertension, age, stroke, bleeding tendency/predisposition, labile INRs, elderly age/frailty, drugs such as concomitant aspirin/nonsteroidal anti-inflammatory drugs or alcohol excess) scores. A total of 1,095 patients were randomized to edoxaban and 1,104 received enoxaparin-warfarin. Mean age was 64.3 ± 10 and 64.2 ± 11 years, respectively. Mean CHA2DS2-VASc score was 2.6 (standard deviation [SD] 1.5 and 1.4, respectively) and mean HAS-BLED score was 0.9 (SD 0.8) in both arms. There were nonsignificant trends toward lower odds ratios (ORs) for the efficacy end point in patients with CHA2DS2-VASc scores >2 and higher ORs with HAS-BLED score ≥3. Mean TiTR was >67%, with no differences between stroke or bleeding risk strata. The correlation between CHA2DS2-VASc and TtTR (p = 0.0286) and HAS-BLED and TiTR (p = 0.0286) were statistically significant. In patients who were at high risk of stroke, edoxaban had numerically lower primary efficacy end-point events and showed a trend for higher ORs, with HAS-BLED scores ≥3 compared with enoxaparin-warfarin. TtTR was shorter with higher CHA2DS2-VASc scores, whereas bleeding risk was inversely correlated with quality of anticoagulation control.