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A review article written by the NOAH – AFNET 6 investigators led by Tobias Tönnis from UKE Hamburg summarizes recent evidence on the impact of atrial high rate episodes on stroke and cardiovascular death (1). The new evidence suggests that blood thinners may not be as effective in preventing strokes as previously thought.

Implantable devices and wearables like smart-watches enable continuous or near-continuous monitoring of cardiac rhythm. This leads to detection of short arrhythmias in many people, especially elderly persons with cardiovascular conditions. These arrhythmias, called atrial high rate episodes (AHRE), look like atrial fibrillation (AF). It is well established that blood thinners (anticoagulants) provide effective stroke prevention in patients with AF. Therefore, patients with AHRE are often treated with blood thinners as well.

Dr. Tobias Toennis, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, explained: “Implanted pacemakers, defibrillators, or cardiac monitors can continuously capture and quantify atrial arrhythmias. Patients with such devices are a suitable population to study the role of infrequent atrial arrhythmias for outcomes in elderly people. AHRE occur in 10-30 % of elderly patients without atrial fibrillation. We reviewed a number of previous AHRE studies and summarized the current knowledge on stroke risk.”

A sub-study analysis of the EAST – AFNET 4 trial revealed how genetic risk for atrial fibrillation (AF) and stroke interacts with early rhythm control therapy: Early rhythm control reduces cardiovascular events in patients with AF across the spectrum of genetic AF and stroke risks. Today the findings were published in the journal Cardiovascular Research [1].

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial demonstrated that rhythm control therapy – with antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes in patients with AF and comorbidities [2]. Early rhythm control (ERC) with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome, in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.

The causes for atrial fibrillation and stroke are manifold and also comprise a heritable component. The genetic risk can be quantified by polygenic risk scores (PRS) using data from large genome-wide association studies. In a collaboration with the Broad Institute of MIT and Harvard in Cambridge, USA, these PRS were tested in the EAST – AFNET 4 study.
Dr. Shinwan Kany, University Medical Center Hamburg Eppendorf, Hamburg, Germany, explained: “Prior studies suggest that patients with a genetic predisposition to AF may suffer more recurrent AF on rhythm control therapy. Additionally, studies using PRS for stroke identified AF patients with an increase in stroke risk when otherwise classified as low risk by CHA2DS2-VASc. This information suggests that early rhythm control therapy could be less effective or less safe in patients with an elevated genomic risk for AF. To assess this, we analyzed the association between genetic AF and stroke risk and cardiovascular events in the EAST – AFNET 4 bio-sample study.”

Patients with atrial fibrillation (AF) and a history of stroke are at high risk of recurrent stroke and cardiovascular complications. Early rhythm control therapy is safe and appears particularly effective in this vulnerable patient group. This was shown by a subgroup analysis of the EAST – AFNET 4 trial. The results were published in The Lancet Neurology [1].

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial investigated whether rhythm control therapy – using antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published in 2020 [2], demonstrated that early rhythm control therapy reduced cardiovascular events by 21% in patients with AF and comorbidities: Early rhythm control (ERC) with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome, in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.

Consumer electronics provide a novel route to screen for atrial arrhythmias. The Smart in OAC – AFNET 9 study offered smartphone and wearable-based continuous arrhythmia screening to older adults and detected atrial arrhythmia in five percent of the participants. The results of the study performed by AFNET were published in the European Heart Journal of Digital Health [1].

Atrial fibrillation (AF) is the most common arrhythmia and a rising epidemic. It affects several million people in Europe. In many people the arrhythmia is asymptomatic and often remains unnoticed for a long time. However, risk of stroke and other complications may be elevated in older adults with atrial arrhythmias. Detection of atrial arrhythmias by screening potentially enables earlier therapy, to prevent complications, for example by starting anticoagulation in order to prevent strokes.

In the AXADIA – AFNET 8 trial, oral anticoagulation with the non-vitamin K antagonist oral anticoagulant (NOAC) Apixaban appeared equally safe and effective as vitamin K antagonists (VKA) in patients with atrial fibrillation (AF) and severe chronic kidney disease. The results were presented at the American Heart Association (AHA) congress on 06.11.2022 in Chicago, USA [1] and simultaneously published in Circulation [2].

AXADIA – AFNET 8 (A Safety Study Assessing Oral Anticoagulation with ApiXAban versus Vitamin KAntagonists in Patients with Atrial Fibrillation and End-Stage Kidney Disease on Chronic HemoDIAlysis Treatment) is an investigator-initiated trial with the objective of improving oral anticoagulation in patients with atrial fibrillation and chronic kidney disease on hemodialysis. It compared the NOAC Apixaban to VKA in these multimorbid patients.

Patients with atrial fibrillation (AF) and a history of stroke are at high risk of recurrent stroke and cardiovascular complications. A subgroup analysis of the EAST – AFNET 4 trial showed: Early rhythm control therapy is safe and particularly effective in this vulnerable patient group. The results were presented at the World Stroke Congress in Singapore on 26.10.2022 [1], [2].

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial investigated whether rhythm control therapy – using antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published in 2020 [3], demonstrated that early rhythm control therapy reduced cardiovascular events by 21% in patients with AF and comorbidities: Early rhythm control (ERC) with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome, in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.

The NOAH – AFNET 6 trial which is conducted to evaluate the potential benefit of oral anticoagulation in patients with atrial high rate episodes (AHRE) is going to be terminated prematurely. The reason for early termination is an observed trend towards futility for efficacy combined with expected safety concerns. Following a recommendation of the study scientific committees, on 2 September 2022, AFNET decided to orderly terminate the NOAH – AFNET6 trial in the coming weeks. The study results will be available next year.