Subclinical atrial fibrillation: Implications of recent trials for guideline updates?

Abstract

With the widespread use of cardiac implantable electronic devices and smartwatches, device-detected atrial fibrillation (AF) also referred to as subclinical AF (SCAF) is becoming increasingly common. The incidence of device-detected AF varies between 30% and 60%, depending on the definition and the device used for detection. Multiple studies, such as EMBRACE, CRYSTAL-AF, and FIND-AF, have confirmed higher detection rates of SCAF following prolonged rhythm monitoring using implantable loop recorders or external loop recorders in patients with cryptogenic stroke. The stroke risk associated with SCAF primarily depends on two factors: The baseline CHA₂DS₂-VASc score and the duration of SCAF episodes. Very-short episodes (< 6 minutes) are likely of uncertain significance, whereas episodes lasting > 24 hours increased the risk of stroke/systemic embolism (SE) more than threefold in the ASSERT study. For episodes lasting between 6 minutes and 24 hours, the stroke risk is lower but varies with the baseline CHA₂DS₂-VASc score. Previous randomized trials of direct oral anticoagulants (DOACs) in patients with cryptogenic stroke-NAVIGATE-ESUS (with rivaroxaban) and RE-SPECT ESUS (using dabigatran)-failed to demonstrate superiority over aspirin. More recently, two dedicated studies in SCAF with DOACs have been published: NOAH-AFNET 6 (with edoxaban) and ARTESIA (with apixaban). NOAH-AFNET 6 was terminated early for futility due to slow enrollment and lower-than-expected event rates. In contrast, apixaban reduced the risk of stroke and SE by 37% in the ARTESIA study, albeit with increased bleeding. These differing results may be attributed to differences in the DOAC used, trial design, and enrolled patient populations. Current ACC/AHA guidelines recommend oral anticoagulation (OAC) for SCAF episodes lasting > 24 hours and a baseline CHA₂DS₂-VASc score > 2. For those with episodes lasting between 6 minutes and 24 hours, a higher CHA₂DS₂-VASc score > 3 points towards a benefit of OAC, while a conservative approach-including control of risk factors (e.g., hypertension, thyroid dysfunction, alcohol intake) and periodic follow-up is warranted for the rest. However, considering the positive ARTESIA results, a reevaluation may be needed. Patients with high CHA₂DS₂-VASc score (> 4) and SCAF > 24 hours duration may be ideal candidates for DOAC therapy. Those with prior stroke and vascular disease also have a higher stroke risk in future and may be attractive candidates for OAC too. For those with high bleeding risk, re-evaluation after optimizing modifiable bleeding risk factors (e.g., concomitant medications, blood pressure control) may help determine eligibility for anticoagulation. Ongoing large-scale DOAC trials will further clarify this contentious issue.

Keywords: Atrial high-rate episode; NOAH-AFNET 6; ARTESIA; Apixaban; Bleeding; CHA₂DS₂-VASc score

Core Tip: The risk of stroke in people with subclinical atrial fibrillation (SCAF) depends on: The baseline CHA₂DS₂-VASc score and the duration of the episodes. Short episodes-those lasting less than six minutes-are generally of uncertain significance. However, when the episodes last longer than 24 hours, the risk of stroke or systemic embolism increases more than threefold. The utility of oral anticoagulation, for preventing stroke in those with SCAF is still under debate. According to current ACC/AHA guidelines, oral anticoagulation is recommended for people who have SCAF episodes lasting more than 24 hours and have a high CHA₂DS₂-VASc score. For those with episodes between six minutes and 24 hours, a more cautious approach is advised-this includes managing risk factors along with regular follow-up. However, the positive results from the ARTESIA study suggest these recommendations may need to be reconsidered.