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Advanced Neurology ESUS, atrial fibrillation, and recurrence

Overall, 12-month stroke recurrence occurred in eight trials on DOACs in this context. Notably, the 12-month
patients (5%); five of 82 patients (6%) with detected SAF, stroke recurrence rate associated with antiplatelet therapy
and three of 77 patients (3.9%) without detected SAF during in ESUS patients is nearly 5%, similar to that observed
follow-up (P = 0.7205). Notably, among the five patients in overall patients with atrial fibrillation not undergoing
with detected SAF and stroke recurrence during the anticoagulant prevention. Thus, strategic planning of
1,2
12-month follow-up, two experienced stroke recurrence device positioning based on priority stratification and
despite secondary anticoagulant prevention. Specifically, monitoring duration, along with ensuring the availability
one patient had recurrence before starting OAC, while of devices, is of paramount importance.
the other experienced recurrence during anticoagulant In the present study, we focused on a real-life experience
withdrawal due to gastrointestinal bleeding. Therefore, in diagnostic work-up, management, and outcome of a
the rate of stroke recurrence in patients on OAC was 3.7% cohort of patients with ESUS. Consistent with international
compared to 6.25% in patients not on OAC (P = 0.7202). All guidelines, the majority of patients enrolled in our study
three patients with stroke recurrence while on OAC were were discharged on antiplatelet therapy for secondary
receiving apixaban full dose before stroke recurrence. No
specific risk factors for stroke recurrence were identified antithrombotic prevention. Notably, upon detection of
(Supplementary File). SAF, a significant portion of patients underwent a transition
from antiplatelet to OAC therapy, mainly comprising
4. Discussion DOACs. Our results are in agreement with those reported
in the NOR-FIB study, where all patients with SAF detected
Properly defining the etiology of ischemic stroke is of utmost through implantable loop ECG monitoring were similarly
importance for prescribing appropriate secondary prevention switched to OAC therapy. In this study, at the 12-month
treatments to reduce the risk of stroke recurrence. Despite follow-up, only 2.7% of patients experienced interruptions
baseline diagnostic work-up, approximately one-fourth of in OAC therapy. 18
ischemic stroke cases remain of undetermined etiology, with
the majority often attributed to embolic sources. Therefore, In our study, prolonged ECG monitoring was initiated
in 2014, a consensus of experts proposed the clinical approximately 4 months after the onset of stroke, with
construct of ESUS, defining its diagnostic criteria. SAF secondary prevention through OACs in patients with
14
is the main cause of ESUS identified during follow-up. In detected SAF commencing approximately 5 months’
the NOR-FIB study, conducted over a 12-month follow-up post-stroke onset. The timeframe from ESUS onset to
period, an etiology was determined in 43% of patients with ECG monitoring placement represents one of the main
ESUS, with SAF diagnosed in 29% of patients, accounting critical issues, directly proportional to the unavailability
for 67% of stroke etiologies. 15 of monitoring devices. In the Catch-Up ESUS study, the
median duration for SAF detection in ESUS patients using
As abovementioned, prolonged ECG monitoring implantable ECG or intermittent HOLTER ECG was 105
represents the gold standard for SAF detection. The (IQR = 31 – 338) days. Notably, our study defined SAF
12
19
longer the monitoring duration, the higher the likelihood based on episodes lasting at least over 30 seconds. In the
of detecting SAF. Prolonged ECG monitoring over NOR-FIB study, implantable devices were positioned after
12
3 years using implantable loop recorders can detect SAF in a median time of 9 days, with SAF diagnosis occurring
30 – 43% of patients. 10,16 However, due to the invasiveness after a mean time of 48 ± 52 days in 86.5% of patients. 18
and potential complications of implantable devices, as well
as their limited availability, only a minority of patients with The majority of stroke recurrences in ESUS patients
4-6
ESUS undergo prolonged ECG monitoring after hospital are attributed to ESUS or cardioembolic subtypes. In a
discharge. In the NOR-FIB study, complications related study involving 840 patients with a median follow-up of
17
to implantable devices were observed in 1.2% of cases, 3.7 years, atrial fibrillation emerged as a major predictor
mainly comprising local sepsis, skin perforation, and of stroke recurrence, increasing the risk by more than
18
20
subcutaneous hematoma. Due to limited availability, 2-fold. However, despite the intuitive expectation that
there may be delays in device implantation and subsequent OAC prescription following atrial fibrillation detection
analysis of ECG monitoring by physicians following a would reduce recurrence risk, current literature does not
stroke event. Such delays can increase the risk of stroke conclusively demonstrate a significant advantage of OAC in
recurrence associated with SAF. Despite the fact that OAC patients with detected SAF compared with those without it.
therapy is the appropriate secondary prevention strategy for This finding raises questions about whether prolonged ECG
patients with known atrial fibrillation, antiplatelet therapy monitoring, especially when invasive, can significantly
7
remains the recommended approach for ESUS patients impact hard outcomes such as stroke recurrence. In a meta-
due to the failure of phase III randomized controlled analysis comprising four trials with over 7000 patients,

Volume 3 Issue 1 (2024) 4 https://doi.org/10.36922/an.2287