The Advancing knowledge in ischemic Stroke PatiEnts on oRal Anticoagulants (ASPERA) study aims to investigate characteristics of ischemic stroke cases occurring in patients on oral anticoagulation for atrial fibrillation (AF) or other cardioembolic arrhythmias and to characterize short and long-term outcomes associated with different secondary prevention strategies to prevent stroke recurrences. The ASPERA study is a multicenter, observational, both retrospective and prospective real-world study involving acute ischemic stroke patients occurring on oral anticoagulation. The study will encompass a retrospective (ASPERA-R) and prospective (ASPERA-P) data collection. Patient will be recruited consecutively at different emergency services and stroke units worldwide. University of L'Aquila (UnivAQ) will be in charge of study coordination, data analysis and management. The duration of ASPERA-R will be of 5-year from the study initiation of the study. Participating centers will be given a 6-month timeframe to enter retrospective data, commencing from the date of study approval.

ASPERA-P duration will be of 2 years of enrollment from the study approval and follow-up of 5 years. (study conclusion after 7 years of approval). Inclusion criteria will be: 1.Confirmed diagnosis of ischemic stroke. 2. Availability of at least one neuroimaging exam positive for ischemic lesion(s) consistent with patient symptoms. 3. Ongoing oral anticoagulation at the time of the index ischemic stroke. 4. Prior diagnosis of atrial fibrillation or other cardioembolic arrhythmias. 5. Written informed consent provided by the patient himself or by proxy. Patients with Symptoms not indicative of acute stroke, ongoing intravenous or subcutaneous anticoagulation at the time of stroke will be excluded. ASPERA-R: characterization of demographic, clinical and neuroimaging features of ischemic stroke cases occurring on oral anticoagulants. The primary outcome will be: ASPERA-R : characterization of demographic, clinical and neuroimaging features of ischemic stroke cases occurring on oral anticoagulants. ASPERA-P: risk of ischemic stroke recurrence of ischemic stroke cases occurring on oral anticoagulants across different secondary preventive strategies (i.e., maintaining the same type of oral anticoagulation versus switching to a different secondary prevention strategy) at 90 days, 1 and 5 years after the index stroke. Additionally, the study will aim to investigate the risk of safety events (hemorrhagic transformation, intracranial hemorrhage, other major bleeding events, any bleeding events, death due to any cause), risk of other major ischemic events (transient ischemic attack, myocardial infarction, death due to vascular causes) at each follow-up and to identify demographic, clinical and neuroimaging features of ischemic stroke recurrences.

Inclusion Criteria:

• Age ≥18 years at the time of the index ischemic stroke.
• Confirmed diagnosis of ischemic stroke according to the World Health Organization (WHO) definition.
• Availability of at least one neuroimaging exam (either a non-contrast computed tomography [NCCT] or magnetic resonance imaging [MRI] of the brain) demonstrating one or more ischemic lesions consistent with patient symptoms.
• Ongoing oral anticoagulation at the time of the index ischemic stroke, defined as the last intake within 48 hours prior to stroke symptom onset for patients on direct oral anticoagulants (DOACs), or an international normalized ratio (INR) of ≥1.5 in patients on vitamin K antagonists (VKAs), regardless of the time elapsed between the last intake and stroke symptom onset.
• Prior diagnosis of AF or other cardioembolic arrhythmias.

Exclusion Criteria:

• Symptoms not indicative of acute stroke (i.e., syncope, tonic or clonic activity, dizziness alone, confusion and amnesia alone, chronic or subacute development of focal neurological deficit).
• Ongoing parenteral (intravenous or subcutaneous) anticoagulation at the time of the index event, including bridging with heparin in patients initiating VKA.

Patients will be enrolled from various recruiting sites worldwide. All consecutive ischemic stroke patients receiving oral anticoagulation therapy for atrial fibrillation or other cardioembolic arrhythmias at the time of the index stroke who meet the inclusion criteria will be eligible, regardless of hospitalization status. The decision to enroll a patient will be made by local investigators, who must ensure that each candidate meets the study's eligibility requirements.

We plan to share individual clinical data collected in the study with other researchers upon reasonable request, in line with ethical guidelines and data protection regulations. Data will be de-identified to protect participant confidentiality.

From the end of the ASPERA-P study (10/02/2029) up to 10 years (10/02/2039)

Access will be granted for purposes of replicating findings, conducting meta-analyses, or pursuing related research questions, subject to approval by the study's data governance committee and appropriate institutional review boards. Researchers will be required to sign data-sharing agreements to ensure proper use and compliance with confidentiality standards.