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Patients who have recently had an ischemic stroke with no clear cause might have undetected atrial fibrillation (AF) that isn't caught during their initial hospital stay. After discharge, these patients are typically monitored for AF using devices like Holter monitors or implantable loop recorders. Treatment options during this period include anticoagulants or aspirin. Anticoagulants are more effective in preventing recurrent strokes if AF is present, offering an 80% risk reduction compared to aspirin's 20%. If AF is detected, anticoagulant treatment continues; if not, patients may switch to aspirin after 6-12 months. Despite the clinical rationale for using anticoagulants during this search period, their benefit-risk ratio compared to aspirin has not been fully evaluated.
Patients with recent ischemic stroke with an unknown cause may have a clinical, radiological and echocardiographic pattern of covert atrial fibrillation which is yet undetected by history, ECG monitoring or telemetry during the initial hospital stay. These patients are usually discharged with a prescription of detection of atrial fibrillation in the next weeks by either Holter ECG monitoring, or loop recorder such as wearing device or implantable device. Current standard treatment for these patients is either using anticoagulant treatment during the time of atrial fibrillation search or simply aspirin with the risk that the patient has an undetected paroxysmal atrial fibrillation with a high risk of recurrent stroke that is less prevented by aspirin (20% RRR) than by anticoagulant (80% RRR). Anticoagulant treatment in this situation is clinically justified by the fact that if the patient actually has an atrial fibrillation, an anticoagulant treatment during the search period of AF will protect the patient from a recurrent stroke, rather than treating the patient after the discovery of AF with the risk that an AF-related recurrent stroke occurs in-between. Anticoagulant treatment is then continued if atrial fibrillation is demonstrated by monitory devices, or is stopped with a switch to aspirin after 6-12 months of negative AF search, since investigators know, after NAVIGATE-ESUS and RESPECT-ESUS trials, that long-term aspirin is safer and as effective as anticoagulant in case of cryptogenic stroke.
Although anticoagulant treatment during the search period for AF makes clinically sense, and is widely used in clinical practice, its benefit/risk ratio compared to aspirin therapy has not been evaluated
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Therapeutic anticoagulation | Experimental | Choice of the investigator, VKA with target INR 2-3, or apixaban, rivaroxaban or dabigatran) |
|
| Aspirin 75-300 mg/day | Active Comparator | Aspirin is the standard of care treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apixaban | Drug | Patients who have had an ischemic stroke will receive either an anticoagulant or aspirin according to their randomization arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of fatal or nonfatal ischemic stroke, or peripheral emboli (even if asymptomatic) [peripheral emboli: emboli in arm or leg, new renal, splenic, hepatic, mesenteric infarction] | Evaluate two commonly used antithrombotic treatment strategies in patients with recent ischemic stroke and at high risk of atrial fibrillation. | During the 12 month follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity (percentage of true positives) in detecting AF | Yield and comparative rates of atrial fibrillation discovered using various tools (Holter-ECG monitoring device, loop recorder (wearing or implantable monitoring device). | long term using various tools (3 weeks) |
| The Occurrence of: Recurrent fatal or nonfatal ischemic stroke, any stroke, any stroke or TIA or vascular death |
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Inclusion Criteria:
Included patients must fulfill the following 4 criteria:
patient aged ≥65 years with:
with no known atrial fibrillation before stroke and no atrial fibrillation detected during hospital stay (monitoring or telemetry) and no mural thrombus.
but with suspected atrial fibrillation:
and a plan to detect atrial fibrillation with, long term Holter ECG, wearing device or implantable loop recorder
with a Rankin score equal or less than 4
patient has signed an informed consent
Patient is affiliated to a social security.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Philippa Lavallée, PhD | Contact | 1 40 25 87 25 | +33 | philippa.lavallee@aphp.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bichat Hospital | Recruiting | Paris | Paris | 75018 | France |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| D000083242 | Ischemic Stroke |
| D002544 | Cerebral Infarction |
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C522181 | apixaban |
| D000069552 | Rivaroxaban |
| D000069604 | Dabigatran |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
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Randomized controlled trial, open-labelled, of two standard of care therapeutic strategies: therapeutic anticoagulation (choice of the investigator, VKA with target INR 2-3, or apixaban, rivaroxaban or dabigatran) vs aspirin 75-300 mg/day
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Outcomes will be evaluated blindly by the members of the critical event committee. They will receive medical files without the patient's name, surname, phone number, or address.
|
| Aspirin | Drug | Aspirin is used as the standard of care |
|
Evaluate two commonly used antithrombotic treatment strategies in patients with recent ischemic stroke and at high risk of atrial fibrillation. |
| During the 12 month follow-up |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D020520 | Brain Infarction |
| D002545 | Brain Ischemia |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D010078 |
| Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |