Aortic Arch Related Cerebral Hazard Trial (ARCH)

Patients with Transient Ischemic attack or brain infarction of unknown cause (no ipsilateral internal carotid artery origin stenosis greater than 70%, no ipsilateral severe intracranial stenosis of an artery supplying the infarcted area, no definite cardiac source of embolism) in the preceding 6 months and atherosclerotic plaques.

≥ 4 mm in the aortic arch, or patients with a peripheral event (e.g. renal infarct) in the preceding 6 months and plaque ≥ 4 mm in the thoracic aorta above the origin of the embolized artery.

Inclusion criteria

Patients of both sexes aged ≥ 18 years with the following 4 inclusion criteria:

• One of the 3 following ischemic events in the preceding 6 months:

• Transient ischemic attack (TIA)
• Non-disabling brain infarcts:

• Inclusion within 6 months after onset
• Duration of symptoms and signs greater than 24 hours
• Neurological signs at the time of randomization with a Rankin Scale grade 3 or less
• With normal computed tomography (CT) scan or CT scan showing a brain infarct (even hemorrhagic infarct)
• Peripheral embolism
• Atherosclerotic plaque in the thoracic aorta is defined as wall thickness ≥ 4 mm where the protruding material is the largest, measured at transesophageal echocardiography with multiplane transducer or a plaque less than 4 mm but with mobile component.
• Informed consent signed
• Life expectancy > 3 years

Exclusion criteria

• Other causes of embolism:

• Cardiac: endocarditis, atrial fibrillation, intra-cardiac thrombus, valvular prosthesis, rheumatic valvulopathy, left ventricular aneurysm, or ejection fraction less than 25%
• Atherosclerotic stenosis ipsilateral to the embolic territory: internal carotid artery stenosis greater than 70%, or severe (judgment of the investigator) intracranial stenosis, or scheduled carotid endarterectomy (in that case inclusion is possible 30 days after the procedure)
• Uncommon causes: dissection, vasculitis, procoagulant state, or sickle cell disease
• Other exclusion criteria:

• Intercurrent illness with life expectancy less than 36 months
• Pregnancy and non-menopausal women
• Unwillingness to participate
• Poor medication compliance expected
• Toxicomania
• Absolute indication for anticoagulant therapy (e.g. atrial fibrillation, intracardiac thrombus, prosthetic valve)
• Scheduled for carotid endarterectomy (randomization is possible 30 days after endarterectomy)
• CT scan with an intracranial lesion other than brain infarction (space occupying mass, intracranial hemorrhage)
• Transesophageal echocardiography (TEE) with plaque ≥ 4 mm in thickness distal to the supposed embolized artery (judgement of the investigator).
• Contraindication to clopidogrel, aspirin, and oral anticoagulants