Apixaban for Treatment of Embolic Stroke of Undetermined Source

Inclusion criteria Must be ≥ 18 years at the time of signing the informed consent.

• ESUS must be defined according to following criteria:

  • Stroke detected by CT or MRI that is not lacunar
  • Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischaemia
  • No major-risk cardioembolic source of embolism
  • No other specific cause of stroke identified

• * At least one of the following non-major but suggestive risk factors for cardiac embolism:

  • LA size >45mm (parasternal axis)
  • spontaneous echo contrast in LAA
  • LAA flow velocity \<=0.2m/s
  • atrial high rate episodes
  • CHA2DS2-Vasc score >=4
  • persistent foramen ovale
• Understand and voluntarily sign an informed consent document
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception.

Exclusion Criteria:

• History of hypersensitivity to the investigational medicinal product
• Participation in other clinical trials or observation period of competing trials.
• Arteria cerebri media stroke affecting > 30% of c o r r e s p o n d i n g territory
• Diagnosis of haemorrhage or other pathology,
• Clear indication for anticoagulation
• Inability to control following risk factors for Hemorrhagic Transformation of fresh cerebral Infarction (HTI) during index hospital stay: presence of HTI at the time of anticoagulation, blood pressure >140 mmHg systolic, abnormal blood glucose Clear indication for dual antiplatelet therapy
• Clear stroke-/non-stroke-indication for concomitant long-term therapy with antiplatelets (e.g. acetylsalicylic acid (ASA), Clopidogrel, or Prasugrel) or with non-steroidal anti-inflammatory drugs (NSAID).
• Concomitant systemic therapy with strong inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e. azole antimycotics and human immunodeficiency virus (HIV)-protease inhibitors.
• Contraindication to investigational medications
• Planned or likely therapy with fibrinolytic agents within 48 hours of first study medication
• History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding
• Gastrointestinal bleed or major surgery within 3 months
• Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
• TIA or minor stroke induced by angiography or surgery
• Severe non-cardiovascular comorbidity with life expectancy \< 3 months
• Severe renal failure, defined as Glomerular Filtration Rate (GFR) \<15ml/min
• Severe hepatic insufficiency (Child-Pugh score B to C),
• Active liver disease,
• Contraindications against performance of MRI (pacemaker/ICD), previous implantation non-MRI capable protheses
• Patients considered unreliable by the investigator, or having a life expectancy less than the expected duration of the trial