Embolic stroke of undetermined source (ESUS)

Embolic stroke of undetermined source (ESUS)

Cryptogenic Stroke/ESUS International Working Group defined embolic stroke of undetermined source (ESUS) as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation [1]. They presumed that as emboli are more likely to be thrombi, recurrence may be better prevented by anticoagulation rather than antiplatelet agents. Randomized trials with directly acting oral anticoagulants were suggested to test this hypothesis.

But two randomised trials testing this aspect, NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) as well as RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) failed to show an advantage for anticoagulation over antiplatelet agents.

Sources of emboli in ESUS could be [2]:

  1. Atrial cardiopathy
  2. Covert atrial fibrillation
  3. Left ventricular disease
  4. Atherosclerotic plaques
  5. Patent foramen ovale
  6. Cardiac valvular disease
  7. Cancer

ARCADIA trial (AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke) [3] is testing whether there is role for apixaban compared to aspirin for prevention of recurrent stroke in ESUS. Estimated enrolment is 1100 patients and expected study completion date is April 2022 [4].


  1. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, Sacco RL, Connolly SJ; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014 Apr;13(4):429-38.
  2. Ntaios G. Embolic Stroke of Undetermined Source: JACC Review Topic of the Week. J Am Coll Cardiol. 2020 Jan 28;75(3):333-340.
  3. Kamel H, Longstreth WT Jr, Tirschwell DL, Kronmal RA, Broderick JP, Palesch YY, Meinzer C, Dillon C, Ewing I, Spilker JA, Di Tullio MR, Hod EA, Soliman EZ, Chaturvedi S, Moy CS, Janis S, Elkind MS. The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods. Int J Stroke. 2019 Feb;14(2):207-214.
  4. ClinicalTrials.gov Identifier: NCT03192215.