Supracardiac Atherosclerosis in Embolic Stroke of Undetermined Source

The Underestimated Source

George Ntaios; Max Wintermark; Patrik Michel


Eur Heart J. 2021;42(18):1789-1796. 

In This Article

Gaps of Evidence and Directions for Future Research

The evidence about the role of supracardiac atherosclerosis in patients with ESUS is accumulating, but there are still many questions which remain unanswered. An important point is the assessment of the value of plaque characteristics in stroke risk stratification and subsequently, in clinical decision-making. Several ongoing prospective studies are expected to provide more evidence on this topic.[57–60]

In addition, the optimal intensity of antithrombotic treatment in these patients is unclear. More aggressive antithrombotic treatment in patients with carotid stenosis was associated with more benefits in the early phase after TIA and minor stroke[40] and in the stable-chronic phase.[42,61] In the COMPASS trial, the effect of low-dose rivaroxaban plus aspirin on ischaemic outcomes exceeded the associated increase in bleeding outcomes in patients with stable atherosclerotic disease. However, it may be possible that the embolic risk is not as high in ESUS patients who have carotid plaques of mild stenosis, even if they have high-risk features. This could result in lower absolute risk reductions of ischaemic outcomes and therefore, the overall net benefit could perhaps be neutral. Hence, further research is warranted to confirm the hypothesis that ESUS patients who have atheromatous plaques with high-risk features benefit from more aggressive antithrombotic treatment. Moreover, novel antithrombotics could be investigated in this population, such as factor XIa inhibitors. Currently, the AXIOMATIC-SSP trial (Oral Factor XIa Inhibitor for the Prevention of New Ischaemic Stroke in Patients Receiving Aspirin and Clopidogrel Following Acute Ischaemic Stroke or Transient Ischaemic Attack) aims to determine whether the addition of an oral factor XIa inhibitor to aspirin and clopidogrel is more effective than standard therapy in secondary stroke prevention in patients with acute stroke and cervical, intracranial, or aortic atherosclerosis ( NCT03766581).

Furthermore, the intensity, timing, and methods of interventions to modify lifestyle before and after ESUS need to be better studied and defined.