Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment

Vijayakumar Javalkar, MD, MCh; Okkes Kuybu, MD; Abdallah Amireh, MD; Roger E. Kelley, MD


South Med J. 2020;113(11):585-592. 

In This Article

Embolic Stroke of Undetermined Source (ESUS)

There are no clear guidelines for the management of ESUS or cryptogenic stroke. Rivaroxaban was studied for stroke prevention after an initial ESUS (NAVIGATE-ESUS, New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source).[24] Rivaroxaban at 15 mg/day was compared with aspirin at 100 mg/day, with a median follow-up of 11 months. The excluded factors were >50% stenosis of the extracranial vessels or >50% stenosis of the intracranial vessels, as well as patients younger than 49 years old. Patients in the 50- to 59-year age range were required to have at least 1 additional vascular risk factor for stroke. The primary efficacy outcome was the first recurrent stroke, and the primary safety outcome was major bleeding. There was no significant difference in the primary outcome between rivaroxaban, at an annualized rate of 5.1%, versus aspirin, at an annualized rate of 4.8% (P = 0.52, 95% CI 0.87–1.33). In addition, rivaroxaban was associated with a higher risk of bleeding, which led to the trial being stopped early.

In the RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) trial, Diener et al[25] looked at dabigatran for ESUS at 150 mg or 110 mg twice per day compared with aspirin at 100 mg/day. The primary outcome was recurrent stroke, with the primary safety outcome being major bleeding. At a median follow-up of 19 months, the rate of recurrent stroke was 4.1%/year in the dabigatran group compared with 4.8%/year in the aspirin group. Major bleeding occurred at 1.7%/year with dabigatran, compared with 1.4%/year with aspirin. Nonmajor bleeding also was higher with dabigatran, at 1.6% compared with 0.9%/year.

In summary, the identification of presumptive ESUS on clinical criteria has not translated into a clinically significant benefit with the empiric use of anticoagulant therapy, at least to date. This may indicate the need for refinement of this mechanistic but presumptive approach with further studies. Alternatively, we may need to conclude that the potential benefits are not outweighed by the risks.