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Randomized Controlled Trial
. 2022 Aug;17(7):799-805.
doi: 10.1177/17474930211058012. Epub 2021 Nov 18.

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Mukul Sharma  1 , Eric E Smith  2 , Lesly A Pearce  3 , Kanjana S Perera  1 , Scott E Kasner  4 , Byung-Woo Yoon  5 , Sebastian F Ameriso  6 , Josep Puig  7 , Dorte Damgaard  8 , Jochen B Fiebach  9 , Keith W Muir  10 , Roland C Veltkamp  11 , Danilo S Toni  12 , Nikolay Shamalov  13 , Rubens J Gagliardi  14 , Robert Mikulik  15 , Stefan T Engelter  16 , Daniel Bereczki  17 , Martin J O'Donnell  18 , Feryal Saad  2 , Ashkan Shoamanesh  1 , Scott D Berkowitz  19 , Hardi Mundl  20 , Robert G Hart  21 ; NAVIGATE ESUS MRI Substudy Investigators
Affiliations
Randomized Controlled Trial

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Mukul Sharma et al. Int J Stroke. 2022 Aug.

Abstract

Background: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown.

Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies.

Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression.

Results: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52-1.7).

Conclusions: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide.Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

Keywords: Anticoagulation; ESUS; cerebral microbleeds; covert stroke; embolic stroke; randomized clinical trial; rivaroxaban.

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Conflict of interest statement

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All co-authors or their institutions received payments from Bayer AG for participation in the NAVIGATE ESUS trial except for HM and SDB who are employed by Bayer AG.

Figures

Figure 1.
Figure 1.
MRI substudy profile.
Figure 2.
Figure 2.
Odds Ratios of Outcomes.
See this image and copyright information in PMC

References

    1. Smith EE, Saposnik G, Biessels GJ, et al. Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2017; 48: e44–e71. - PubMed
    1. Vermeer SE, Longstreth WT, Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol 2007; 6: 611–619. - PubMed
    1. Hart RG, Diener HC, Coutts SB, et al. on behalf of the Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014; 13: 429–438. - PubMed
    1. Hart RG, Sharma M, Mundl H, et al. for the NAVIGATE ESUS Steering Committee. Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: design of the NAVIGATE ESUS randomized trial. Euro Stroke J 2016; 1: 146–154. - PMC - PubMed
    1. Hart RG, Sharma M, Mundl H, for the NAVIGATE ESUS, Investigators. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med 2018; 378: 2191–2201. - PubMed

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