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Labovitz AJ, Rose DZ, Fradley MG, et al. Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial. Stroke. 2021 Apr;52(4):1164-1171. doi: 10.1161/STROKEAHA.120.030042. Epub 2021 Feb 25. (Original study)

BACKGROUND AND PURPOSE: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals.

METHODS: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (=1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS.

RESULTS: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm.

CONCLUSIONS: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Discipline Area Score
Hospital Doctor/Hospitalists 7 / 7
Internal Medicine 7 / 7
Neurology 6 / 7
Hemostasis and Thrombosis 5 / 7
Emergency Medicine 5 / 7
Comments from MORE raters

Hemostasis and Thrombosis rater

The small number of patients limits the value of this study.

Hospital Doctor/Hospitalists rater

Though the numbers are small, the results themselves are encouraging.

Hospital Doctor/Hospitalists rater

Clinical Question: In patients with an acute ischemic stroke (AIS) or transient ischemic attack (TIA) from atrial fibrillation, does early initiation of apixaban increase the risk of intracranial bleeds? Study Design: open-label, randomized control trial at multiple academic and private medical centers in the US. Synopsis: Patients who met inclusion criteria were randomized 1:1 to receive either early use apixiban (n=41) or warfarin (n=47). Despite the small sample size, demographics and clinical characteristics were generally comparable, except for the presence of diabetes which was notably more prevalent in the warfarin group. The primary safety endpoint was composite of fatal stroke, recurrent ischemic stroke, or TIA and secondary endpoint of intracranial hemorrhage verified by either CT or MRI. The incidence of primary composite safety outcomes were lower in the apixaban arm (17.1%) vs the warfarin arm (25.5%) with a non-significant p-value of 0.44.

Internal Medicine rater

Although the total number of subjects are small, the results show potential benefits of early apixaban: not increase the intracerebral hemorrhage, decrease the recurrence of stroke. These results may give suggestions to the clinicians in daily practice.

Neurology rater

This small trial limits interpretation but provides some evidence for earlier use of DOAC in some ischaemic strokes/TIAs in toe with AF. However, we need to await larger trials of early vs late DOAC before recommending widescale use.

Neurology rater

The AREST trial is a seminal study confirming the safety of direct oral anti-coagulants (DOAC) in TIA and small to medium stroke.
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