Early apixaban safe as secondary prevention of stroke from AF

Dr Arthur Labovitz (University of South Florida, USA) presented the initial results of the pilot, open-label, parallel-group, multicentre, randomised controlled Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation (AREST) trial [1].

The study intended to determine the optimal timing of anticoagulation initiation after atrial fibrillation (AF)-induced acute ischaemic stroke (AIS), which is associated with larger infarct volumes. Previous landmark randomised trials have all waited weeks or months to begin anticoagulation after a stroke, but this trial aimed to establish the clinical value of early intervention. To that end, the safety and efficacy of early anticoagulation were evaluated based on stroke size, secondary prevention of ischaemic stroke, and risks of subsequent haemorrhagic transformation.

Patients were randomised 1:1 to receive early apixaban (n=41) at day 0–3 for transient ischaemic attack (TIA), day 3–5 for small-sized AIS (<1.5 cm), and day 7–9 for medium-sized AIS (≥1.5 cm but less than a full cortical territory), or warfarin (n=47) at 1 week post-TIA or 2 weeks after a small or medium stroke (Figure). Patients with large AIS were excluded. Enrolment was suspended prematurely after a 2019 guideline update recommended direct oral anticoagulants over warfarin in AF, excepting valvular disease.

Figure: Study schedule for the AREST study (V1 = visit 1, time 0; EOS = end of study, day 180) [2]



Reprinted from Rose DZ, et al. Front Neurol. 2019;10:975. Copyright © 2019 Rose, Meriwether, Fradley, Renati, Martin, Kasprowicz, Patel, Mokin, Murtagh, Kip, Bozeman, McTigue, Hilker, Kirby, Wick, Tran, Burgin and Labovitz.

The primary study outcome was a composite of recurrent ischaemic stroke, TIA, or fatal stroke. Key secondary outcomes were intracranial haemorrhage, haemorrhagic transformation of ischaemic stroke, cerebral microbleeds, neurologic disability (e.g. modified Rankin Scores [mRS], National Institutes of Health Stroke Scale [NIHSS], Stroke Specific Quality of Life scale [SS-QOL]), and cardiac biomarkers (e.g. AF burden, transthoracic echo/transoesophageal echo abnormalities).

At 180 days of follow up, although not statistically significant, early intervention with apixaban resulted in empirically fewer recurrent ischaemic strokes, TIAs, or fatal strokes (19.5% vs 27.7%; P=0.46). Early apixaban use was not associated with increased risk of intracranial bleeding or any of the other secondary outcomes. Dr Labovitz concluded that the early use of apixaban is safe in this patient population and may potentially be associated with improved outcomes, although further studies are warranted.

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   1. Labovitz AJ, et al. Apixaban for early prevention of recurrent embolic stroke and hemorrhagic transformation in patients with atrial fibrillation: results of the AREST trial. FS.AOS.04, AHA Scientific Sessions 2019, 14-18 November, Philadelphia, USA.
   2. Rose DZ, et al. Protocol for AREST: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation—A Randomized Controlled Trial of Early Anticoagulation After Acute Ischemic Stroke in Atrial Fibrillation. Front Neurol. 2019;10:975.

Posted on 26 February 202024 February 2021