20 September 2022

A large international observational study provides compelling evidence that early administration of direct oral anticoagulants is useful.

Direct oral anticoagulants (DOACs) are standardly used after acute ischemic stroke associated with atrial fibrillation. However, the optimal time when to start administration has been unclear. There is often concern that early DOAC administration will excessively increase the risk of cerebral hemorrhage, which is why DOAC administration tends to be started late in clinical practice.

In the observational study by DKF research group leader Prof. Gian Marco De Marchis, MD, an early (≤5 days after acute ischemic stroke) versus a late DOAC start (>5 days after acute ischemic stroke) was compared in terms of recurrence rates of acute ischemic stroke as well as brain hemorrhage within 30 days.

The results do not confirm the concerns of an increased risk of cerebral hemorrhage after early DOAC initiation. Rather, the data show that there is a much higher risk of recurrent ischemic stroke when DOAC start is delayed.

First author of the publication, Prof. Gian Marco De Marchis talks about the study in the following video:


The observational study is a large analysis of 2550 patients from eight prospective European and Japanese cohort studies. The currently ongoing ELAN trial, an international multicenter randomized study, is addressing this practical issue.

ischaemic brain stroke
Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: an observational study and individual patient data pooled analysis

De Marchis, GM, Seiffge, DJ, Schaedelin, S, Wilson, D, Caso, V, Acciarresi, M, Tsivgoulis, G, Koga, M, Yoshimura, S, Toyoda, K, Cappellari, M, Bonetti, B, Macha, K, Kallmünzer, B, Cereda, CW, Lyrer, P, Bonati, LH, Paciaroni, M, Engelter, ST, & Werring, DJ

Journal of neurology, neurosurgery, and psychiatry, 93(2), 119–125

doi: 10.1136/jnnp-2021-327236. PMID: 34635567