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, Gian Marco; Seiffge, David J.; Schaedelin, Sabine; Wilson, Duncan; Caso, Valeria; Acciarresi, Monica; Tsivgoulis, Georgios; Koga, Masatoshi; Yoshimura, Sohei; Toyoda, Kazunori; Cappellari, Manuel; Bonetti, Bruno; Macha, Kosmas; Kallmünzer, Bernd; Cereda, Carlo W; Lyrer, Philippe; Bonati, Leo H; Paciaroni, Maurizio; Engelter, Stefan T and Werring, David J (2022). 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. Journal of neurology, neurosurgery, and psychiatry, 93(2), pp. 119-125. BMJ Publishing Group 10.1136/jnnp-2021-327236

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OBJECTIVE

The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start.

METHODS

This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH.

RESULTS

A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke.

CONCLUSIONS

Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.

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