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.

Abstract

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.

• Authors: Gian Marco De Marchis, David J Seiffge, Sabine Schaedelin, Duncan Wilson, Valeria Caso, Monica Acciarresi, Georgios Tsivgoulis, Masatoshi Koga, Sohei Yoshimura, Kazunori Toyoda, Manuel Cappellari, Bruno Bonetti, Kosmas Macha, Bernd Kallmünzer, Carlo W Cereda, Philippe Lyrer, Leo H Bonati, Maurizio Paciaroni, Stefan T Engelter, David J Werring
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 93 Issue 2 Pg. 119-125 (02 2022) ISSN: 1468-330X [Electronic] England
• PMID: 34635567 (Publication Type: Journal Article, Observational Study)
• Copyright: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Anticoagulants

Topics

• Administration, Oral
• Aged
• Aged, 80 and over
• Anticoagulants (therapeutic use)
• Atrial Fibrillation (drug therapy)
• Brain Ischemia (drug therapy)
• Cohort Studies
• Europe
• Female
• Humans
• Intracranial Hemorrhages (epidemiology)
• Ischemic Stroke (drug therapy)
• Japan
• Male
• Prospective Studies
• Secondary Prevention