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
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
