Journal Article

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

Koga, Masatoshi, Cereda, Carlo W., Yoshimura, Sohei, Seiffge, David J., Acciarresi, Monica, Cappellari, Manuel, De Marchis, Gian Marco, Wilson, Duncan, Caso, Valeria, Toyoda, Kazunori, Kallmünzer, Bernd, Schaedelin, Sabine, Bonati, Leo H., Paciaroni, Maurizio, Werring, David J., Bonetti, Bruno, Macha, Kosmas, Engelter, Stefan T., Tsivgoulis, Georgios, Lyrer, Philippe

2022

Overview

ObjectiveThe 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.MethodsThis 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.ResultsA 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.ConclusionsOur 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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD
• Subject: Administration, Oral / Aged / Aged, 80 and over / Anticoagulants / Anticoagulants - therapeutic use / Atrial Fibrillation - drug therapy / Brain Ischemia - drug therapy / Cardiac arrhythmia / Cerebrovascular disease / Clinical trials / Cohort Studies / Data analysis / Europe / Female / Humans / Intracranial Hemorrhages - epidemiology / Ischemia / Ischemic Stroke - drug therapy / Japan / Male / Mortality / Observational studies / Patients / Prospective Studies / Secondary Prevention / Sensitivity analysis / Stroke / Transient ischemic attack / Variables