#2929 Early versus delayed anticoagulation in acute ischaemic stroke in those with chronic kidney disease: a pre-specified subgroup analysis of the OPTIMAS randomised controlled trial

Abstract Background and Aims The OPTIMAS trial showed that early initiation of direct oral anticoagulant (DOAC) after acute ischaemic stroke (IS) related to atrial fibrillation is non-inferior to delayed initiation. Patients with chronic kidney disease (CKD) are at increased risk of IS and intracerebral haemorrhage, so the safety and efficacy of early DOAC in those with CKD is of interest. Method OPTIMAS was a randomised, parallel-group, open-label trial with blinded outcome assessment. Participants were randomised 1:1 to early (within 4 days of onset) or delayed (at day 7–14) DOAC initiation. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial haemorrhage (sICH) and systemic arterial embolism. Secondary outcomes included the individual components of the primary outcome and all-cause mortality. CKD was defined as a history of known CKD and collected systematically. We fitted mixed effects logistic regression models with interaction terms between CKD and treatment group. Results We included 3601 patients (mean age 78.0 ± 9.9 years, 45.3% female), 543 with CKD. For the primary outcome, there was no difference between early and delayed DOAC initiation in either the normal kidney function group (OR 1.01, 95% CI 0.67 to 1.51), or the CKD group (OR 0.90, 95% CI 0.36 to 2.25), interaction P = 0.822. Similarly, for the secondary outcomes we detected no modification of the treatment effect according to CKD (interaction p-values 0.637, 0.386 and 0.107 for IS, sICH and all-cause mortality respectively). Conclusion Compared to delayed initiation of DOAC, we found no evidence of increased efficacy nor risk of harm from early DOAC initiation after acute ischaemic stroke for those with AF and CKD. OPTIMAS is registered with ClinicalTrials.gov (NCT03759938) and funded by the British Heart Foundation.