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Anticoagulation Timing in Acute Stroke With Atrial Fibrillation According to Chronic Kidney Disease: The OPTIMAS
Philip S Nash1, Hakim-Moulay Dehbi2, Norin Ahmed2
1Department of Brain Repair and Rehabilitation, Stroke Research Centre, University College London Queen Square Institute of Neurology, United Kingdom (P.S.N., L.A., J.G.B., S.M., D.J.W.).
Insights
Early direct oral anticoagulant (DOAC) initiation is safe and effective for patients with chronic kidney disease (CKD) after ischemic stroke (IS). This finding supports not withholding DOACs in CKD patients, ensuring timely stroke prevention and treatment.
Area of Science:
- Cardiology
- Neurology
- Nephrology
Background:
- Patients with chronic kidney disease (CKD) face elevated risks of ischemic stroke (IS) and intracerebral hemorrhage.
- The clinical relevance of early direct oral anticoagulant (DOAC) initiation in CKD patients with IS is significant.
Purpose of the Study:
- To investigate the safety and efficacy of early DOAC initiation in patients with IS and atrial fibrillation, specifically analyzing the impact of CKD.
- To determine if CKD modifies the treatment effect of early versus delayed DOAC initiation.
Main Methods:
- The OPTIMAS trial was a multicenter, randomized, open-label study involving patients with IS and atrial fibrillation.
- Participants were assigned to early (within 4 days) or delayed (7-14 days) DOAC initiation, with subgroup analysis for CKD presence.
- Treatment effects were assessed using mixed effects logistic regression models with interaction terms for CKD and treatment group.
Main Results:
- The study included 3601 patients, with 543 having CKD. No significant difference in the primary outcome (composite of recurrent IS, symptomatic intracranial hemorrhage, systemic arterial embolism) was observed between early and delayed DOAC initiation in either normal kidney function or CKD groups.
- Odds ratio for the primary outcome in the CKD group was 0.90 (95% CI, 0.36-2.25), with a non-significant interaction term (P=0.822).
- Secondary outcomes, including IS, symptomatic intracranial hemorrhage, and all-cause mortality, also showed no modification of treatment effect by CKD.
Conclusions:
- Chronic kidney disease (CKD) does not appear to modify the treatment effects of early versus delayed direct oral anticoagulant (DOAC) initiation following acute ischemic stroke (IS).
- These findings indicate that early DOAC initiation should not be withheld in patients with CKD.
- The results support current guidelines for anticoagulation management in IS patients with comorbid CKD.
Background:
Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of clinical relevance.
Methods:
OPTIMAS (Optimal Timing of Anticoagulation After Acute Ischemic Stroke With Atrial Fibrillation) was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7-14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality.
Results:
We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67-1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36-2.25]; Pinteraction=0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD (Pinteraction values of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively).
Conclusions:
Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.
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