OPTIMAS
Trial question
Is early initiation of DOACs noninferior to delayed initiation of DOACs in patients with AIS associated with AF?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
45.0% female
55.0% male
N = 3621
3621 patients (1640 female, 1981 male).
Inclusion criteria: adult patients with AIS associated with AF.
Key exclusion criteria: recent or current VKA anticoagulation leading to an INR ≥ 1.7; clinically significant thrombocytopenia; other coagulopathy or bleeding tendency judged to contraindicate anticoagulation; severe hemorrhagic transformation of the acute infarct or acute ICH unrelated to the acute infarct; contraindication to DOACs.
Interventions
N=1814 early DOAC initiation (initiation of DOACs within ≤ 4 days of stroke symptom onset).
N=1807 delayed DOAC initiation (initiation of DOACs at 7-14 days after stroke symptom onset).
Primary outcome
Recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism at day 90
3.3%
3.3%
3.3 %
2.5 %
1.6 %
0.8 %
0.0 %
Early DOAC
initiation
Delayed DOAC
initiation
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in recurrent ischemic stroke, symptomatic ICH, unclassifiable stroke, or systemic embolism at day 90 (3.3% vs. 3.3%).
Secondary outcomes
No significant difference in recurrent ischemic stroke (2.4% vs. 2.3%; AD 0.001%, 95% CI -0.01 to 0.01).
No significant difference in symptomatic ICH (0.6% vs. 0.7%; ARD -0.001, 95% CI -0.01 to 0).
No significant difference in all-cause mortality (8.8% vs. 8.9%; ARD -0.002, 95% CI -0.02 to 0.01).
Conclusion
In adult patients with AIS associated with AF, early DOAC initiation was noninferior to delayed DOAC initiation with respect to recurrent ischemic stroke, symptomatic ICH, unclassifiable stroke, or systemic embolism at day 90.
Reference
David J Werring, Hakim-Moulay Dehbi, Norin Ahmed et al. Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): a multicentre, blinded-endpoint, phase 4, randomised controlled trial. Lancet. 2024 Nov 02;404(10464):P1731-1741.
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