Early initiation of DOACs did not significantly reduce the 90-day composite of recurrent stroke, symptomatic intracerebral hemorrhage, or unclassified stroke (HR 0.82; 95% CI 0.64-1.04; p=0.09).
Meta-Analysis (n=6,642)
Yes
Does early initiation of DOACs reduce recurrent ischaemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke in patients with acute ischaemic stroke and atrial fibrillation compared to late initiation?
Early initiation of DOACs after acute ischemic stroke in patients with AF does not significantly reduce the composite risk of recurrent stroke or symptomatic intracerebral hemorrhage compared to late initiation.
Hazard Ratio: 0.82 (95% CI 0.64–1.04)
p-value: p=0.09
Abstract Background The timing of oral anticoagulation for preventing early recurrence of ischaemic stroke in patients with acute ischaemic stroke and atrial fibrillation is not well-defined. This uncertainty highlights the need for research to clarify the optimal initiation timing for direct oral anticoagulants (DOACs). Purpose This study aims to evaluate the effects of starting DOACs early compared to later following the onset of ischaemic stroke. Methods For this meta-analysis, we conducted a comprehensive search of major databases for randomized controlled trials (RCTs) that compared the early versus late initiation of DOACs in individuals with acute ischaemic stroke and atrial fibrillation (AF). The primary outcome was a composite measure of recurrent ischaemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke occurring within 90 days of randomization. Secondary outcomes included isolated ischemic stroke, symptomatic intracranial hemorrhage (SICH), and systemic embolism. Individual patient data were reconstructed using Kaplan-Meier curves. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through Cox regression analysis, and all endpoints were further assessed using risk ratios (RRs). Statistical analyses were performed using R software version 4.5.0. Results Four RCTs (ELAN, START, TIMING, OPTIMAS) were included comprising 6,642, of whom 3,282 (49%) were randomized to an early initiation of DOAC. Using Kaplan-Meier's analysis, no significant differences were found in the composite endpoint (HR 0.82; 95% CI: 0.64 to 1.04; p=0.09; Figure 1), ischemic stroke (HR 0.81; 95% CI: 0.60 to 1.11; p=0.19), SICH (HR 0.93; 95% CI: 0.46 to 1.89; p=0.85), and systemic embolism (HR 0.50; 95% CI: 0.21 to 1.16; p=0.11). Similar results were observed in the risk ratios analyses, reinforcing these findings (Figure 2). Conclusion Among patients with AF and a history of acute ischaemic stroke, no significant difference was observed when anticoagulation was initiated early. Further RCTs are needed to validate these findings.
Barbosa et al. (Mon,) conducted a meta-analysis in acute ischaemic stroke and atrial fibrillation (n=6,642). Early initiation of DOACs vs. Late initiation of DOACs was evaluated on composite measure of recurrent ischaemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke occurring within 90 days of randomization (HR 0.82, 95% CI 0.64-1.04, p=0.09). Early initiation of DOACs did not significantly reduce the 90-day composite of recurrent stroke, symptomatic intracerebral hemorrhage, or unclassified stroke (HR 0.82; 95% CI 0.64-1.04; p=0.09).