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Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Background/Aims: Guidelines suggest initiating anticoagulation after cardioembolic stroke within 4-14 days from the index event. Data supporting this suggestion did not account for important factors such as infarct burden or early hemorrhagic transformation. Methods: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with an acute cardioembolic stroke in the setting of atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and the primary outcome was the composite endpoint of recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), or major extracranial hemorrhage (ECH) within 90 days. Results: We enrolled 2090 patients from 8 comprehensive centers in the United States, 1325 met the inclusion criteria (362 were excluded due to non-composite endpoint related death within 90 days, 145 lost to follow up, and 258 were not started on oral anticoagulation or the timing was not reported). Anticoagulation (875 DOAC, 404 Warfarin) was initiated in 0-3 days in 49.7%, 4-14 days in 40.4%, and >14 days in 9.9%. The combined endpoint occurred in 10.7% (142) (98 ischemic events, 21 sICH, and 30 ECH) and did not differ between the three groups: 0-3 days (11.9%), 4-14 days (9.9%), >14 days (9.9%), p=0.525. After adjusting for confounders (such as infarct volume, bridging, CHADS2-Vasc, cardiac thrombus, and hemorrhage on 24-hr imaging), oral anticoagulation timing in the 4-14 day period (vs. >14) was not associated with a reduction in ischemic events (adjusted OR 0.74, p=0.438) and oral anticoagulation timing 4-14 days (vs. 0-3) was not associated with a reduction in sICH (OR 1.28, p=0.638). Factors associated with sICH were bridging (OR 5.36, p=0.001) and hemorrhage on 24-hr imaging (OR 7.26, p Conclusion: In this multicenter real world cohort, the recommended (4-14 days) timeframe to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required determine the optimal timing of anticoagulation initiation.