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Background and Purpose— Ischemic stroke associated with nonvalvular atrial fibrillation (NVAF) despite prior anticoagulation may indicate underlying problems that nullify the stroke-preventing effects of oral anticoagulants. We aimed to evaluate the risk for recurrent stroke in patients with NVAF with prior anticoagulation, compared with that in patients without prior anticoagulation. Methods— This study comprised pooled individual patient data on NVAF-associated acute ischemic stroke or transient ischemic attack from 2011 to 2014 arising from the Clinical Research Collaboration for Stroke in Korea (15 South Korean stroke centers) and the Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-NVAF registry (18 Japanese stroke centers). Data on 4841 eligible patients from the Clinical Research Collaboration for Stroke in Korea registry were pooled with data on all patients (n=1192) in the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry. The primary outcome was recurrent ischemic stroke. The secondary outcomes were hemorrhagic stroke and all-cause death. Outcome events were captured up to 1 year after the index event. Results— Among the 6033 patients in the full cohort, 5645 patients were analyzed, of whom 1129 patients (20.0%) had received prior anticoagulation. Median age was 75 years (interquartile range, 69–81 years), and 2649 patients (46.9%) were women. Follow-up data of 4617 patient-years (median follow-up 365 days, interquartile range 335–365 days) were available. The cumulative incidence of recurrent ischemic stroke in patients with prior anticoagulation was 5.3% (60/1129), compared with the 2.9% (130/4516) incidence in patients without prior anticoagulation. The risk for recurrent ischemic stroke was higher in patients with prior anticoagulation than in those without (multivariable Cox shared-frailty model, hazard ratio 1.50 [95% CI, 1.02–2.21]). No significant differences in the risks for hemorrhagic stroke and mortality were seen between the 2 groups. Conclusions— The risk for recurrent ischemic stroke may be higher in NVAF-associated stroke patients with prior anticoagulation than in those without prior anticoagulation. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01581502.

Background To clarify differences in clinical significance of intracardiac thrombi in nonvalvular atrial fibrillation‐associated stroke as identified by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). Methods and Results Using patient data on nonvalvular atrial fibrillation‐associated ischemic stroke between 2011 and 2014 from 15 South Korean stroke centers (n=4841) and 18 Japanese centers (n=1192), implementation rates of TEE/TTE, and detection rates of intracardiac thrombi at each center were correlated. The primary outcome was recurrent ischemic stroke at 1 year after the onset. A total of 5648 patients (median age, 75 years; 2650 women) were analyzed. Intracardiac thrombi were detected in 75 patients (1.3%) overall. Thrombi were detected in 7.8% of patients with TEE (either TEE alone or TEE+TTE: n=679) and in 0.6% of those with TTE alone (n=3572). Thrombus detection rates varied between 0% and 14.3% among centers. As TEE implementation rates at each center increased from 0% to 56.7%, thrombus detection rates increased linearly (detection rate [%]=0.11×TEE rate [%]+1.09 [linear regression], P P =0.53). Intracardiac thrombi were associated with risk of recurrent ischemic stroke overall (adjusted hazard ratio [aHR] 2.35, 95% CI, 1.07–5.16). Thrombus‐associated ischemic stroke risk was high in patients with TEE (aHR, 3.13; 95% CI, 1.17–8.35), but not in those with TTE alone (aHR, 0.89; 95% CI, 0.12–6.51). Conclusions Our data suggest clinical relevance of TEE for accurate detection and risk stratification of intracardiac thrombi in nonvalvular atrial fibrillation‐associated stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01581502.

Background There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF. Methods AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine–Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset. Results The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA). Conclusions Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF.

Introduction: We present a descriptive epidemiology data of ischemic stroke patients with atrial fibrillation from South Korea and Japan. Methods: Based on prospective registries from South Korea (CRCS-K registry) and Japan (SAMURAI-NVAF study), we collected acute ischemic stroke or transient ischemic attack (TIA) patients with documented atrial fibrillation between 2011 and 2014. Data elements, data fields, and their definitions were harmonized to generate a single dataset. A total of 6036 patients were includedin the analysis (4844 from CRCS-K and 1192 from SAMURAI-NVAF). Results: Regarding baseline characteristics, noticeable differences were found in the following variables between South Korea and Japan; mean age at onset (73.7 ± 10.1 vs 77.7 ± 9.9), TIA as an index event (2.3% vs 4.3%), diabetes (28.6% vs 20.1%), dyslipidemia (28.1% vs 32.9%), smoking (28.3% vs 36.9%), antiplatelets before stroke (39.5% vs 24.3%), anticoagulants before stroke (16.9% vs 31.8%), and recanalization treatment (31.6% vs 22.3%). Median [interquartile range] NIHSS score at admission was comparable (9 [3 - 16] vs 8 [2 - 18]). Functional recovery and event outcomes were different between two countries; mRS score 0 - 1 at 3 months (31.9% vs 36.9%), mortality at 3 months(16.8% vs 6.3%) and at 1 year (22.8% vs 15.4%) and recurrent stroke until 1 year (6.2% vs 10.6%). Conclusions: In spite of common ethnic and cultural background, ischemic stroke patients with atrial fibrillation in South Korea and Japan differ in the following points; 1) favorable recovery and event outcomes of Japanese patients in spite of older age at onset, 2) lower pre-morbid anticoagulants in South Korea, and 3) lower rate of acute recanalization treatment in Japan.