Background: and Purpose We aimed to evaluate whether early versus late initiation of direct oral anticoagulant (DOAC) after acute ischemic stroke (AIS) yields different safety and efficacy outcomes in Asian versus non-Asian patients. Methods: We analyzed Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN) trial data from 2,013 AIS patients with atrial fibrillation (AF) randomized to early (≤48 hours for minor/moderate stroke, 6–7 days for major stroke) or late DOAC initiation (3–4 days for minor ischemic stroke, 6–7 days for moderate ischemic stroke, 12–14 days for major ischemic stroke). Patients were categorized by region as Asian (Japan and India) or non-Asian. The primary outcome was a composite of major extracranial bleeding, symptomatic uncerintracranial hemorrhage (SICH), recurrent ischemic stroke, systemic embolism (SE), or vascular death at 30 days (trial registration: ClinicalTrials.gov number, NCT03148457). Results: Among 1,975 patients, 245 were Asian (192 from Japan and 53 from India) and 1,730 were non-Asian. The primary outcome occurred in 6.5% of Asian patients (4.8% early vs. 8.3% late) and 3.1% of non-Asian patients (2.7% vs. 3.6%) (p<0.01). Higher rates of recurrent ischemic stroke (4.1% [2.4% vs. 5.8%] vs. 1.7% [1.3% vs. 2.1%], p=0.02) and SE (2.0% [0.8% vs. 3.3%] vs. 0.5% [0.4% vs. 0.6%], p=0.02) accounted for this difference. No significant differences were observed in major extracranial bleeding, SICH, recurrent ischemic stroke, SE, or vascular death. No significant interaction was observed between region and treatment allocation. Conclusions Although Asian patients had worse baseline profiles and outcomes, treatment effects did not differ by region, supporting the generalizability of early DOAC initiation in Asian AIS patients without region-specific timing modifications.

BACKGROUND: Our previous observational cohort study, the Kashima Scan Study (KSS), identified associations between lifestyle, cerebral small vessel disease (SVD) as detected by magnetic resonance imaging of the brain, and disease outcomes including cognitive impairment and vascular diseases. However, established modifiers of the outcomes such as genetic background, drinking and exercise habits, and socioeconomic status were not considered. Regarding genetic factors in particular, the ALDH2 rs671 variant, East Asian-specific diversity, and APOE status are expected to have strong effects. The aim of KSS-2 is to examine the interactions of genetic background, lifestyle factors including drinking habit, socioeconomic status, and/or SVD markers for cognitive impairment, vascular disease, and death. METHOD: The KSS-2 is a prospective regional observational study of a healthy Japanese cohort that will clarify lifestyle habits to better maintain brain health from midlife by genotype. Japanese adults who underwent brain health checkups at their own expense are enrolled and will be followed-up for 10 years. We will extend the protocol of the KSS to include genetic background and potential confounding factors, including lifestyle (including drinking and exercise habit) and socioeconomic status, and perform survival analyses. The study outcomes are cognitive impairment, vascular events, and death. RESULTS: We enrolled 908 healthy adults (mean age 64.2 years; range 35 to 84 years; 41% male) from September 1, 2018 until December 31, 2024. CONCLUSION This study will provide important insights into the development of individualized health intervention strategies.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cerebral Small Vessel Diseases/diagnostic imaging* ; Japan/epidemiology* ; Life Style ; Magnetic Resonance Imaging ; Prospective Studies ; Observational Studies as Topic