Early anticoagulation in HI-1 hemorrhagic transformation after AF-associated stroke: A randomized trial

• The first randomized controlled trial (RCT) assessed early direct oral anticoagulants (DOACs) use in patients with asymptomatic hemorrhagic transformation due to atrial fibrillation. • Early anticoagulation remarkably enhanced 30 − day NIHSS and mRS scores, without a higher risk of severe bleeding. • This study complements the ELAN trial by advancing its protocol through integration of the ’1–3-6–12-day decision algorithm’ with hemorrhagic transformation (HT) subtype stratification (HI-1), thereby establishing a neuroimaging-guided, risk-adapted anticoagulation strategy. • In high − risk subgroups, rivaroxaban dosing was adjusted considering BMI, age, and potential drug interactions. • This offers vital clinical guidance for balancing thromboembolic and bleeding risks in these patients. To evaluate the safety and efficacy of early versus delayed rivaroxaban initiation in patients with atrial fibrillation (AF) and acute ischemic stroke complicated by HI-1-type hemorrhagic transformation (HT). In this multicenter, open-label, randomized controlled trial (ChiCTR2200064319), 199 patients were allocated 1:1 to early anticoagulation (EG, N = 99) or delayed anticoagulation (DG, N = 100). EG received rivaroxaban 10–20 mg/day guided by the 1–3-6–12-day rule; DG started rivaroxaban only after 2-week imaging confirmed hemorrhage resolution. The primary outcome was 30-day composite thrombotic events (CTE: ischemic stroke recurrence, systemic embolism, or all-cause mortality). Secondary outcomes included 30-day neurological recovery (NIHSS and mRS) and major bleeding (ISTH criteria). Among 180 completers (EG: 87; DG: 93), CTE rates were low and did not differ significantly (EG 1.1 % vs DG 3.2 %; HR = 0.35; 95 % CI 0.04–3.39; P = 0.37). Early anticoagulation was associated with superior neurological improvement: median NIHSS at 30 days 3.0 vs 6.0 (P = 0.001) and functional independence (mRS 0–2) 78.2 % vs 51.6 % (P < 0.001). No major bleeding events occurred in either group. In AF-related ischemic stroke with HI-1-type HT, early rivaroxaban initiation within a risk-adapted 1–3-6–12-day framework improved neurological outcomes without increasing composite thrombotic events or bleeding risk, supporting individualized early anticoagulation under neuroimaging surveillance.