Abstract DP255: Desirability of Outcomes Ranking of Unknown Onset Stroke Thrombolysis Guided by Advanced Imaging: An Individual Patient Data Meta-Analysis

Introduction: Meta-analyses of RCTs of intravenous alteplase (IVT) for stroke with unknown time of onset (SUTO), selected by advanced imaging have shown better functional outcomes than placebo or standard care, but with higher mortality and symptomatic intracerebral hemorrhage (SICH). A balanced assessment of benefits and harms is therefore needed. Hypothesis: Desirability of Outcome Ranking (DOOR) methods may provide a comprehensive assessment of benefits and harms that closely reflect the patient's experience in IVT for SUTO. Methods: The Evaluation of Unknown Onset Stroke Thrombolysis (EOS) collaboration included four RCTs comparing IVT with standard care or placebo. DOOR analysis was applied to individual patient-level data. Patients were assigned a DOOR rank (1-10) based on 90-day mRS, SICH, major extracranial bleeding, and lack of NIHSS improvement ≥2 points at 24 hr. Ranks were: (1) mRS 0–1 with no undesirable events; (2) mRS 0–1 with 1 event (SICH, major extracranial bleeding, or lack of NIHSS improvement); (3) mRS 0–1 with >1 events; (4) mRS 2–3 with no events; (5) mRS 2–3 with 1 event; (6) mRS 2–3 with >1 events; (7) mRS 4–5 with no events; (8) mRS 4–5 with 1 event; (9) mRS 4–5 with >1 events; (10) death. DOOR probability and win ratio were calculated. Results: Among 829 patients (420 IVT, 409 controls), DOOR probability was 0.55 (95% CI, 0.51–0.59; p = 0.011) and win ratio was 1.24 (95% CI, 1.22-1.25), indicating a 55% probability and a 1.24 times higher frequency of achieving a more desirable outcome with IVT compared with control (Fig 1, 2). A forest plot shows that IVT was associated with a lower proportion of patients with poor functional outcome (mRS 4–5: 15.0% vs. 21.5%) and a higher proportion of NIHSS improvement (57.6% vs. 48.9%), but a higher rate of death (6.4% vs. 3.4%) and SICH/major extracranial bleeding (3.3% vs. 0.5%) compared to controls (Fig 2). Additionally, a sequential dichotomization analysis of DOOR rankings revealed that the DOOR probability remained above 50% across most dichotomization thresholds. The greatest separation was observed at DOOR > 4 vs. ≤4, with a probability of 54.8% (95% CI, 51.4–58.1) (Fig 3). Conclusions: DOOR analysis demonstrated a more desirable overall outcome with IVT for SUTO. The results suggest that IVT was associated with more favorable DOOR ranking, particularly within the better DOOR ranking strata that reflect a favorable balance between clinical efficacy and safety.