Alteplase treatment in patients with minor ischemic stroke: a nationwide registry analysis.

Background: Controversy persists regarding the definition of disabling minor stroke and which patients with minor strokes may still benefit from thrombolysis. This study aimed to identify which patients with minor ischemic stroke may benefit from alteplase in a large national registry. Methods: This prospective cohort study utilized data from the Third China National Stroke Registry (CNSR-III), covering the period from August 2015 to March 2018. Participants were divided into alteplase-treated and standard medical treatment groups. Exploratory subgroup analyses were conducted across different NIHSS scores, NIHSS subitems, and TOAST subtypes. Disabling minor ischemic stroke was defined as minor stroke (NIHSS score ≤5) with consciousness impairment, motor deficits, limb ataxia or communication deficits. The primary outcome was the excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary outcomes included mRS distribution, good functional outcome (mRS score ≤2), and stroke recurrence within 90 days. Safety outcomes comprised in-hospital bleeding and 90-day mortality. Multivariable log-binomial, identity-binomial, logistic or Cox regression models were performed to assess the association between treatment and outcomes. Findings: Among a total of 2489 enrolled patients (median [IQR] age, 63 [55-70] years; 1744 [70.1%] male), 611 (24.5%) were classified into the alteplase-treated group. A total of 27 patients were excluded the complete case analysis due to incomplete mRS score at 90 days. In the overall cohort, we did not identify an effect of alteplase on the primary outcome (87.0% [524/602] vs. 83.8% [1559/1860]; unadjusted RR 1.03, 95% CI 1.00-1.07; RD 3.2%, 95% CI 0.0%-6.4%; adjusted RR 1.02, 95% CI 0.99-1.04; RD 1.8%, 95% CI -0.3% to 3.9%) among the complete case analysis (n = 2462). In patients with NIHSS>3 or disabling minor strokes (n = 849), the primary outcome occurred in 82.1% (216/263) of alteplase-treated patients compared to 74.1% (427/576) in the standard-treatment group. After adjusting for potential confounders, the patients with NIHSS >3 or disabling minor strokes in the alteplase-treated group were associated with a significantly higher risk of excellent functional outcome at 90 days (unadjusted RR 1.11, 95% CI 1.03-1.19; adjusted RR 1.12, 95% CI 1.04-1.20) and a favorable shift in the mRS score distribution (unadjusted common OR [cOR] 1.60, 95% CI 1.22-2.10; adjusted cOR 1.62, 95% CI 1.22-2.14) among the complete case analysis (n = 839). No significant differences were found in safety outcomes, including in-hospital bleeding (3.0% [8/266] vs. 1.4% [8/538]) and 90-days mortality (0.4% [1/266] vs. 2.1% [12/583]). In the combined cohort of patients with NIHSS >3, disabling minor strokes, or large artery atherosclerosis (LAA) (n = 1217), similar efficacy (e.g., excellent functional outcome: 84.2% [288/342] vs. 77.3% [666/862]; unadjusted RR 1.09, 95% CI 1.03-1.16; adjusted RR 1.11, 95% CI 1.05-1.18) and safety profiles (e.g., in-hospital bleeding: 2.9% [10/345] vs. 1.6% [14/872]) were observed. Interpretation: In the overall cohort of patients with minor ischemic stroke, no significant benefits were observed for intravenous alteplase over standard medical treatment. Further randomized controlled trials may be required to clarify the benefits of intravenous alteplase in specific clinical subgroups. Funding: This study was supported by grants from the National Natural Science Foundation of China (81870905, U20A20358) and from Beijing Hospitals Authority (QML20210501, PX2021024).