Effectiveness and safety of xingnaojing injection within 24 hours for acute ischemic stroke: a multicenter...

Acute ischemic stroke (AIS) remains a leading cause of death and disability in China. Most AIS patients are ineligible for reperfusion therapies owing to the narrow therapeutic time window and risk of bleeding complications. Xingnaojing injection (XNJI) is the only traditional Chinese medicine injection that is formally approved for prehospital stroke care. Nevertheless, high-quality real-world evidence regarding its effectiveness and safety for early use within 24 h after stroke onset remains scarce. Therefore, this prospective study aimed to explore the correlations between early XNJI administration within 24 h of symptom onset and clinical outcomes in AIS patients.

This is a multicenter prospective observational cohort study. In total, 512 AIS patients were enrolled from 10 tertiary hospitals in Beijing and were grouped according to whether XNJI was initiated within 24 h of symptom onset, split into an exposed group (XNJI combined with standard care, n = 208) and a non-exposed group (standard care alone, n = 304). The primary endpoint was early neurological deterioration (END), defined as a ≥2-point elevation in NIHSS score within 72 h post-onset. Inverse probability weighting (IPW) was used to balance baseline covariates. Following IPW adjustment, we further adjusted models for time-updated in-hospital and post-discharge concomitant treatment covariates to partially attenuate dynamic confounding during follow-up.

In the IPW-adjusted models, early XNJI administration within 24 h after the onset of AIS was associated with a reduced risk of END (adjusted odds ratio [aOR] = 0.46, 95% CI: 0.25-0.88; P = 0.018; E-value = 3.73). After adjustment, longitudinal analyses revealed significant time-by-group interactions for neurological function, functional independence and independent ADL (all P < 0.05), while the overall between-group main effects were non-significant (all P > 0.05). The two groups exhibited divergent recovery trajectories: patients receiving XNJI showed a correlative trend of more rapid improvement in neurological function at Days 3 and 10 (adjusted β ranged from -0.97 to -0.82; all P < 0.05). The XNJI group was also correlated with higher odds of achieving functional independence (modified Rankin Scale [mRS]≤2) at 1, 2, and 3 months (aOR range: 2.18-2.25; all P < 0.05) and independent activities of daily living (ADL) (Barthel Index [BI]≥90) at 2 and 3 months (aOR range: 1.49-1.62; all P < 0.05). Additionally, XNJI administration was also correlated with a reduced risk of abnormalities in neutrophil percentage (NE%) and D-dimer (all P < 0.05). No significant correlations were observed between XNJI use and in-hospital mortality, systolic blood-pressure (SBP) variation, or the risk of hepatorenal dysfunction (all P > 0.05).

This real-world observational cohort study showed that early XNJI administration within 24 h of AIS onset reduced the risk of END. Patients receiving early XNJI intervention achieved faster recovery in acute neurological function and long-term functional outcomes; however, no sustained overall therapeutic benefit was observed across all follow-up periods compared with standard stroke care alone. No significant associations were observed between XNJI and elevated risks of in-hospital mortality, SBP fluctuation or hepatorenal dysfunction. The present study only reveals observational associations, and its definite clinical efficacy and safety remain to be further verified in subsequent Randomized Controlled Trials (RCTs).

ClinicalTrials.gov, identifier NCT04275349.