Efficacy and safety of Angong Niuhuang Pill in patients with acute ischemic stroke: A pilot randomized clinical trial

Ethnopharmacological relevance: Angong Niuhuang Pill (ANP) is considered a valuable first-aid treatment for ischemic stroke within Traditional Chinese Medicine, potentially offering neuroprotective effects through various pathways. However, its effectiveness in patients undergoing reperfusion therapy remains unclear. Aim of the study: This study aims to evaluate the efficacy and safety of ANP in patients diagnosed with acute ischemic stroke (AIS) caused by anterior large-vessel occlusion (LVO) undergoing endovascular therapy (EVT). Materials and methods: A pilot randomized controlled trial was conducted at a single center. Participants were randomly allocated to receive either endovascular therapy alone or endovascular therapy in conjunction with ANP (one pill per day for 14 days). The primary efficacy endpoint was modified Rankin Scale (mRS) score at 90 days, while the secondary endpoints included functional independence at 90 days, the National Institutes of Health Stroke Scale (NIHSS) scores at 14 days or discharge and improved consciousness from baseline to 5–7 days and 14 days or discharge. The primary safety endpoint was adverse events occurring within 90 days, and the secondary endpoint was all-cause mortality within 90 days. Appropriate regression models were used for endpoint analysis. Results: Of the 125 enrolled patients, 77 (61.6 %) were male, with a median age (IQR) of 72 (59–79) years. An ordinal comparison of the distribution of patients across the mRS categories showed that good functional outcome favored the ANP group (adjust common OR, 1.99 [95 % CI, 1.02–3.90]; p = 0.045). Functional independence was achieved by 64.6 % of patients in the ANP group, compared to 50.8 % in the control group (adjusted OR, 2.45 [95 % CI, 1.00–6.00]; p = 0.049). Adverse events within 90 days occurred in 27 patients (45 %) in the control group and in 23 patients (35.4 %) in the ANP group. The mortality rates were not significantly different between the two groups. Conclusions: In this trial involving patients with AIS with anterior LVO treated with EVT, the ANP group demonstrated better neurological functional outcomes along with a favorable safety profile. Additional multicenter studies are necessary to further ascertain its efficacy.