Efficacy and safety of guanxinshutong capsule as adjunctive therapy for unstable angina: an integrated systematic review, meta-analysis, and network pharmacology study

Background: Unstable angina (UA), characterized by worsening chest pain and increased risk of acute myocardial infarction or sudden death, is a major clinical condition necessitating urgent and effective intervention. Although guanxinshutong capsule (GXST) has demonstrated preliminary therapeutic potential in alleviating angina symptoms, it lacks sufficient and robust clinical evidence to confirm its efficacy and safety in UA treatment. Therefore, further clinical research is urgently needed to validate the practical value of GXST in managing UA. Objective: To determine the efficacy and safety of GXST as an adjunctive therapy for UA and to elucidate its potential pharmacological mechanisms. Methods: Relevant RCTs were included to investigate the effectiveness of GXST in combination with WM for UA. ROB 2 was applied to assess their methodological quality. The data integration, evidence quality assessment, and trial sequence analysis were performed using R software, the GRADE framework, and TSA software, respectively. Concurrently, the network pharmacology was employed to identify disease-relevant targets, active components, and core targets of GXST. Crucially, bioinformatics analysis was conducted to explore the potential regulatory mechanisms. Results: Fifteen RCTs were included. Compared with WM monotherapy, GXST combined with WM exhibited significantly superior efficacy across multiple indicators: clinical effective rate(RR = 1.19, 95% CI = 1.13-1.25), ECG effective rate (RR = 1.20, 95% CI = 1.07-1.34), angina frequency (SMD = -2.20, 95% CI = -3.36 to -1.04), angina duration (SMD = -1.54, 95% CI = -2.14 to -0.94), PV levels(SMD = -0.82, 95% CI = -1.23 to -0.41), FIB levels(SMD = -1.18, 95% CI = -1.50 to -0.86), and TCM syndrome scores (SMD = -1.68, 95% CI = -2.18 to -1.18). However, no significant intergroup differences were detected in CK-MB, cTnI, or ARDI. KEGG enrichment analysis highlighted the PI3K-Akt and MAPK signaling pathways as central to the underlying mechanism. Molecular docking further demonstrated pronounced binding affinities of kaempferol, miltirone, and asiatic acid toward core targets AKT1, MAPK3, and PIK3CA, corroborating their therapeutic potential. Conclusion: The combination therapy of GXST and WM significantly boosted clinical efficacy in patients with UA. Its mechanism of action involves regulating the PIK3CA/AKT1 and MAPK3 signaling pathways. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42025634213, PROSPERO CRD42025634213.