Efficacy and safety of Yangxin Dingji capsule as an adjunctive therapy for atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background Yangxin Dingji Capsule (YXDJ), a modern Chinese patent medicine derived from the classic Zhigancao Decoction, is commonly used as an adjuvant therapy for atrial fibrillation (AF). This study aimed to comprehensively evaluate the efficacy and safety of YXDJ as an adjuvant therapy in AF patients. Materials and Methods We systematically searched PubMed, Embase, Web of Science, Cochrane Library, China Biology Medicine, Wanfang, VIP Chinese Journal Service Platform, and China National Knowledge Infrastructure from inception to 1 April 2026, for randomized controlled trials (RCTs) comparing YXDJ plus conventional therapy versus conventional therapy alone in patients with AF. Meta-analyses were performed using RevMan with fixed- or random-effects models based on heterogeneity. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and the overall quality of evidence for each outcome was evaluated using the GRADE framework. The protocol was registered in PROSPERO (CRD420261286691). Results Ten RCTs involving 872 patients were included. All studies were Chinese-language publications with methodological limitations. According to the RoB 2 assessment, most studies were rated as having some concerns or high risk of bias, mainly due to inadequate allocation concealment, lack of blinding for subjective outcomes, and absence of publicly available trial registrations or protocols. In terms of clinical symptoms, YXDJ was associated with improvements in the overall clinical response rate [RR = 1.27, P < 0.00001, very low], reductions in EHRA symptom scores [MD = −0.47, P = 0.0009, very low], and reductions in postoperative AF recurrence at 6 months [RR = 0.43, P = 0.03, moderate]. For cardiac function, YXDJ was associated with increases in left atrial ejection fraction (LAEF) [MD = 2.11%, P = 0.003, low] and left ventricular ejection fraction (LVEF) [MD = 4.39%, P < 0.00001, moderate], whereas no significant changes were observed in left atrial diameter (LAD) [MD = −1.97 mm, P = 0.07, very low] and mitral E/A ratio [MD = 0.12, P = 0.06, very low]; subgroup analysis revealed that YXDJ reduced LAD in postoperative patients [MD = −2.70 mm, P = 0.02, low]. In terms of inflammatory biomarkers, YXDJ was associated with reductions in hs-CRP [MD = −1.21 mg/L, P < 0.00001, low], TNF-α [SMD = −0.44, P = 0.0009, low], and IL-6 [MD = −10.42 ng/L, P < 0.00001, low]; subgroup analysis further showed a greater reduction in hs-CRP in postoperative patients [MD = −1.42 mg/L, P < 0.00001, low]. For safety, no clear increase in the overall incidence of adverse events was observed [RR = 0.58, P = 0.07, low]. Exploratory analyses from single studies suggested possible long-term benefits, including a lower reported risk of ischemic stroke and sustained reductions in AF recurrence and symptom scores at 9 months post-ablation; however, these findings are preliminary and require confirmation. Conclusion Current evidence, derived exclusively from methodologically limited, small, single-center Chinese studies, provides only preliminary signals that YXDJ may offer possible additional benefits as an adjunct to conventional therapy for symptom control and postoperative management in AF. Most efficacy outcomes were supported by low- or very-low-certainty evidence, with only LVEF and postoperative AF recurrence at 6 months rated as moderate certainty. These findings should be regarded as exploratory and hypothesis-generating. YXDJ should not replace guideline-directed anticoagulation, rate or rhythm control, or catheter ablation. Rigorously designed trials are needed to confirm its efficacy and safety. Systematic Review Identifier CRD420261286691.