Clinical efficacy and mechanistic study of fulvning granules in symptomatic atrial fibrillation: A randomized controlled trial with untargeted metabolomics analysis

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and a major contributor to global morbidity and mortality. Although antiarrhythmic drugs and catheter ablation have advanced AF management, their effectiveness remains limited. Fulvning Granules (FLN), an officially approved and marketed traditional Chinese medicine for the treatment of arrhythmias, have demonstrated promising therapeutic effects in clinical practice. However, well-designed clinical trials are still needed to further confirm their efficacy and elucidate the underlying mechanisms.

Aim of the study: This study aimed to evaluate the efficacy of FLN in patients with symptomatic AF and to explore the underlying mechanisms using untargeted metabolomics analysis.

Materials and methods: A randomized, double-blind, placebo-controlled trial enrolled 136 symptomatic AF patients, who received either FLN or a placebo for one month. The primary endpoint was AF control effectiveness, assessed by 24-hour Holter monitoring. Secondary endpoints included palpitation frequency and duration, echocardiographic evaluation of cardiac structure and function, NT-pro BNP levels, Hamilton Anxiety (HAMA) and Depression (HAMD) Scales, and the 36-item Short-Form Health Survey (SF-36) from baseline to week 4. To further validate FLN’s efficacy and explore its mechanisms, serum-based metabolic pathway analysis was conducted to investigate the metabolic network associated with FLN treatment of AF. Results: FLN significantly improved AF control compared to placebo (78.57% vs. 54.39%; P=0.001). Subgroup analysis confirmed its efficacy in both paroxysmal (77.14% vs. 54.05%, P=0.048) and permanent AF (80.95% vs. 55.00%, P=0.018). FLN also reduced heart palpitations more effectively (P<0.005) and enhanced HAMA, HAMD, and SF-36 scores in paroxysmal AF(P<0.05). Metabolomics analysis identified ketone body metabolism and butanoate pathways as key targets of FLN (P<0.05).

Conclusion: Our findings suggest that FLN reduces AF episode frequency and ventricular rates, potentially through its effects on energy metabolism.

Dr. Qiong Wu is a cardiologist specializing in integrative medicine for cardiovascular diseases. She holds an M.D. and Ph.D. from Shanghai University of Traditional Chinese Medicine and serves as Associate Chief Physician at Longhua Hospital. She is a master’s supervisor at the same university and conducted a one-year visiting study at the University of Chicago. Dr. Wu leads several national research projects, has been recognized by municipal talent programs, and has authored over 30 peer-reviewed papers, including SCI-indexed publications. She is also the co-editor or contributor to two academic books.