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 prevalent sustained arrhythmia and a leading cause of morbidity and mortality worldwide. Although antiarrhythmic drugs and catheter ablation have improved AF management, their therapeutic efficacy remains suboptimal. Fulvning Granules (FLN), a regulated hospital preparation officially approved by the Shanghai Drug Administration, have shown promising clinical efficacy in local practice. However, robust high-level clinical evidence is required to validate their benefits and elucidate the underlying mechanisms. Materials and methods A randomized, double-blind, placebo-controlled trial enrolled 136 symptomatic AF patients, who received either FLN or a placebo for 4 weeks in addition to standard guideline-directed medical therapy (GDMT). The primary endpoint was AF control effectiveness, assessed by 24-h Holter monitoring. Secondary endpoints included palpitation frequency and duration, echocardiographic evaluation of cardiac structure and function, N-terminal pro-B-type natriuretic peptide (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 with placebo (78.57% vs. 54.39%; P = 0.001), with concomitant reductions in both the frequency and duration of palpitations. In addition, treatment with FLN markedly enhanced psychological well-being and health-related quality of life. Untargeted metabolomics analysis identified 23 bioactive compounds in FLN and revealed significant modulation of ketone, butanoate, and glycerophospholipid pathways ( P < 0.05), primarily involving acylcarnitines, Lutein, and LysoPC (22:0). Conclusion FLN serves as a safe and effective adjuvant therapy for reducing AF episode frequency and ventricular rate in patients with symptomatic AF. Its mechanism may involve the modulation of cardiac energy metabolism. Clinical Trial Registration ClinicalTrials.gov, identifier ChiCTR2000036835.