Effect of anti-anxiety therapy on the prognosis of patients with atrial fibrillation and anxiety: a 2 × 2 factorial randomized controlled trial

Background Atrial fibrillation (AF) and anxiety frequently co-occur, significantly impairing quality of life (QoL) and potentially worsening prognosis. However, integrated psychological management in AF care remains insufficient, with scarce evidence on combined pharmacotherapy and psychological interventions. Objective This single-center, randomized controlled trial employed a 2 × 2 factorial design to evaluate the efficacy of combined anti-anxiety therapy [escitalopram and Cognitive Behavioral Therapy (CBT)] in 120 patients with AF and anxiety (GAD-7 ≥ 10). Participants were allocated to one of four groups: Drug Therapy, Psychological Intervention (CBT), Combination (Drug + CBT), or Control (routine care). The primary endpoint was the change in QoL (SF-36 questionnaire) at 3 and 6 months, and the secondary endpoint was the incidence of Major Adverse Cardiovascular Events (MACE). Results A total of 117 patients completed the follow-up. At 6 months, significant improvements were observed in the Role-Physical (RP), General Health (GH), Vitality (VT), and Social Functioning (SF) domains of the SF-36 in the intervention groups compared to the control group (all P < 0.01). Factorial analysis of the GH score change confirmed significant main effects for both psychological intervention ( P < 0.001) and drug therapy ( P = 0.011), with no significant interaction, indicating additive benefits. The Combination group also demonstrated a significantly lower overall incidence of MACE at 6 months compared to the Control group (36.67% vs. 70.00%, P = 0.003). Conclusions This study demonstrates that combined anti-anxiety pharmacotherapy and psychological therapy improves QoL and reduces cardiovascular risk in patients with AF and anxiety.