Influence of Sex on Efficacy of Exercise Training for Patients with Symptomatic Atrial Fibrillation: Insights from the ACTIVE-AF Randomised Controlled Trial

OnlinePublAims Exercise training reduces recurrence of arrhythmia and symptom severity amongst patients with symptomatic, non-permanent atrial fibrillation (AF). However, there is little evidence on whether this effect is modified by patient sex. In a sub-analysis from the ACTIVE-AF (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation) randomized controlled trial, we compared the effects of exercise training on AF recurrence and symptom severity between men and women. Methods and results The ACTIVE-AF study randomized 120 patients (69 men, 51 women) with paroxysmal or persistent AF to receive an exercise intervention combining supervised and home-based aerobic exercise over 6 months or to continue standard medical care. Patients were followed over a 12-month period. The co-primary outcomes were recurrence of AF, off anti-arrhythmic medications and without catheter ablation, and AF symptom severity scores. By 12 months, recurrence of AF was observed in 50 (73%) men and 34 (67%) women. In an intention-to-treat analysis, there was a between-group difference in favour of the exercise group for both men [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.29–0.91, P = 0.022] and women (HR 0.47, 95% CI: 0.23–0.95, P = 0.035). At 12 months, symptom severity scores were lower in the exercise group compared with controls amongst women but not for men. Conclusion An exercise-based intervention reduced arrhythmia recurrence for both men and women with symptomatic AF. Symptom severity was reduced with exercise in women at 12 months. No difference was observed in symptom severity for men. Registration Australia and New Zealand Clinical Trials Registry: ACTRN12615000734561 Lay summary This analysis examined the potential benefit of exercise training on arrhythmia recurrence and symptom severity amongst men and women with symptomatic atrial fibrillation enrolled in a randomized controlled trial of exercise and physical activity intervention compared with standard medical care. Previous studies have not provided evidence on whether men and women might benefit from exercise training to a similar degree. Our findings highlight the following key points: • Both men and women in our study experienced fewer arrhythmia recurrences with exercise training compared with men and women in standard medical care. • Exercise reduced arrhythmia symptoms in women, but we did not find any evidence of a reduction in symptoms amongst men.Christian V. Verdicchio, Rajiv Mahajan, Melissa E. Middeldorp, Celine Gallagher, Ricardo S. Mishima, Dennis H. Lau, Prashanthan Sanders, and Adrian D. Elliot