Abstract Mon097: Role of Oxidative Stress Modulation in Friedreich Ataxia–Associated Cardiomyopathy: A Meta-Analysis of Antioxidant Therapies

Background: Friedreich ataxia (FA), caused by frataxin deficiency, drives mitochondrial dysfunction, excess reactive oxygen species (ROS) production, and hypertrophic cardiomyopathy, the leading cause of FA mortality. We hypothesized that antioxidant therapies targeting ROS pathways would improve cardiac structural and functional parameters. Aim: To evaluate the effects of antioxidant therapies on cardiac structural and functional outcomes in FA through a systematic review and meta-analysis. Methods: A systematic search of PubMed, Embase, and the Cochrane Library identified clinical trials of antioxidant therapies in genetically confirmed FA. Twelve studies (five RCTs and seven open-label studies; n=345) were included. Antioxidant interventions included idebenone, coenzyme Q10 with vitamin E, deferiprone, and resveratrol. Outcomes included left ventricular mass index (LVMI), interventricular septal thickness, and left ventricular ejection fraction (LVEF). Pooled mean differences (MD) were estimated using random-effects models, with heterogeneity assessed by I 2 statistics. Results: Antioxidant therapy was associated with a modest but statistically significant reduction in LVMI (MD −11.07 g/m 2 , 95% CI −21.51 to −0.63, p =0.04; I 2 =45%), consistent with attenuation of hypertrophic remodeling. This effect was more pronounced in idebenone-treated cohorts (MD −16.48 g/m 2 , 95% CI −28.56 to −4.40, p =0.008; I 2 =9%). A borderline reduction in interventricular septal thickness was observed (MD −0.57 mm, 95% CI −1.14 to 0.00, p =0.05; I 2 =48%). In contrast, no significant improvement in LVEF was detected (MD 1.03%, 95% CI −8.46 to 10.52, p =0.83; I 2 =82%), with substantial heterogeneity. Conclusion: Antioxidant therapies are associated with modest improvement in structural markers of hypertrophic remodeling in FA cardiomyopathy, with idebenone showing the greatest structural effect. Systolic function (LVEF) was unchanged; substantial heterogeneity (I 2 =82%) limits interpretation of this outcome. These findings are limited by a small aggregate sample size (n=345), inclusion of open-label studies, and variable follow-up durations. Mechanistically stratified trials are warranted to address mitochondrial and iron dysregulation.