Antioxidants for prevention of atrial fibrillation: a potentially useful future therapeutic approach? A review of the literature and meta-analysis

Atrial fibrillation (AF) is a self-perpetuating arrhythmia which is dependent upon structural and functional changes elicited by atrial high rate activity. Shortening of atrial effective refractory period is the earliest functional change which characterizes atrial remodelling. Studies in humans demonstrated oxidant species overproduction in the cardiac specimens from patients with AF and a significant association between reactive oxidant species (ROS) formation and risk of AF. Also, there is experimental evidence to suggest that ROS may be implicated not only in promoting AF but also in maintaining atrial arrhythmia. Several enzymatic pathways seem to be implicated in ROS overproduction, which ultimately leads to enhanced vulnerability to AF; they include myeloperoxidase, Nicotinamide adenine dinucleotide phosphate oxidase, and uncoupled nitric oxide synthase enzymes. To explore if ROS are implicated in promoting AF experimental studies with antioxidants, prevalently antioxidant vitamins such as ascorbic acid and vitamin E, have been planned. Furthermore, interventional trials have been carried out with antioxidants in clinical settings characterized by enhanced risk of AF. This review reports on experimental and clinical studies exploring the role of ROS in eliciting the occurrence or recurrence of AF and the potential efficacy of a treatment by antioxidant vitamins; furthermore, we performed a meta-analysis of the interventional trials in patients at risk of AF to see if antioxidant treatment is able to reduce the AF occurrence.