Letter to the Editor

The antioxidant effects of statins may extend beyond atherosclerosis: potential benefits for atrial fibrillation and heart failure

Atrial fibrillation (AF) leads to electrical atrial remodeling including alterations of various ion channels early after arrhythmia onset. The beneficial effects of statins in AF treatment due to their influence on oxidative stress and inflammation are discussed. Our hypothesis was that statins might also alter atrial ion currents and their early tachycardia-induced remodeling.

Effects of an atorvastatin treatment (7 days) on atrial ion currents and their tachycardia-induced alterations were studied in a rabbit model of tachycardia-induced electrical remodeling (rapid atrial pacing (600 min) for 24 and 120 h). Ion currents (L-type calcium channel [I_Ca,L], transient outward current [I_to]) were measured using whole cell patch clamp method and were compared with previous experiments in untreated but also tachypaced animals.

Atorvastatin treatment alone decreased I_Ca,L similar to rapid atrial pacing alone, currents were also further reduced by additional atrial tachypacing. I_to and its pacing-induced down-regulation after 24 h were not influenced by atorvastatin treatment. However, I_to was still reduced after 120 h in atorvastatin-treated animals and did not return to control values as expected.

The present study establishes that an atorvastatin treatment can affect atrial ion currents and their tachycardia-induced remodeling in a rabbit model. These results show that—amongst other positive effects on oxidative stress and inflammation—the impact of statins on ion currents and their tachycardia-induced alterations might also play a role in “upstream” treatment of AF with HMG-CoA reductase inhibitors.

Statins are highly effective and widely used lipid-lowering agents in clinical practice, that also display a number of pleiotropic properties beyond cholesterol lowering. Several trials have demonstrated that they reduce cardiovascular morbidity and mortality in both primary and secondary prevention. Atrial fibrillation (AF) and heart failure (HF) represent 2 world-wide epidemics. Recent evidence suggests that statins may have beneficial effects on cardiovascular outcomes in patients with HF, and specifically in the prevention of AF. The anti-arrhythmic mechanisms of statins regarding AF prevention in HF patients are not fully understood but are possibly related to their pleiotropic effects including anti-inflammatory, antioxidant, atrial remodeling attenuation, ion channel stabilization, and autonomic nervous system regulation.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice representing a major health hazard. Owing to relative inefficacy and side effects of classic antiarrhythmic drugs, current interest has shifted to treatments that target AF substrate. Accumulating evidence suggests that there is a link between oxidative processes and AF. In atrial myocardium during AF, there is substantial oxidative damage that may contribute to atrial remodeling. Several pathophysiological changes that possibly associated with increased oxidative stress in AF have been proposed. These include changes in gene transcriptional profiles and mitochondrial DNA, increased activity of enzymes such as NAD(P)H oxidase and xanthine oxidase, inflammatory processes, activation of the renin–angiotensin system and others. Moreover, oxidative stress is involved in the pathophysiology of several predisposing factors and cardiovascular disorders that correspondingly associated with AF. Preliminary studies using dietary antioxidants such as vitamin C have shown promising results. More evidence has been obtained from studies examining agents with pleiotropic effects, including antioxidant, such as inhibitors of the renin–angiotensin system, statins, corticosteroids and carvedilol. Further investigations are needed in order to elucidate the impact of oxidative stress on atrial remodeling. The clarification of these processes in the setting of AF may lead to the development of novel therapeutic strategies.