Upstream therapies to prevent atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia in the western world. It is associated with increased morbidity and mortality and decreased quality of life. The absence of a clear benefit of a rhythm-control strategy over a rate-control strategy observed in recent trials may be due to the fact that none of the available membrane-acting antiarrhythmics is entirely satisfactory. In addition, ablative therapy is available only for a small number of patients. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed ‘upstream’ of the electrical aspects of AF, towards the underlying anatomical substrate (atrial remodelling), have emerged as potential new pharmacological therapies. Potential upstream therapies for AF comprise a variety of agents such as those targeting the renin–angiotensin system [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)], statins, steroids, and N-3 polyunsaturated fatty acids. On the basis of suggestive experimental data, early phase clinical studies have been conducted and have provided exciting information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In some of these groups, such as patients with hypertension or heart failure, data may be considered to be sufficient to support the use of ACEI or ARB, at least in combination with membrane-acting antiarrhythmics. However, in most clinical settings examined, the evidence appears to be insufficient to drive changes in therapy management, and additional data from large-scale, randomized, double-blind, placebo-controlled trials with adequately defined endpoints are still needed. Numerous such trials are ongoing, reflecting the intense scientific interest in this field. The data derived from these trials may add to our understanding of the complex mechanisms that lead to AF and its maintenance, and may provide the necessary substantive evidence clarifying the benefit-to-risk ratio of these new therapeutic approaches.