Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality, the so-called AF burden. Despite significant progress in the understanding, the mechanisms and pathophysiology of AF treatments are often unsatisfactory. This in part may be related to the complexity of this arrhythmia, as well as its evolution overtime. Atrial fibrillation has many aetiologies and underlying causes. The anti-arrhythmic drugs (AADs) and interventions

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... at controlling AF should therefore be based on aetiology and associated conditions, rather than electrophysiological mechanisms. The current guideline in the management of AF in most part is based on safety and outcome. This review will discuss the approach to management, based on primary prevention of AF with the aim to target at risk factors, triggers, specific substrates related to aetiology rather than mechanisms. The development of new pharmacological agents and therapeutic strategies should consider not only evidence based, but also include patient-specific personalized context system biology and pharmacology; otherwise, we will continue to see moderate drug efficacy at best and negative results and outcomes.