Abstract
Traditional anti-arrhythmic drugs are classified by the Vaughan-Williams classification scheme based on their mechanisms of action, which includes effects on receptors and/or ion channels. Some known anti-arrhythmic drugs do not perfectly fit into this classification scheme. Other medications/molecules with established non-anti-arrhythmic indications have shown anti-arrhythmic properties worth exploring. In this narrative review, we discuss the molecular mechanisms and evidence base for the anti-arrhythmic properties of traditional non-antiarrhythmic drugs such as inhibitors of the renin angiotensin system (RAS), statins and polyunsaturated fatty acids (PUFAs). In summary, RAS antagonists, statins and PUFAs are 'upstream target modulators' that appear to have anti-arrhythmic roles. RAS blockers prevent the downstream arrhythmogenic effects of angiotensin II - the main effector peptide of RAS - and the angiotensin type 1 receptor. Statins have pleiotropic effects including anti-inflammatory, immunomodulatory, modulation of autonomic nervous system, anti-proliferative and anti-oxidant actions which appear to underlie their anti-arrhythmic properties. PUFAs have the ability to alter ion channel function and prevent excessive accumulation of calcium ions in cardiac myocytes, which might explain their benefits in certain arrhythmic conditions. Clearly, whilst a number of anti-arrhythmic drugs exist, there is still a need for randomised trials to establish whether additional agents, including those already in clinical use, have significant anti-arrhythmic effects.