Primary and secondary prevention of atrial fibrillation with statins and polyunsaturated fatty acids: review of evidence and clinical relevance

Atrial fibrillation (AF) is an increasingly common arrhythmia that now stands at epidemic proportion, with more than 2.3 million people affected in the USA and over 4.5 million people affected in Western Europe. AF is an expression of underlying heart disease and is increasingly associated with hypertension, congestive heart failure, and ischemic heart disease. It is also a progressive disease secondary to continuous structural remodeling of the atria, which relates to AF itself, to changes associated with aging and to progression of the underlying heart disease. Traditionally, AF has been addressed only after it has already presented with pharmacological and nonpharmacological therapies designed for rhythm or rate control (secondary prevention). Although secondary prevention is the most feasible approach at present, the concept of primary prevention of AF with therapies aimed at preventing the development of substrate and correcting the risk factors for AF has emerged as a strategy, which is likely to produce a larger effect in the general population. Recent experiments provided new insights into AF pathophysiology, which generated background for new mechanism-based therapies. Agents targeting inflammation, oxidative injury, atrial myocyte metabolism, extracellular matrix remodeling, and fibrosis have theoretical advantages as novel therapeutic strategies. In this respect, drugs that are not traditionally antiarrhythmic such as angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, statins, and omega-3 polyunsaturated fatty acids have shown an antiarrhythmic potential in addition to any treatment effect on the underlying disease. These agents are thought to have an advantage of targeting both the occurrence and progression of the substrate for AF, thus, providing primary and secondary prevention of the arrhythmia. Although first experimental and hypothesis-generating small clinical studies or retrospective analyses have been encouraging, several larger, properly designed, prospective trials have not confirmed earlier observations. This review provides a contemporary evidence-based insight into the possible preventative and reverse remodeling role of statins and polyunsaturated fatty acids in AF.