omacor and Arrhythmias--Cardiac

Safe pharmacotherapy and prevention of arrhythmia is an urgent problem of modern cardiology. Essential micronutrients such as omega-3 polyunsaturated fatty acids (-3 PUF-) significantly contribute to the metabolic processes in cardiomyocytes and cardiac conduction system. This article presents a systematic analysis of anti-arrhythmic effects of omega-3 PUFA and of standardized ethyl esters of omega-3 PUFA. The currently available data indicate two fundamentally different molecular mechanisms of anti-arrhythmic effects: "slow" and "fast" types. Formulation of fundamental prospects of bioinformatic studies of molecular effects of anti-arrhythmic action of omega-3 PUF-s is presented.

Topics: Arachidonic Acid; Arrhythmias, Cardiac; Biotransformation; Cardiovascular Agents; Clinical Trials as Topic; Cytochromes; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Heart Conduction System; Humans; Ion Channels; Micronutrients; Myocytes, Cardiac; Receptors, Eicosanoid; Receptors, Prostaglandin

Despite progress made in post-myocardial infarction (MI) revascularization and background therapy for the failing heart, the prevention of adverse cardiac remodeling associated with severe rhythm disorders remains an important drug target. Part of the remodeling can be counteracted by modulating the activity of ion channels and exchangers by omega-3 acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the GISSI-Prevenzione and GISSI-HF trials, omega-3 fatty acids were administered as ethyl esters (Omacor Solvay Pharmaceuticals) and not as triglycerides present in fish oil. Ethyl esters result in a sustained intestinal absorption of EPA and DHA and require various purification steps during production, thereby minimizing the content of environmental toxins. Also the rather high (38%) DHA content of Omacor should not be ignored since in rats with low dose intake of omega-3 acids, DHA but not EPA inhibited ischemia-induced arrhythmias. In patients on multiple tablets, 840 mg EPA+DHA in one capsule is preferred to increase compliance. It is not justified to refer to Omacor as "n-3 polyunsaturated fatty acid supplementation" or even "fish oil" and, based on controlled clinical trials, there is no evidence that fish oil could be a substitute of Omacor. To avoid further confusion, guidelines should be precise and refer to the medication, eg, as in NICE guideline CG48: "Omega-3-acid ethyl esters treatment licensed for secondary prevention post-MI." The anti-arrhythmogenic action of Omacor should be seen in the context of implantable cardioverter-defibrillator trials (DINAMIT, IRIS) where non-sudden death was increased and total mortality unaltered. However, Omacor administered in the GISSI-HF trial reduced the incidence of severe arrhythmic events and mortality. Also in the GISSI-Prevenzione trial, arrhythmic death and mortality were reduced. At higher dosages (daily, 3-4 g) Omacor exhibits more pronounced cardiovascular benefits and, as a licensed indication, improves hypertriglyceridemia and related lipid parameters.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Diseases; Clinical Trials as Topic; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Heart Failure; Humans; Hypertriglyceridemia; Hypoglycemic Agents; Medication Adherence; Myocardial Infarction