The Mechanism of Action of Omega-3 Fatty Acids in Secondary Prevention Post-Myocardial Infarction

Nigel Harrison; Brihad Abhyankar

Disclosures

Curr Med Res Opin. 2005;21(1):95-100. 

In This Article

Mechanism of Action of Current Secondary Prevention Strategies

Secondary prevention post-MI has developed considerably in the past two decades, due in large part to extensive clinical trials of various medical interventions. The current recommended drug therapies for secondary prevention are reviewed very briefly below; they include the following agents:

  • Anti-platelet agents, particularly aspirin.

  • Beta-blockers.

  • Lipid-lowering drugs, particularly statins.

  • Angiotensin Converting Enzyme Inhibitors (ACE inhibitors).

Anti Platelet Agents

Aspirin prevents formation of platelet thromboxane A2, a substance that induces further platelet aggregation. As platelets have no nuclei and they are unable to generate new cyclo-oxygenase, enzyme inhibition lasts for the life of the cell (about 10 days). The most recent meta-analysis of the effects of antiplatelet therapy (almost exclusively aspirin) in controlled trials in secondary prevention has accumulated data from some 20 000 post-MI patients.[44] Therapy for a mean interval of 27 months was associated with a 25% reduction in risk of a vascular event.

Beta-Blockers

Beta-blockers can reduce the risk of an additional MI. There are several potential mechanisms for the benefit of beta-blockers for post-MI patients. Beta-blockers may be used for their antiarrhythmic properties. Blockade of sympathetic neuronal beta receptors leads to a reduction in systemic catecholamine release, thereby reducing heart rate, systolic arterial pressure, wall tension and contractility as well as reducing oxygen demand of the heart.[45]

Through these effects, infarct size is reduced, cardiac death reduced by 25%, reinfarction by 26% and sudden death by 30%.[45] It is recommended that beta-blockers should be initiated in all patients after MI infarction unless there is an absolute contraindication.[46,47]

ACE Inhibitors

A comprehensive review of ACE inhibitors after MI is provided by McMurray.[48] ACE inhibitors essentially act through antagonism of angiotensin II. The impressive results obtained with ACE inhibitors in the field of chronic heart failure prompted the investigation of their potential role in attenuating the degree of left ventricular dysfunction that results following acute MI. A series of large and well-conducted randomized studies (including SAVE,[49] AIRE,[50] GISSI-3,[51] TRACE[52]) demonstrated significant mortality benefits in patients admitted with acute MI. These trials provide evidence for the benefit, in terms of morbidity and particularly mortality, of ACE-inhibitor treatment in post-MI patients with either clinic ally evident heart failure or a degree of left ventricular dysfunction.

Lipid-Lowering Drugs

In the context of secondary prevention, the term 'lipidlowering drug' has been largely replaced by the statins. Trials such as 4S,[53] LIPID[54] and CARE[55] have established their role in secondary prevention.

While a comprehensive review of statins is beyond the scope of this article, it is accepted that the beneficial effects of statins are the result of their capacity to reduce plasma cholesterol levels. Statins have antiatherosclerotic effects that positively correlate with the percentage decrease in LDL cholesterol. In addition, they exert antiatherosclerotic effects independently of their hypo lipidaemic action. Statins have beneficial pleiotropic effects including effects on endothelial cell function, stability of the atherosclerotic plaque and effects on the inflammatory process within the plaque.[56] As a consequence, statins significantly reduce the incidence of coronary events, within both primary and secondary prevention and are the most effective hypolipidaemic compounds currently available.

Table 1 summarises the mechanisms of these therapies.

Addition of EPA + DHA Supplements to Current Standard Therapies

Omega-3 fatty acids have been evaluated in a large-scale trial and the evidence shows that this drug provides an additional benefit, over and above that provided by current treatment. An evidence-based approach would be to prescribe a pharmaceutical grade omega-3 fatty acid products such as Omacor.[57]

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