New aspects of the mechanism of action of omega-3 fatty acids in atherothrombotic cardiovascular disease
Clinical and basic research shows that eicosapentaenoic acid (EPA) plays a beneficial role as a supplement to statin treatment to slow down the development and progression of atherosclerotic disease.
Omega-3 fatty acids, such as EPA and docosahexaenoic acid (DHA), have different effects on cell membrane structure, lipid dynamics and oxidative stress in the lipid membrane. A comparison of pharmacological treatments such as niacin, which reduces triglyceride (TG) levels, with the omega-3 fatty acid, EPA, shows that the latter reduces levels of inflammatory markers, cholesterol crystal formation, endothelial dysfunction and oxidative modification of ApoB lipoproteins, as well as increasing HDL functionality.
Consumption of marine-origin long-chain omega-3 polyunsaturated fatty acids significantly reduces TG levels and the risk of cardiovascular morbidity and mortality. Published data on the efficacy of omega-3 fatty acids in atherosclerotic cardiovascular disease vary, as low doses of omega-3 fatty acids containing EPA and DHA (1 g/day) have not been shown to have any cardiovascular benefit.
In the lipid intervention trial carried out in Japan (JELIS), a dose of purified EPA (1.8 g/day) combined with statins was effective in reducing the risk of coronary events in hypercholesterolemic patients, compared to patients treated with statins alone. Furthermore, regression of the coronary atheroma plaque was observed by integrated backscatter intravascular ultrasound in patients treated with statins in combination with EPA (1.8 g/day and pitavastatin).
The REDUCE-IT trial was a double-blind, randomised placebo-controlled trial designed to study the effects of icosapent ethyl, a highly purified EPA ethyl ester, in reducing cardiovascular events. The main objective of the study was to determine whether treatment with EPA reduces ischaemic events in patients treated with statins, with high baseline fasting levels of TG and a high risk of clinical cardiovascular events. The results showed that in patients with high TG levels, despite the use of statins, the risk of ischaemic events, including cardiovascular death, was significantly lower among those receiving 2 g of icosapent ethyl twice daily compared to those receiving placebo.
Another double-blind, randomised, placebo-controlled trial, STRENGTH (trial to assess statin residual risk reduction with Epanova in high cardiovascular risk) is currently underway and in which high-risk patients with high TG levels are treated with 4 g/day of EPA and DHA-free fatty acids. The results are to be published in 2020.
In the near future, current clinical trials will provide additional information on the role of omega-3 fatty acids in reducing residual cardiovascular risk and the progress of coronary atherosclerosis in subjects with well controlled LDL-C but high levels of TG.