OMEGA 3 SAVES HEART: heart attacks reduced by 28%, MACE cardiovascular events reduced by 25% on over 33,000 subjects, data published New England JM

Two major studies presented at the American Heart Association Scientific Sessions 2018 and published in the prestigious New England Journal of Medicine confirm the benefits of marine-derived polyunsaturated fatty acids in the primary prevention of myocardial infarction and in preventing serious cardiovascular events in patients with high triglycerides

 In brief:

• Two new large-scale intervention studies involving over 33,000 people confirm the effectiveness of Omega-3s in protecting heart and cardiovascular health.
• In men over 50 and women over 55 without a history of cardiovascular disease, Omega-3 supplementation reduces the risk of myocardial infarction by 28%, fatal heart attacks by 50%, and coronary heart disease by 17%.
• In patients with high triglycerides, taking Omega-3 reduces the risk of myocardial infarction by 31%, stroke by 28%, cardiovascular death by 20%, and all-cause mortality by 13%.
• Experts say: “The greatest benefits from Omega-3 supplements were seen in those who had a low fish intake”.
• These striking results silence doubts raised by some recent meta-analyses on Omega-3 studies.

The association of Omega-3 fatty acids with cardiovascular health has been known for over forty years, and thousands of studies over the decades have accumulated a considerable amount of data supporting the hypothesis that they protect the heart and arteries. The European Food Safety Authority (EFSA) recommends consuming at least 250 mg per day of Omega-3 EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) to support proper heart function. New confirmations of the effectiveness of Omega-3 in protecting cardiovascular health come from the 2018 Scientific Sessions of the American Heart Association held in Chicago (Illinois, USA). These are based on results from two independent large-scale intervention studies.

The first, named REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial), confirms the usefulness of taking adequate doses of Omega-3 to reduce the risk of serious cardiovascular events when living with elevated triglyceride levels. Its results silence doubts raised by recent reviews of randomized controlled Omega-3 studies, confirming the importance of using a sufficient daily dose of Omega-3 (which in several studies was below the quantities needed to observe a significant effect) and reserving Omega-3 treatment for patients who can truly benefit due to their cardiovascular risk (in this case, elevated triglyceride levels). The second study, VITAL (VITamin D and OmegA-3 TriaL), instead highlights the effectiveness of Omega-3 in the primary prevention of myocardial infarction, regardless of predisposing risk factors.

Experts’ comments

“The study yielded very positive results both in terms of primary endpoints and major secondary endpoints,” said Deepak L. Bhatt, lead author of the REDUCE-IT study. “The greatest benefits from Omega-3 supplements were seen in those who ate little fish,” explained JoAnn E. Manson, principal author of the VITAL study. “We believe the VITAL study did not show any clear reason why those already taking fish oil supplements should stop,” Manson added. “And for those who seem likely to benefit—in particular, in terms of reduced heart attacks with Omega-3s, for those who eat little fish—we think it is reasonable to discuss with their doctor the possibility of taking these supplements.”  “The results align with the recommendations soon to be published as guidelines by the International Society for the Study of Fatty Acids and Lipids (ISSFAL), the scientific society dedicated to Omega-3 at an international level,” explains Clemens von Schacky, cardiologist at Ludwig Maximilian University of Munich (Germany) and a world expert on the relationship between Omega-3 and cardiovascular diseases. 

According to von Schacky, a key parameter to measure in this type of study is the so-called Omega-3 Index, an indicator of the amount of EPA and DHA relative to total fatty acids in the membranes of red blood cells, which should be measured before and during trials. “Otherwise, it is unclear what happened,” von Schacky explains. “In the VITAL study, omega-3s were measured in plasma rather than red blood cells, and the supplementation dose was not high enough to distinguish between intervention and placebo groups, as clearly stated by the authors. In REDUCE-IT, however, the EPA dose was sufficient to increase blood EPA levels nearly sixfold—clearly enough to differentiate intervention from control groups. Naturally, measuring the true Omega-3 Index would have provided a clearer picture.” This, explains the expert, is why the REDUCE-IT study showed clinically relevant effects more distinctly in both primary and secondary endpoints.

REDUCE-IT – the study

REDUCE-IT is a randomized, double-blind, placebo-controlled clinical trial (meaning the drug’s effect was compared to a placebo, participants were randomly assigned to groups, and neither participants nor researchers knew who received the drug or placebo). Participants had elevated triglyceride levels (between 150 and 499 mg/dl), controlled LDL cholesterol levels (between 41 and 100 mg/dl) due to statin therapy, and either a previous cardiovascular event or diabetes diagnosis plus at least one other cardiovascular risk factor. The primary outcome was the incidence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. Presented in Chicago on Saturday, November 10, and simultaneously published in the prestigious New England Journal of Medicine, the study involved 8,179 patients (average age 64, 29% women) recruited from 473 centers across 11 countries; average triglyceride and cholesterol levels were 216 and 75 mg/dl respectively, and 71% of participants were on cardiovascular risk reduction treatment. Each patient took 4 grams daily of Omega-3 EPA or a placebo, and their health status was monitored for an average of 4.5 years. The study showed that taking high doses of Omega-3 significantly reduces the risk of cardiovascular events in patients at risk due to high triglycerides. As previously announced last September by Amarin Corporation plc, the company producing the Omega-3 based drug tested in the study, the overall reduction in cardiovascular deaths, nonfatal myocardial infarctions and strokes, coronary revascularization or unstable angina requiring hospitalization was 25%. The Chicago event was the occasion to present more detailed results:

• During the first year of treatment, Omega-3 therapy led to an average reduction in triglyceride levels of 39 mg/dl, compared to an increase of 4.5 mg/dl in the control group;
• Omega-3s were effective regardless of triglyceride levels at the start of the study;
• With Omega-3s, the overall risk of heart attack, stroke, or cardiovascular death decreases by 26%;
• Omega-3s reduce the risk of nonfatal heart attack or stroke and all-cause mortality by 23%;
• Omega-3 intake reduces the risk of fatal or nonfatal myocardial infarction by 31%, fatal or nonfatal stroke by 28%, urgent or emergent revascularization by 35%, unstable angina or hospitalization by 32%, cardiovascular death by 20%, and all-cause mortality by 13%;
• Adverse effects were similar between groups. Bleeding (observed in 2.7% of patients treated with Omega-3 and 2.1% of those on placebo) was never fatal, and Omega-3 use did not increase the incidence of hemorrhagic stroke. Other side effects included diarrhea and anemia (more frequent in the control group) and constipation, peripheral edema, and atrial fibrillation (more frequent with Omega-3 use); hospitalizations for atrial fibrillation or flutter were more frequent among patients treated with Omega-3, but according to Bhatt this would be concerning if stroke risk were increased, while it was instead reduced by 28%.

VITAL – the study

VITAL is also a randomized, double-blind, placebo-controlled clinical trial presented in Chicago on November 10 and simultaneously published in the New England Journal of Medicine. In this study, the 25,871 participants (men and women with minimum ages of 50 and 55, respectively) did not have significant cardiovascular risk and no history of prior cardiovascular disease. Thus, the effectiveness of Omega-3s was tested in terms of primary prevention, i.e., in healthy individuals. Omega-3 treatment involved taking 1 g daily of fish oil containing 840 mg EPA (460 mg) + DHA (380 mg). The average treatment duration was 5.3 years. The primary endpoint was the incidence of major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), while secondary endpoints included the incidence of each cardiovascular event considered. The results showed a 28% reduction in myocardial infarction risk, a 50% reduction in fatal heart attacks, and a 17% reduction in coronary heart disease. Among participants who ate little fish, the reduction in heart attacks alone was 40%, while the broader reduction in cardiovascular events was 19%. 

Sources:

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1812792

https://www.nejm.org/doi/full/10.1056/NEJMoa1811403  

What are Omega-3s?

Essential fatty acids, Omega-3s are molecules indispensable for the proper functioning of the body that must be obtained through diet. Plant sources—such as walnuts—provide alpha-linolenic acid (ALA), while animal sources—such as salmon, mackerel, microalgae, and fish oil—provide eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the Omega-3s best utilized by the body and clinically the most important because they are associated with reduced inflammation and lower risk of chronic diseases. Moreover, EPA and especially DHA are particularly abundant in the brain, where they contribute to cognitive abilities and behavioral regulation, and DHA intake during pregnancy is recommended to support proper development of the baby's nervous system and vision.

Who is U.G.A. Nutraceuticals? U.G.A. Nutraceuticals, a member of GOED Omega-3, is one of the first Italian companies to start, since 2005, formulating, producing, and distributing highly purified Omega-3 supplements with quality certified by independent laboratories. Naturalness and transparency are the core values of U.G.A. Nutraceuticals, translated into a true corporate mission: to make Omega-3 dietary supplements accessible to everyone. Today, U.G.A. Nutraceuticals offers a wide range of products certified by sustainable fishing Friend of the Sea.