By Matey Juric; Roger S. Blumenthal, MD; Martha Gulati, MD
Very high triglycerides in the blood, known as hypertriglyceridemia, increase the risk of atherosclerotic cardiovascular disease (ASCVD) due to “hardening of the arteries.” ASCVD is the result of a buildup of plaque in blood vessels and
includes conditions such as coronary artery disease, cerebrovascular disease, and peripheral artery disease. Common treatment strategies often include lifestyle improvements, diabetes management, as well as statin therapy.
Recent evidence suggests that high-dose eicosapentaenoic acid (EPA), an omega-3 fatty acid, when given in another form called icosapent ethyl (IPE) along with statin therapy may greatly reduce the health risks associated with ASCVD. Omega-3 fatty acids
are known to have effects on inflammation, oxidation, stability of cell membranes and other conditions. However, among different omega-3 fatty acids, effects may differ. A recent editorial in the Journal of the American Medical Association discusses
the findings of four studies (“Effects of Omega-3 Fatty Acids on Major Adverse Cardiovascular Events - What Matters Most: the Drug, the Dose, or the Placebo?”
Nov. 15).
In the Japan EPA Lipid Intervention Study (JELIS), which involved over 18,000 patients, results showed about a 20% risk reduction in ASCVD for patients given EPA along with statin therapy, compared with a control group that received statin therapy
alone. In another trial called REDUCE-IT, patients already receiving statin therapy were also given either a prescription of high-dose EPA in the form of IPE, known as Vascepa, or a placebo. The results showed a decrease in nonfatal heart attack,
stroke, cardiovascular death, and angina (chest pain) by 25% in the IPE group over five years of follow-up with participants of the study, when compared with the placebo group.
EVAPORATE, a trial conducted to determine what effects Vascepa, the prescription medication that contains only IPE, may have on atherosclerosis showed similar results. In the study, 80 patients between 30- to 85-years-old who had pre-existing coronary
atherosclerosis and were already on statin therapy were split into two groups — one group received IPE and the other a placebo. The group receiving statin therapy along with IPE had a 17% reduction in plaque buildup compared with the placebo
group.
Although these results offer some promise, a study published in the Journal of the American Medical Association called the STRENGTH
trial looked at the risk that remains even after statin therapy in patients with high cardiovascular risk and very high triglycerides. However, this trial used a different form of EPA and docosahexaenoic acid (DHA), another omega-3 fatty acid. Both were
in their carboxylic acid form. Additionally, instead of using Vascepa, the STRENGTH study used Epanova, also a prescription medication, but it contains both EPA and DHA. Unlike the previous studies, this one was stopped due to lack of benefit.
Thus a major question arises, why did the STRENGTH study not have the same results as some of the others, such as REDUCE-IT? The editorial writers suggest that one reason may be that REDUCE-IT used a specific IPE form (Vascepa), while STRENGTH used a
mixture of EPA and DHA (Epanova). Additionally, it was found that the levels of EPA in the blood were not consistent across the two trials, with REDUCE-IT seeing a larger increase in EPA compared with STRENGTH (4-fold vs. nearly 3-fold increase).
It is possible that having a specific form of EPA may impact the way the fatty acid spreads throughout the body. Another potential concern mentioned in the editorial was that different placebos were used in the two studies, and this may have caused different
outcomes. Nevertheless, STRENGTH provides strong evidence that when you mix omega-3 fatty acids, risks associated with ASCVD are not reduced.
Despite the outcome of the STRENGTH study, finding that IPE has potential to lower the risk of ASCVD appears to be a breakthrough due to the success of the JELIS, REDUCE-IT and EVAPORATE studies, according to the editorial. However, without additional
trials that look at some of the concerns brought up by the differences in results, the authors write that future American College of Cardiology/American Heart Association clinical guidelines may not give the highest level of endorsement, which is
used when substantial evidence shows that a treatment option has a clear benefit.
Matey Juric is a premedical student at Drexel University. Roger S. Blumenthal, MD, FACC, is Director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. Martha Gulati, MD, FACC, is the Editor-in-Chief of CardioSmart.
Visit CardioSmart.org/VHTG to learn more.