Adding omega 3 fatty acid to statins helped to reduce stroke risk by 36% in those with cardiovascular disease


Taking the triglyceride-lowering medication icosapent ethyl cut the risk of stroke by an additional 36% in people at increased risk of cardiovascular disease who already have their bad cholesterol levels under control using statin medications, according to preliminary research to be presented at the American Stroke Association’s International Stroke Conference 2021.

The virtual meeting is March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

“Icosapent ethyl is a new way to further reduce the risk of stroke in patients with atherosclerosis or who are at high risk of stroke, who have elevated triglyceride levels and are already taking statins,” said Deepak L. Bhatt, M.D., M.P.H., lead author of the study and executive director of interventional cardiovascular programs at the Brigham and Women’s Hospital Heart & Vascular Center in Boston.

Icosapent ethyl is a prescription medication that is a highly purified form of the omega-3 fatty acid eicosapentaenoic acid. “It is very different in terms of purity compared to omega-3 fatty acid supplements available over-the-counter, and these results do not apply to supplements,” said Bhatt, who is also professor of medicine at Harvard Medical School.

Icosapent ethyl was first approved in July 2012 by the U.S. Food and Drug Administration as an adjunct treatment to dietary changes to lower triglycerides in people with extremely high levels of triglycerides (higher than 500 mg/dL).

Triglycerides are fats from food that are carried in the blood; normal levels for an adult are below 150 mg/dL.

In late 2018, the REDUCE-IT trial, an 8,000-person multinational study, demonstrated that icosapent ethyl could benefit people with heart disease, diabetes or triglyceride levels above 150 mg/dL and whose LDL (bad) cholesterol levels were already under control using statin medication.

In the trial, adding icosapent ethyl (compared with a placebo) reduced the risk of serious cardiovascular events (heart attack, heart-related death, stroke, need for an artery-opening procedure or hospitalization for heart-related chest pain) by 25%.

In December 2019, the FDA approved icosapent ethyl as a secondary treatment to reduce the risk of cardiovascular events among adults with elevated triglyceride levels, and it is now recommended in some professional guidelines.

Icosapent ethyl is not included in the American Heart Association’s 2018 Cholesterol Guidelines that were published online prior to the availability of the REDUCE-IT primary results.

In the current analyses, REDUCE-IT Stroke, researchers performed an additional analysis of the impact of icosapent ethyl on stroke in the same 8,000 participants of the original REDUCE-IT trial. They found:

  • the risk of a first fatal or nonfatal ischemic stroke was reduced by 36% for patients treated with icosapent ethyl;
  • for every 1,000 patients treated with icosapent ethyl for 5 years, about 14 strokes were averted; and
  • the risk of a bleeding stroke was very low, and no difference was found among those taking icosapent ethyl.

“Know your triglyceride levels. If they are elevated, ask your doctor if you should be taking icosapent ethyl to further reduce your risk of heart attack and stroke,” Bhatt said.

“Your doctor may also recommend that you change your diet, exercise, lose weight if needed to lower your triglyceride levels, and may prescribe a statin medication if you need to lower your LDL cholesterol levels.”

“One study limitation is that icosapent ethyl may increase the risk of minor bleeding,” Bhatt added.

Co-authors are Gabriel Steg, M.D.; Michael Miller, M.D.; Eliot A. Brinton, M.D.; Terry A. Jacobson, M.D.; Steven B. Ketchum, Ph.D.; Rebecca A. Juliano, Ph.D.; Lixia Jiao, Ph.D.; Ralph T. Doyle Jr., B.A.; Craig Granowitz, M.D., Ph.D.; Jean-Claude Tardif, M.D.; John Gregson, Ph.D.; C. Michael Gibson, M.D.; Megan C. Leary, M.D.; and Christie M. Ballantyne, M.D. The author’s disclosures are listed in the abstract.

Funding: The study was funded by Amarin Pharma

Source: American Heart Association

arious heart diseases such as hypertensive heart disease, ischemic heart disease and valvular heart disease finally result in heart failure1. Despite extensive studies and drug development, heart failure is still a leading cause of death in the world. Many mechanisms of heart failure have been reported such as ischemia, abnormal calcium handling, cardiomyocyte death, increase of reactive oxygen species (ROS) and mitochondrial dysfunction2,3,4,5,6.

Recently, inflammation has been reported to be critically involved in the development of cardiac hypertrophy and heart failure4,5,7,8,9. Serum concentrations of pro-inflammatory cytokines such as TNFα, IL-1β and IL-6 as well as biomarkers such as CRP and galectin-3 have been reported to be elevated in patients with heart failure10,11, and their increases were attenuated by some therapeutic agents for heart failure such as angiotensin converting enzyme inhibitors and β blockers11.

Fatty acids (FAs) have three major biological roles such as an energy source, cellular membrane components and lipid mediators12. Considering that the heart beats every second, FAs are important as a source of sufficient energy and as a component of cellular membranes. Among lipid mediators, omega-3 FA and omega-6 FA have attracted much attention as sources of lipid mediators of inflammation7,13,14,15,16,17.

Under basal conditions, these FAs are mainly located at sn-2 position of phospholipids in a cellular membrane. Once inflammatory stresses are imposed on a tissue, activated phospholipase A2 (PLA2) hydrolyzes the sn-2 ester bond of membrane phospholipids, and releases free form FAs such as arachidonic acid (ARA) from omega-6 FAs, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from omega-3 FAs.

These free forms of FAs are modified by cyclooxygenase (COX)-2, 5-lipoxygenase (LOX) and 12/15-LOX, and are eventually turned into biological active lipid mediators14,15,16,17,18. It has been reported that ARA-derived metabolites are pro-inflammation, while EPA- and DHA-derived ones are pro-resolution13,14,15,16,17.

Some metabolites have been reported to play a critical role in the development of cardiac hypertrophy and heart failure by regulating inflammatory reaction19,20,21. Recently, clinical trials showed that omega-3 FA supplementation reduced cardiovascular events22,23,24,25,26, but the underlying molecular mechanisms remain unknown.

In this study, we examined whether omega-3 FA supplementation has any effects on the composition of FA in the heart and whether these changes have beneficial effects on cardiac function and remodeling.



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