The administration of omega-3 carboxylic acid (CA) at a high dose did not reduce the incidence of major adverse cardiovascular events compared with placebo, according to the results of the STRENGTH trial. This lack of benefit occurred despite a nearly 300% increase in plasma EPA levels.
Results were presented by A. Michael Lincoff, MD, vice chairman for Research of the Department of Cardiovascular Medicine and an interventional cardiologist in the Heart, Vascular & Thoracic Institute at the Cleveland Clinic, as part of a news briefing at the American Heart Association Scientific Sessions 2020.
The cardiovascular benefits of administration of omega-3 fatty acids remains incompletely defined, Dr. Lincoff explained. Omega-3 CA does not require pancreatic lipase for absorption and, thus, has enhanced bioavailability to achieve higher and more reliable blood levels.
To test omega-3 CA, STRENGTH enrolled patients were statin-treated and had or were at high risk for cardiovascular disease with triglycerides ranging from 180 mg/dL to 500 mg/dL and HDL less than 42 mg/dL for men and 47 mg/dL for women. The primary endpoint was cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
In the trial, 13,078 patients from 676 sites in 22 countries were randomly assigned to omega-3 CA (EPA + DHA) 4 g daily or identical corn-oil placebo. Median follow-up was 42.0 months. Patients were randomized from October 2014 to June 2017. In January 2020, the Data Monitoring Committee recommended stopping the trial for futility after reviewing 1,384 primary endpoints.
With a median follow-up of about three years, 1,580 patients had experienced at least one cardiac event.
For patients assigned to omega-3 CA triglyceride levels were reduced by 19% and hsCRP was reduced by 20% for patients. There were little differences in LDL or HDL between baseline and follow-up with administration of omega-3.
Plasma and red blood cell levels of EPA were increased between 268.8% and 298.6%, respectively. There were more modest increases in DHA for plasma and red blood cells (39.7% and 23.9%). Despite the biochemical effects, there was no difference in the primary outcome with treatment with omega-3 CA and placebo, with superimposable survival curves.
The major adverse effect of concern was atrial fibrillation, which was increased by about 70% with omega-3 CA (HR=1.69; 95% CI, 1.29 to 2.21).
“These findings, in the context of the increased risk of atrial fibrillation in this and other trials of omega-3 fatty acids, cast a question regarding whether or not there is a net benefit or harm with any omega-3 fatty acid preparation,” Dr. Lincoff concluded.