Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.
Level 2 - randomized trial
Large multicenter double-blind randomized controlled trial
PubMed 33190147 · doi:10.1001/jama.2020.22258
What was done
In a double-blind multicenter trial across 675 academic and community hospitals in 22 countries, 13078 statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low HDL-C were randomized to receive either 4 g/d of an EPA/DHA carboxylic acid formulation (omega-3 CA, n = 6539) or corn oil comparator (n = 6539). The primary efficacy endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.
What was found
The trial was halted prematurely for futility after 1384 primary events occurred out of a planned 1600. Ascertainment of primary endpoint status was completed in 12633 patients (96.6%). The primary endpoint occurred in 785 patients (12.0%) in the omega-3 CA group versus 795 (12.2%) in the corn oil group (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). Gastrointestinal adverse events occurred in 24.7% of omega-3 CA patients versus 14.7% of corn oil patients.
Why it matters
This trial shows that adding a high-dose combined EPA and DHA carboxylic acid formulation to standard background therapy provides no cardiovascular risk reduction in high-risk patients with atherogenic dyslipidemia.
Limits
The trial was stopped early for futility, reducing total accrued events. The study evaluated a combined EPA and DHA carboxylic acid formulation, so results cannot be directly extrapolated to other formulations such as purified EPA alone.
Cited by
- supports The STRENGTH trial testing 4 grams daily of omega-3 carboxylic acids (Epanova) was stopped early due to lack of clinical cardiovascular benefit.