At highest plasma level, omega-3 fatty acids pose no heart health effect: STRENGTH trial
USA: Achieving higher plasma levels of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in patients treated with omega 3 fatty acids is associated with neither benefit nor harm in patients at high cardiovascular risk, finds a recent study.
The findings, published in the journal JAMA Cardiology, do not support the conception that achieving higher plasma levels of EPA through pharmacological means reduces adverse cardiovascular outcomes. Also, higher DHA levels were not associated with harm.
Trials that tested the cardiovascular effects of the administration of omega-3 fatty acids have yielded inconsistent results. Recently, the Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial (REDUCE-IT) showed a large reduction in cardiovascular events. The Long-term Outcomes Study to Assess Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia (STRENGTH) trial showed a neutral effect.
To get some clarity on the above ambiguity, Steven E. Nissen, Cleveland Clinic, Cleveland, Ohio, and colleagues conducted a secondary analysis of the STRENGTH trial with an objective to determine the association between plasma levels of EPA and DHA and cardiovascular outcomes in a trial of ω-3 fatty acids compared with corn oil placebo.
The double-blind, multicenter trial enrolled 13 078 patients at high cardiovascular risk with increased triglyceride levels and low levels of high-density lipoprotein cholesterol at 675 centers. Enrollment began from October 30, 2014, to June 14, 2017, and was terminated on January 8, 2020. 6539 (50%) were randomized to receive 4 g daily of ω-3 carboxylic acid (CA) and 6539 (50%) received an inert comparator, corn oil.
The primary prespecified end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. The primary outcome measure was the hazard ratio, adjusted for baseline characteristics, for patients treated with the ω-3 CA compared with corn oil for the top tertile of achieved EPA and DHA plasma levels 12 months after randomization.
Key findings include:
- ω-3 Fatty acid levels were available at both baseline and 12 months after randomization in 10 382 participants (5175 ω-3 CA patients [49.8%] and 5207 corn oil–treated patients [50.2%]; mean age, 62.5 years, 3588 [34.6%] were women, 9025 [86.9%] were White, and 7285 [70.2%] had type 2 diabetes).
- The median plasma levels at 12 months in ω-3 CA patients were 89 μg/mL for EPA and 91 μg/mL for DHA with top tertile levels of 151 μg/mL and 118 μg/mL, respectively.
- Compared with corn oil, the adjusted hazard ratios for the highest tertile of achieved plasma levels were 0.98 for EPA, and 1.02 for DHA.
- Sensitivity analyses based on changes in plasma and red blood cell levels of EPA and DHA and primary and secondary prevention subgroups showed similar results.
Nissen and the team concluded, "Among patients treated with ω-3 CA, the highest achieved tertiles of EPA and DHA were associated with neither benefit nor harm in patients at high cardiovascular risk."
Reference:
Nissen SE, Lincoff AM, Wolski K, et al. Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk: A Secondary Analysis of the STRENGTH Trial. JAMA Cardiol. 2021;6(8):910–917. doi:10.1001/jamacardio.2021.1157
