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Omega-3s humbled by corn oil placebo in two trials

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Low-dose omega-3 fatty acids offered no cardiovascular benefit over corn oil placebo in two randomised trials of high-risk patients, resurfacing old questions about why REDUCE-IT managed a positive result with icosapent ethyl (Vascepa), writes Nicole Lou for MedPage Today.

In the STRENGTH trial, prescription omega-3 carboxylic acids (Epanova), a mix of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), didn’t lower cardiovascular events versus placebo in people with high triglycerides but did increase new-onset atrial fibrillation (Afib).

New-onset Afib had also been shown to be elevated with icosapent ethyl in the REDUCE-IT trial, as first reported in 2018.

In that trial, the prescription fish oil product (containing 4 g pure EPA) reduced cardiovascular events more than mineral oil placebo did in statin-treated people with high triglycerides. Supplements used in prior trials (for example, VITAL, ASCEND) had failed to show such a benefit, MedPage Today continues.

In OMEMI, a 1.8-g supplement combining EPA and DHA also failed to improve cardiovascular event rates, this time among elderly MI survivors in Norway. Again, there was a signal of more new-onset Afib among omega-3 fatty acid recipients.

Presentation of STRENGTH and OMEMI at this year’s virtual meeting of the American Heart Association left some questioning the safety of omega-3 fatty acid supplements and calling for another trial on icosapent ethyl.

Read the rest of this long and strong story on MedPage Today. See the link below.

 

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

JAMA Network. Published on 15 November 2020

Authors

Stephen J Nicholls, A Michael Lincoff, Michelle Garcia, Dianna Bash, Christie M Ballantyne, Philip J Barter, Michael H Davidson, John J Kastelein, Wolfgang Koenig, Darren K McGuire, Dariush Mozaffarian, Paul M Ridker, Kausik K Ray, Brian G Katona, Anders Himmelmann, Larrve E Loss, Martin Rensfeldt, Borbjorn Lundstrom, Rahul Agrawal, Venu Menon, Kathy Wolski and Steven E Nissen.

Affiliations include Monash University, Cleveland Clinic, University of Chicago and Baylor College of Medicine in the US, University of New South Wales, Academic Medical Center in Amsterdam, Technische Universität München and the University of Ulm in Germany, University of Texas, Tufts University and Harvard Medical School in Boston, Imperial College of London and AstraZeneca BioPharmaceuticals

Key points

Question: In statin-treated patients with high cardiovascular risk, high triglycerides, and low HDL cholesterol levels, does adding a carboxylic acid formulation of omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) to background therapy improve cardiovascular outcomes?

Findings: In this randomised clinical trial of 13 078 patients that was stopped early, daily supplementation with omega-3 fatty acids, compared with corn oil, resulted in no significant difference in a composite outcome of major adverse cardiovascular events (hazard ratio, 0.99)

Meaning: These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in patients with high cardiovascular risk.

Abstract

It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk.

Objective

To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk.

Design, setting and participants

A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa.

Interventions

Participants were randomised to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins.

Main outcomes and measures

The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalisation.

Results

When 1384 patients had experienced a primary end point event (of a planned 1,600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator.

Among the 13,078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status.

The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil–treated patients (14.7%).

Conclusions and relevance

Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events.

These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients.

 

MedPage Today story: Omega-3s Humbled by Corn Oil Placebo in Two Trials — Implications for REDUCE-IT’s icosapent ethyl unclear

 

JAMA Network article. 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

 


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