No CV benefit from omega 3 in high-risk patients

Results from the STRENGTH trial did not indicate any primary prevention benefit of high-dose omega-3 in patients with high cardiovascular risk. There was no significant difference versus placebo for the composite outcome of major adverse cardiovascular events in this large randomised controlled trial [1].

Findings from the STRENGTH trial (NCT02104817) were presented by Prof. Michael Lincoff (Cleveland Clinic, USA), and were simultaneously published in JAMA [1,2]. The goal of the placebo-controlled STRENGTH trial was to evaluate the combined omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in patients with dyslipidaemia and high cardiovascular risk. The primary endpoint was a composite of cardiovascular death, non-fatal heart attack, non-fatal stroke, coronary artery revascularisation, and hospitalisation for unstable angina.

A total of 13,078 patients were randomised to receive daily supplementation with 4 g omega-3 fatty acids (n=6,539) or corn oil as placebo (n=6,539) in addition to usual background therapies, including statins. The mean age of the participants was 63 years, 35% were female, and 70% had diabetes. Median follow-up was 42 months.

Prof. Lincoff explained that the trial was terminated early for futility after an interim analysis. EPA/DHA did not reduce the incidence of major adverse cardiovascular events, despite a 269% increase in plasma EPA levels. The primary outcome occurred in 12.0% of the experimental group versus 12.2% of the placebo group (HR 0.99; 95% CI 0.90–1.09; P=0.84) (see Table for components). Gastrointestinal adverse events were seen in 24.7% in the EPA/DHA group versus 14.7% in the placebo group (P<0.001). Atrial fibrillation (AF) was observed in 2.2% and 1.3%, respectively. Prof. Lincoff said, “The STRENGTH trial showed a 67% increase in AF in the omega-3 treatment group, indicating that there is some uncertainty whether there is net benefit or harm with administration of any omega-3 fatty acid formulation. Given that 2 large clinical trials have now demonstrated a greater incident rate of AF with high-dose omega-3 fatty acid administration, this observation requires further study.”

Table: Results for the primary endpoint, its components, and all-cause death in the STRENGTH trial [1]



 

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      1. Lincoff AM, et al. STRENGTH Trial: Cardiovascular Outcomes With Omega-3 Carboxylic Acids (Epanova) in Patients With High Vascular Risk and Atherogenic Dyslipidemia. LBS.08, AHA Scientific Sessions 2020, 13–17 Nov.
      2. Nicholls SJ, et al. JAMA. 2020;324(22)2268-80.

Posted on 17 February 202125 March 2024