Omega-3 fatty acids on high of ordinary care didn’t cut back main cardiovascular occasions or demise in aged survivors of an acute myocardial infarction (MI) within the randomized OMEMI trial.
Along with the dearth of profit noticed at 2 years, there was a nonsignificant improve in new-onset atrial fibrillation in these taking 1.8 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) each day in contrast with a corn oil placebo.
“Our findings don’t assist omega-3 fatty acid preparations for secondary prevention in aged sufferers,” principal investigator Are A. Kalstad, MD, stated on the digital American Coronary heart Affiliation (AHA) 2020 Scientific Periods.
The findings, which had been revealed concurrently in Circulation, echo these from the STRENGTH trial reported in the identical late-breaking science session displaying no profit on cardiovascular occasion charges of a excessive dose mixture of EPA and DHA in a brand new branded product (Epanova, AstraZeneca).
The OMEMI outcomes, although, are notably impactful for the aged, who are sometimes shut out of medical trials and whose cardiovascular danger stays notably excessive, even with up to date secondary prevention.
Alberico L. Catapano, PhD, MD(HC), the discussant through the session tasked with decoding each trials, stated dose could have performed a job in immediately’s impartial outcomes in contrast with the REDUCE-IT trial, by which 4 g each day of EPA alone (icosapent ethyl, Vascepa, Amarin) minimize the relative danger for main cardiovascular occasions by 25% in sufferers at elevated cardiovascular danger.
The brand new knowledge are in step with a meta-analysis displaying a higher impact with greater vs decrease doses of omega-3 fatty acids, he stated. Latest research additionally point out EPA could behave in another way in stabilizing cell membranes and in including anti-inflammatory results than DHA.
Though each the STRENGTH and OMEMI trials used a corn oil placebo, a lot has been made a couple of potential damaging impact of a mineral oil placebo like that utilized by the REDUCE-IT investigators. Nevertheless, “all the data now we have is circumstantial to say that the placebo made a distinction for REDUCE-IT,” stated Catapano, from the College of Milano, Italy.
He additionally discarded the argument that REDUCE-IT could have enrolled sufferers with extra established coronary artery illness (CAD), as all the OMEMI sufferers had CAD.
Strong proof remains to be wanted to clarify why the outcomes are discordant, Catapano stated. “Actually the dose has been completely different and which may be, for my part, one of many seemingly explanations. There’s actually, although, one frequent outcome — an rising incidence of atrial fibrillation, albeit insignificant in OMEMI.”
The Omega-3 fatty acids in Aged with Myocardial Infarction (OMEMI) trial included 1027 sufferers, age 70 to 82 years, who skilled an acute MI 2 to eight weeks previous to being assigned to obtain both 1.8 g of omega-3 polyunsaturated fatty acids (930 mg EPA and 660 mg DHA; Pikasol, Orkla Well being) or matching corn oil placebo (56% linoleic acid, 32% oleic acid, 10% palmitic acid). The overall dose was divided into three capsules taken as soon as each day.
At baseline, the median age was 74 years, 29% of sufferers had been feminine, and all however two sufferers had been White. Roughly half had recognized earlier heart problems on the time of the index MI. Practically all had been taking statins (96%) and 86% had been additionally receiving antihypertensive medicines and twin antiplatelet remedy.
Kalstad identified that omega-3 dietary supplements or cod liver oil was utilized by 40% of sufferers and triglyceride ranges had been comparatively low, at 115.4 mg/dL within the omega-3 group and 107.4 mg/dL within the placebo group.
The investigators hypothesized that omega-3 fatty acids on high of ordinary care would scale back the first endpoint — a composite of nonfatal MI, unscheduled revascularization, stroke, coronary heart failure hospitalization, and all-cause demise — by 30% at 2 years.
Among the many 1014 sufferers with 2-year follow-up, nevertheless, the first consequence didn’t differ between the omega-3 and placebo teams (108 vs 102 occasions; hazard ratio [HR], 1.07; 95% CI, 0.82 – 1.40; P = .62).
Equally, there was no important impact on any of the person parts, together with demise (28 occasions in every group), or throughout 12 subgroups, together with age, triglyceride ranges, and prior omega-3 supplementation. The outcomes additionally remained impartial in per-protocol analyses.
For the prespecified secondary endpoint of new-onset atrial fibrillation, the investigators excluded 255 sufferers who skilled atrial fibrillation earlier than randomization, leaving 759 out there for evaluation.
Amongst these, there have been 28 new instances of atrial fibrillation within the omega-3 group and 15 within the management group (7.2% vs 4.0%; HR, 1.84; 95% CI, 0.98 – 3.44; P = .06).
Though the distinction was not statistically important and the affected person numbers had been small, “we can’t rule out potential hurt in rising the chance of atrial fibrillation,” Kalstad stated.
The first security endpoint of main bleeding was not considerably completely different between the omega-3 and management teams (10.7% vs 11.0%; P =.87), and no affected person discontinued the examine drug due to bleeding.
The commonest causes for stopping the examine drug had been hospitalization or intercurrent illness, problem swallowing the capsules, and nonspecific gastrointestinal signs.
Total, self-reported adherence was typically good at 88% in each teams, Kalstad stated. This was supported by an almost 100% improve from baseline in serum EPA ranges within the omega-3 group — albeit properly in need of the 386% improve in EPA at 1 yr in REDUCE-IT.
Particularly, the omega-3 group confirmed a median +87% change within the focus of EPA and a +16% change in DHA, whereas the placebo group modifications had been –13% and –8%, respectively, expressed as relative modifications from baseline, based on the paper.
Requested in regards to the potential for organic variations within the results of icosapent ethyl vs mixture omega-3 formulations and whether or not the achieved EPA ranges influenced medical outcomes, Kalstad stated the best way they measured serum fatty acids generated set factors that will not be straight comparable with different research. OMEMI individuals additionally appeared to start out out at greater baseline ranges than these in different research.
Nonetheless, “it is tempting to take a position on whether or not there’s kind of ‘candy spot’ for each cardiovascular results, advantages, and the potential hurt for atrial fibrillation,” Kalstad stated.
The work was supported by unrestricted grants from the Stein Erik Hagen Basis for Medical Coronary heart Analysis, the Olav Thons Basis, and the Tom Wilhelmsen Basis. Research medicine and placebo had been equipped by Orkla Well being. Catapano has obtained honoraria, lecture charges, or analysis grants from Sigma-Tau, Manarini, Kowa, Recordati, Eli Lilly, AstraZeneca, Mediolanum, Pfizer, Merck, Sanofi, Aegerion, Amgen, Genzyme, Bayer, Sanofi, Regeneron Daiichi-Sankyo, and Amarin.
American Coronary heart Affiliation (AHA) 2020 Scientific Periods. LBS4. Introduced November 15, 2020.
Circulation. Printed on-line November 15, 2020. Summary