Effects of n-3 Fatty Acid Supplements in Elderly Patients after Myocardial Infarction: A Randomized Controlled Trial.

Circulation

Nov 2020

DOI: 10.1161/CIRCULATIONAHA.120.052209

Citations:190

Influential Citations:12

Interventional (Human) Studies

Enhanced Details

Methods

Multicenter, randomized, double-blind, placebo-controlled trial (OMEMI). Participants: elderly adults aged 70–82 years with a recent acute myocardial infarction (2–8 weeks prior). 1027 randomized at 4 centers in Norway; follow-up 24 months; analyses by intention-to-treat and per-protocol.

Intervention

1.8 g n-3 polyunsaturated fatty acids daily (930 mg EPA + 660 mg DHA), taken as 3 capsules once daily for 24 months.

Results

No reduction in the primary composite outcome of major adverse cardiovascular events or death with omega-3 supplementation vs placebo over 2 years (HR 1.07; 95% CI 0.82–1.40; P=0.62). All-cause mortality similar (HR 1.01; 95% CI 0.60–1.71; P=0.97). New-onset atrial fibrillation was higher in the omega-3 group (7.2% vs 4.0%; HR 1.84; 95% CI 0.98–3.44; P=0.06). Major bleeding did not differ (10.7% vs 11.0%; P=0.87). Serum EPA increased by 87% and DHA by 16% in the omega-3 group, confirming adherence. Conclusion: In elderly patients after a recent MI, daily 1.8 g of n-3 PUFA for 2 years did not reduce cardiovascular events or death; potential AF risk observed; routine omega-3 supplementation for secondary prevention in this population is not supported by this trial.

Limitations

Low enrollment rate (26% of screened); potentially underpowered to detect the prespecified effect due to lower-than-expected event rate; elderly population with relatively high baseline omega-3 intake may limit generalizability; protocol amendment adding heart failure hospitalization to the primary endpoint; some cod liver oil use allowed.

Abstract

Background: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after MI, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. Methods: The OMega-3 fatty acids in Elderly with Myocardial Infarction (OMEMI) trial is an investigator-initiated, multi-center, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg EPA and 660 mg DHA) versus placebo (corn oil) daily to standard of care in 70-82 years old patients with recent (2-8 weeks) AMI. The primary endpoint was a composite of non-fatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after two years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. Results: In total, 1,027 patients were randomized. Follow-up data were available for 1,014 patients who were included in the intention-to-treat analysis. Mean ± SD age was 75±3.6 years, 294 (29%) were female and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA vs 102 (20.0%) on placebo (HR 1.08 [95%CI 0.82-1.41], p=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA vs 15 (4.0%) on placebo (1.84 [0.98 -3.45], p=0.06). Median changes in EPA and DHA were +87% and +16% for n-3 PUFA vs -13% and -8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (p=0.87). Similar results were found in per-protocol analysis (n=893). Conclusions: We could not detect reduction in clinical events in our elderly patients with a recent AMI, treated with 1.8 g n-3 PUFAs daily for 2 years. Clinical Trial Registration: OMEMI Study; URL: https://clinicaltrials.gov Unique Identifier: NCT01841944. show less