Omega-3 Fatty Acid Supplementation and Coronary Heart Disease Risks: A Meta-Analysis of Randomized Controlled Clinical Trials

Frontiers in Nutrition

Feb 2022

DOI: 10.3389/fnut.2022.809311

Citations:47

Influential Citations:2

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Adults (≥18 years) with high CHD risk, diagnosed CHD, or acute MI; randomized controlled trials (RCTs) with varying blinding (open-label to quadruple-blind) in multicenter or single-center designs; 14 RCTs comprising 135,291 participants.

Intervention

Omega-3 fatty acids (EPA and DHA) given as daily oral supplementation; regimens ranged from about 0.4 g/day to 4.0 g/day; moderate-dose (0.8–1.2 g/day) showed the strongest cardiovascular risk reductions; treatment durations varied from roughly 1 to 7.4 years.

Results

Omega-3 fatty acid supplementation reduced major adverse cardiovascular events (MACE) by 5% (RR 0.95, 95% CI 0.91–0.99), cardiovascular death by 6% (RR 0.94, 95% CI 0.89–0.99), and myocardial infarction by 14% (RR 0.86, 95% CI 0.79–0.93). No significant effect on all-cause death, stroke, or revascularization overall. In subgroups: acute MI reduces MACE and CV death; CHD reduces MI and stroke; high-risk CHD reduces MI. Moderate-dose regimens (0.8–1.2 g/day) confer the greatest benefits; lower or higher doses show less or no benefit. Diabetes status and sex did not significantly modify MACE risk. Conclusion: omega-3 fatty acids can reduce cardiovascular risk in CHD contexts, especially at moderate doses; high-dose regimens may carry atrial fibrillation risk and offer no additional benefit.

Limitations

Subgroup analyses had small sample sizes; most trials conducted in Western populations with limited data on Asians; potential confounding from concurrent secondary prevention therapies; heterogeneity in trial designs and outcome definitions; possible increased risk of atrial fibrillation with high-dose omega-3; more large, diverse RCTs are needed.

Abstract

Background The clinical benefits of omega-3 fatty acids (FAs) supplementation in preventing and treating coronary heart disease (CHD) remain controversial. Therefore, this study aimed to investigate the clinical benefits of omega-3 FA supplementation, with special attention given to specific subgroups. Methods Randomized controlled trials (RCTs) that compared the effects of omega-3 FA supplementation for CHD vs. a control group and including at least 1,000 patients were eligible for the inclusion in this meta-analysis. The relative risk (RR) of all-cause death, major adverse cardiovascular events (MACEs), cardiovascular death, myocardial infarction (MI), stroke, and revascularization were estimated. We analyzed the association between cardiovascular risk and omega-3 FA supplementation in the total subjects. We focused on the cardiovascular risk compared to omega-3 FA in subgroups with different development stages of CHD, omega-3 FA supplementation application dose, diabetes, and sex. PROSPERO Registration Number: CRD42021282459. Results This meta-analysis included 14 clinical RCTs, including 1,35,291 subjects. Omega-3 FA supplementation reduced the risk of MACE (RR; 0.95; CI: 0.91–0.99; p for heterogeneity 0.27; I2 = 20%; p = 0.03), cardiovascular death (RR; 0.94; CI: 0.89–0.99; p for heterogeneity 0.21; I2 = 25%; p = 0.02), and MI (RR; 0.86; CI: 0.79–0.93; p for heterogeneity 0.28; I2 = 19%; p < 0.01), but had no significant effect on all-cause death, stroke, and revascularization. In the subgroup analysis, omega-3 FA supplementation decreased the incidence of MACE and cardiovascular death in acute patients with MI, the risk of MI and stroke in patients with CHD, and the risk of MI in patients with high-risk CHD. 0.8–1.2 g omega-3 FA supplementation reduced the risk of MACE, cardiovascular death, and MI. It was revealed that gender and diabetes have no significant association between omega-3 FA supplementation and MACE risk. Conclusions Omega-3 FA supplementation had a positive effect in reducing the incidence of MACE, cardiovascular death, MI. Regardless of the stage of CHD, omega-3 FA supplementation can prevent the occurrence of MI. The 0.8–1.2 g omega-3 FA supplementation alleviated CHD risk more effectively than lower or higher doses. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42021282459. show less