Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis

Abstract

Purpose of Review Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. Recent Findings Fourteen studies were identified providing data on 125,763 patients. A prespecified cutoff value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). Summary HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.

Dietary fatty acids and CHD: from specific recommendations to dietary patterns

“…Most large RCT v. placebo also support a CHD protective effect in secondary prevention with about a 20 % decrease in CHD death and 30 % decrease in CHD events with doses of EPA þ DHA ≥ 900 mg/d in secondary CHD prevention. This is confirmed by several recent meta-analyses (118,(120)(121)(122)(123)(124)(125)(126) . Negative studies for some of them can be criticised for their lack of power and/or by the use of OO as a placebo.…”

“…They decreased CHD by 10 % (RR 0•90; 95 % CI 0•84, 0•96) and MI by 12 % (RR 0•88; 95 % CI 0•83, 0•94). Lombardi et al (123) (124) , in 2020, included sixteen RCT (81 073 patients with previous CV events, dose of LC n-3 PUFA ≥ 1 g/d for ≥ 1 year). LC n-3 PUFA supplementation was associated with a 9 % decrease in cardiac mortality (RR 0•91; 95 % CI 0•85, 0•98), a 9 % decrease in MACE (RR 0•90; 95 % CI 0•82, 0•99) and a 17 % decrease in MI (RR 0•83; 95 % CI 0•71, 0•98).…”

Secular Decreasing Trend in Plasma Eicosapentaenoic and Docosahexaenoic Acids among Patients with Acute Coronary Syndrome from 2011 to 2019: A Single Center Descriptive Study

“…Although a few clinical studies have shown the effectiveness of n-3 PUFAs in high-risk patients, the benefit of n-3 PUFAs in the prevention of ASCVD remains controversial [31][32][33][34][35][36][37][38][39][40][41][42]. For primary prevention, a study of cardiovascular events in diabetes (ASCEND) [43] and a long-term outcomes study to assess STatin Residual Risk Reduction With EpaNova in HiGh Cardiovascular Risk PatienTs With Hypertriglyceridemia (STRENGTH) [44] failed to show a significant reduction in ASCVD by n-3 PUFA formulation in high risk patients.…”

Dietary Supplements—For Whom? The Current State of Knowledge about the Health Effects of Selected Supplement Use

“…The second 2019 meta-analysis of the studies, from which the REDUCE-IT study was excluded because of the comparatively high level of its omega-3 dose, showed that omega-3 supplementation was associated with lower risk of myocardial infarction by 8%, total coronary heart disease by 5%, coronary heart disease death by 8%, and cardiovascular death by 7% [37]. Further evidence of the beneficial effect of omega-3 fatty acids in reducing cardiovascular risk is also found in the results of two meta-analyses from 2020 [38,39], although there was also an associated higher risk of bleeding events and atrial fibrillation events in some instances [39].…”