Effects of omega-3 fatty acids on coronary revascularization and cardiovascular events: a meta-analysis

Aims Benefits of pharmacologic omega-3 fatty acid administration in cardiovascular prevention are controversial. Particularly, effects on coronary revascularization are unclear; also debated are specific benefits of eicosapentaenoic acid (EPA). We investigated incident coronary revascularizations, myocardial infarction (MI), stroke, heart failure (HF), unstable angina, and cardiovascular death, in subjects randomized to receive EPA or EPA + docosahexaenoic acid (EPA + DHA) vs. control.Methods and results Meta-analysis of randomized controlled trials (RCTs) was conducted after MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library search. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were pooled using a random effects model. Eighteen RCTs with 134 144 participants (primary and secondary cardiovascular prevention) receiving DHA + EPA (n = 52 498), EPA alone (n = 14 640), or control/placebo (n = 67 006) were included. Follow-up ranged from 4.5 months to 7.4 years. Overall, compared with controls, omega-3 supplementation reduced the risk of revascularization [0.90, 95% confidence interval (CI) 0.84-0.98; P = 0.001; P-heterogeneity = 0.0002; I2 = 68%], MI (0.89, 95% CI 0.81-0.98; P = 0.02; P-heterogeneity = 0.06; I2 = 41%), and cardiovascular death (0.92, 95% CI 0.85-0.99; P = 0.02; P-heterogeneity = 0.13; I2 = 33%). Lower risk was still observed in trials where most participants (>= 60%) were on statin therapy. Compared with DHA + EPA, EPA alone showed a further significant risk reduction of revascularizations (0.76, 95% CI 0.65-0.88; P = 0.0002; P-interaction = 0.005) and all outcomes except HF.Conclusion Omega-3 fatty acid supplementation reduced the risk of cardiovascular events and coronary revascularization, regardless of background statin use. Eicosapentaenoic acid alone produced greater benefits. The role of specific omega-3 molecules in primary vs. secondary prevention and the potential benefits of reduced revascularizations on overall health status and cost savings warrant further research. It is debated whether pharmacologic administration of omega-3 fatty acids reduces cardiac events. In particular, it is unclear whether benefits are actually restricted to the use of eicosapentaenoic acid (EPA), or whether combined administration of EPA + docosahexaenoic acid (DHA) is needed; furthermore, little is known about possible benefits of omega-3 fatty acids in reducing incidence of coronary revascularization procedures. In this meta-analysis of all published evidence of clinical trials comparing EPA alone or EPA + DHA vs. control (134 144 participants), we demonstrate the following: In the overall analysis of all trials, omega-3 supplementation reduced the risk of myocardial infarction and cardiovascular death, to a modest extent. However, when trials administering EPA alone were separately analysed, a further significant risk reduction for cardiovascular outcomes was demonstrated. Importantly, these benefits were also observed in subjects who were already taking statins as part of their chronic therapy.Administration of omega-3 fatty acids, particularly EPA alone, was also associated with a substantial decrease in the risk for subsequent coronary revascularizations. Reduction of revascularization procedures may induce additional benefits on overall health status and associated cost savings.