P5328Meta-analysis for omega-3 supplementation and cardiovascular disease

Abstract

Background/Introduction: Omega-3 polyunsaturated fatty acid (PUFA) supplements are being extensively used for the prevention of cardiovascular (CV) disease. Purpose(s): To evaluate the effect of omega-3 supplementation on major CV outcomes. Method(s):We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2017. We included all randomized clinical trials assessing omega-3 supplementation on all-cause mortality, cardiac death, sudden death, myocardial infarction (MI), and stroke. We used 2 complementary approaches: classic meta-analysis and Trial Sequential Analysis (TSA). TSA is a cumulative meta-analysis evaluating whether the required Information Size (IS) needed to answer with certainty the research question has been reached; it also adjusts the statistical significance thresholds called monitoring boundaries to eliminate the type I error from repeated testing. The principal summary measures were the relative risk (RR) and the absolute risk reduction (RD). Heterogeneity was assessed by Q statistic and its extent by I2. Sensitivity analyses addressed the role of blinding, prevention setting, atrial fibrillation, implantable cardioverter-defibrillator, and hemodialysis. Meta-regression analysis was performed for omega-3 dose. We estimated with TSA the required IS to detect a 10% RR reduction in the intervention arm with 80% power (beta=0.2) and type I error alpha=0.05 (two-sided test). Result(s): Twenty one studies with 80,821 randomized patients were included from 4,339 originally retrieved citations reporting 7,357 deaths, 3,759 cardiac deaths, 1,135 sudden deaths, 1,980 MIs, and 1,705 strokes. Omega-3 supplements were not statistically significantly associated after correction for multiple comparisons (p value threshold for significance <0.0063) with reduced all-cause mortality (RR, 0.97; 95% CI, 0.93 to 1.02; p=0.21; I2=13%; RD, 0.00; 95% CI, -0.01 to 0.00; p=0.21; I2=30%), cardiac death (RR, 0.92; 95% CI, 0.87 to 0.98; p=0.008; I2=6%; RD, -0.01; 95% CI, -0.01 to 0.00; p=0.10; I2=70%), sudden death (RR, 0.90; 95% CI, 0.80 to 1.01; p=0.06; I2=20%; RD, 0.00; 95% CI -0.01 to 0.00; p=0.37; I2=71%), MI (RR, 0.95; 95% CI, 0.87 to 1.03; p=0.21; I2=32%; RD, 0.00; 95% CI, -0.00 to 0.00; p=0.21; I2=27%) or stroke (RR, 1.06; 95% CI, 0.97 to 1.17; p=0.21; I2=19%; RD, 0.00; 95% CI, -0.00 to 0.00; p=0.21; I2=7%). TSA showed that the only meta-analysis which reached the required IS to observe a 10% RR reduction was for all-cause mortality; all other meta-analyses where underpowered. Conclusion(s): Omega-3 supplements do not seem to exert an undisputable benefit on mortality and major CV outcomes.