A Bayesian analysis of the VITAL trial: effects of ω-3 fatty acid supplementation on cardiovascular events

Abstract

Background: Effects of ω-3 fatty acids (FAs) supplementation on cardiovascular outcomes have been investigated in several randomized controlled trials (RCTs). The VITamin D and OmegA-3 TriaL (VITAL) is the largest trial that tested the effect of ω-3 FA supplementation (840 mg/d of eicosapentaenoic acid and docosahexaenoic acid in 1.2:1) in a primary prevention population in the United States, with nonsignificant results (P > 0.05) for major cardiovascular disease (CVD) events.

Objectives: To reanalyze VITAL using Bayesian methods accounting for prior evidence.

Methods: The VITAL randomly assigned 25,871 older United States adults with a median follow-up of 5.3 y. On the basis of prior evidence from RCTs, we used Weibull proportional hazards models adopting the Hamiltonian Monte Carlo sampling method to estimate posterior hazard ratio (HR) for total CAD, myocardial infarction (MI), composite major CVD events (CAD/stroke/CVD death), CVD death, all-cause death, and stroke. Several distinct informative priors were formulated based on Bayesian hierarchical models of previous trials similar to VITAL.

Results: Bayesian analyses with the use of noninformative prior yielded essentially the same results as the corresponding frequentist analyses. The effects of ω-3 FA supplementation on CAD and MI were robust across the priors, with the posterior HR estimates varying from 0.88 to 0.93 and 0.82 to 0.90, respectively. Without skepticism into the priors, posterior HRs were 0.95-0.96 in CVD, 0.91-0.92 in cardiovascular death, and 0.95-0.96 in all-cause death risks, respectively. Stroke risk was unchanged by the intervention. According to primary informed priors, probabilities of ω-3 FA being effective were 99.7% for CAD, 99.6% for total MI, 98.4% for CVD, 98.8% for all-cause death, 99.8% for cardiovascular death, and 33.7% for stroke, respectively.

Conclusions: Bayesian analyses of VITAL incorporating previous RCT evidence suggest that daily ω-3 FA supplementation robustly lowers risk of coronary events but not stroke, providing enhanced support for the primary prevention use of ω-3 FA supplementation for coronary events.

Trial registration number: This study was registered at VITAL clinicaltrials.gov identifier as NCT01169259.

Keywords: Bayesian analysis; cardiovascular disease; coronary artery disease; randomized controlled trial; ω-3 fatty acids.