Supplementation of vitamin D or marine n-3 fatty acids may not lower the incidence of major cardiovascular events or invasive cancer vs. placebo, according to results from the VITAL trial presented Nov. 10 at AHA 2018 in Chicago, IL, and simultaneously published in two papers in the New England Journal of Medicine.

JoAnn E. Manson, MD, PhD, et al., conducted a randomized, placebo-controlled trial with a 2x2 factorial design looking at 25,871 participants with a mean age of 67.1 years. Participants were randomized to a dose of 2,000 IU of vitamin D3 per day, and a dose of 1 g of n-3 fatty acid per day.

Results showed at a median follow-up of 5.3 years the primary endpoint of a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes) occurred in 396 participants in the vitamin D group, and 409 in the placebo group; and 386 participants in the n-3 group and 419 in the placebo group. Further, invasive cancer was diagnosed in 793 participants in the vitamin D group and 824 in the placebo group; and 820 participants in the n-3 group and 797 in the placebo group.

Secondary endpoints in the n-3 vs. placebo group showed that hazard ratios were 0.93 for the expanded composite end point of cardiovascular events; 0.72 for total myocardial infarction; 1.04 for total stroke; 0.96 for death from cardiovascular causes; and 0.97 for death from cancer. Secondary endpoints in the vitamin D vs. placebo group showed that hazard ratios were 0.96 for the expanded composite end point of major cardiovascular events plus coronary revascularization; 0.96 for myocardial infarction; 0.95 for stroke; 1.11 for death from cardiovascular causes.

The authors note that a strength of their trial is a large general population sample with racial, ethnic group and geographic diversity. Further, they conclude that "[their] finding of a possible lower incidence of the primary cardiovascular end point with n-3 supplementation than with placebo among participants with low fish consumption – a characteristic that has rarely been examined as an effect modifier in previous trials – is hypothesis-generating."

They conclude that moving forward, "the results of ongoing trials that are testing higher doses in high-risk populations will be informative but may not apply to primary prevention."

In an editorial comment from John F. Keaney, Jr., MD, FACC, and Clifford J. Rosen, MD, add that "Despite the negative findings regarding the primary end points in VITAL, the secondary end points will undoubtedly draw attention … these 'positive' results need to be interpreted with caution."

Keywords: AHA18, AHA Annual Scientific Sessions, Vitamin D, Vitamins, Fatty Acids, Omega-3, Primary Prevention, Cholestanes, Neoplasms

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