Omega-3s and CVD Prevention: A Promising Future?

JoAnn E. Manson, MD, DrPH


November 06, 2019

This transcript has been edited for clarity.

Hello. I am Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts. I'd like to talk with you about a recent updated meta-analysis of randomized trials of omega-3 fatty acids and cardiovascular disease (CVD). I was a coauthor of this meta-analysis.

Our goals were twofold:

  1. To update a meta-analysis including the recent large-scale randomized trials of omega-3s, such as ASCEND, VITAL, and REDUCE-IT; and

  2. To do the meta-analysis with and without the inclusion of data from the REDUCE-IT trial, which was an outlier. This trial used a very high dose (4 g/day) of purified eicosapentaenoic acid (EPA) and found a very large magnitude of risk reduction.

We also wanted to do, for the first time, a dose-response analysis of omega-3s and CVD to see whether there was a dose-response gradient, and to, again, conduct this analysis both with and without REDUCE-IT.

We included 13 randomized trials with more than 127,000 participants in this report. Even in the analyses excluding REDUCE-IT, we saw a significant reduction in myocardial infarction and coronary heart disease death, CVD death, and total CVD events, but no significant reduction in stroke. Only REDUCE-IT showed clear evidence for a significant reduction in stroke, and all of these risk reductions strengthened in the analyses including REDUCE-IT.

In terms of the dose-response analyses, even without including REDUCE-IT, we saw evidence for a dose response, and with the inclusion of REDUCE-IT, the dose-response was approximately 8%-9% reduction in total CVD events per each 1-g increase in the dose of omega-3s (combination docosahexaenoic acid and EPA) or EPA alone.

The more moderate reductions that we saw, on an order of 8%-9% with the lower moderate doses of omega-3s, actually would translate into hundreds of thousands of CVD events averted in the United States, and many more worldwide, given the very high rates of these events. The much larger magnitude of risk reduction seen with REDUCE-IT obviously would translate into more events averted and would be expected to go beyond what would be projected with triglyceride-lowering effects alone.

We need much more research on the effects of high-dose omega-3s, both in secondary and high-risk primary prevention. The VITAL trial is the only study to use a usual-risk population. In a secondary analysis from VITAL, we saw a greater reduction in myocardial infarction among those who had low fish consumption at baseline and in African Americans, but few of these trials have included black persons and few have data on diet at baseline.

Particularly for high-risk primary prevention, it will be important to understand whether omega-3s will begin to fill the void left by decreasing the use of aspirin in the primary prevention population, where aspirin is losing its luster. More research will be tremendously helpful to understand the patient populations most likely to benefit from omega-3s.

Thank you so much for your attention. This is JoAnn Manson

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