Omega-3 Protective Effects Against Sudden Death Start Early – Study

Total mortality among myocardial infarction survivors was significantly lowered after only three months of omega-3 fatty acid supplementation, Italian researchers report in an upcoming issue of Circulation.

The 41% relative risk reduction in total mortality early in treatment was largely due to the decrease in the risk of sudden cardiac death, which "was nearly significant at only three months, accounting for up to 67% of the overall mortality benefit," investigators of the GISSI-Prevenzione trial report.

"It became significant at four months and was highly statistically significant at 42 months, when it accounts for 59% of the n-3 [polyunsaturated fatty acids] advantage on mortality," the investigators say.

Based upon these findings, the researchers conclude: "To save one patient, in a population at relatively low risk (annual mortality 2.8%), 172 patients would need to be treated for one year with n-3 PUFAs."

The Italian researchers say their findings provide "important support to the hypothesis of an antiarrhythmic and/or antifibrillatory role of n-3 PUFAs, which should be formally tested with adequately sized trials on well-defined candidate clinical conditions."

The analysis expands upon earlier findings from the GISSI trial, in which 11,323 patients who had suffered an MI within the previous three months were randomized to omega-3 fatty acids (1 g/day), vitamin E (300 mg/day), both or placebo.

The trial's combined efficacy endpoints were: cumulative rate of all-cause death, nonfatal MI and nonfatal stroke; and the cumulative rate of cardiovascular death, nonfatal MI and nonfatal stroke. Sudden death was not a primary outcome measure, "although its documentation was explicitly foreseen in the collection of end-point events," the researchers note.

In a 1999 Lancet article, the GISSI team reported fatty acid supplementation significantly reduced the risk of death, nonfatal MI and stroke among study participants, including reductions in CV and sudden deaths (¹ (Also see "Fish Oil Supplements Lower Cardiovascular Events, Stroke Risk - Study" - Pink Sheet, 16 Aug, 1999.), p. 14).

In the current study, which was released April 8, the GISSI investigators conducted a detailed analysis of the time course of the fatty acids benefit, "focusing on the different causes of death in the early phase of treatment, to explore the hypothesis of an antiar-rhythmic effect of the drug on sudden death."

The investigators also found significant reductions in cardiac death at six months, and in coronary and CV deaths at eight months in the supplement group.

In a separate study, Boston researchers found blood levels of the fatty acids are "strongly associated" with a reduced sudden death risk among men without evidence of prior CV disease.

Christine Albert, MD, Brigham & Women's Hospital, et al., conducted a prospective, nested case-control analysis among healthy men followed for up to 17 years in the Physicians' Health Study. Researchers analyzed fatty acid composition of previously collected blood for 94 participants whose first manifestation of CV disease was sudden death. The subjects were matched with 184 controls.

Published in the April 11 New England Journal of Medicine, the study reports a statistically significant, linear inverse association between baseline blood fatty acid levels and sudden death risk. "As compared with men with levels of long-chain n-3 fatty acids in the lowest quartile, those with levels in the highest quartile had an 81% lower risk of sudden death," Albert and colleagues say.

They note that more than 50% of all sudden cardiac deaths occur in individuals with no history of the disease. "If the observed association is causal, increasing the intake of n-3 fatty acids by eating more fish or by taking supplements is an intervention that could be applied to this segment of the population at low cost and little risk," Albert et al. suggest.

In a third study on fatty acids released the same week, Harvard School of Public Health researchers found higher consumption of fish and omega-3s to be inversely associated with reduced risk of coronary heart disease, and CHD deaths in particular, in women.

In the April 10 Journal of the American Medical Association, Frank Hu, MD, et al. report on their analysis of dietary consumption and follow-up data from 84,688 women in the Nurses' Health Study.

"Intake of omega-3 fatty acids was significantly associated with a lower risk of CHD death among regular aspirin users and nonusers. In contrast, the inverse association between omega-3 fatty acids and nonfatal MI was significant only among women who did not use aspirin regularly," Hu et al. say.