The reanalysis1 of the results of the GISSI-Prevenzione secondary prevention trial appearing in this issue of Circulation greatly increases the importance of this large, well-conducted clinical trial. The original publication of the GISSI-Prevenzione reported that when 11,323 patients surviving a very recent myocardial infarction (MI) were randomized to 1.0 g daily of a concentrate of fish oil n-3 polyunsaturated fatty acids (PUFAs, n=2835), vitamin E (300 mg daily, n=2830), both (n=2830), or no treatment (n=2828) on top of usual pharmacological treatment and lifestyle, significant reductions in mortality were observed over the 42 months of follow-up.

However, probably two or three features of the outcome drew the attention of the investigators. These were
(1) the very early separation of the mortality curves (or probability of mortality) between the subjects receiving the n-3 supplement versus the control groups,
(2) the absence of any reduction in plasma cholesterol levels, and
(3) the finding that the major factor in the mortality reduction by n-3 PUFAs resulted from a striking 45% reduction in sudden cardiac deaths, which had not been a stated primary end point for the GISSI-Prevenzione trial.

Indeed, an early reduction in mortality has become a hallmark of the beneficial effects of n-3 PUFAs on coronary heart disease. This relationship is further strengthened when the benefit occurs in the absence of a reduction in cholesterol levels. Both were noted by Burr and associates in their 1989 publication of the Death and Reinfarction Trial and in the Lyon Heart Study by DeLorgeril et al in 1994.

So the GISSI Investigators wisely decided that a careful time-course analysis of the results of GISSI-Prevenzione was warranted, and their resulting present publication adds greatly to the importance of their investigations.

PMID: 11997268

See following website for full manuscript.