A total of 11,323 patients were recruited and randomised at 172 centres, making GISSIPrevenzione one of the largest studies in secondary prevention. Information on end-of-study vital status was recorded for 99.9% of participants, yielding more than 38,000 patient years of data during an average 3.5 years of follow-up.
GISSI-Prevenzione had two pre-specified primary efficacy end-points.
1. Cumulative rate of all-cause mortality, non-fatal MI and non-fatal stroke.
2. Cumulative rate of cardiovascular mortality, nonfatal MI and non-fatal stroke.
Highly purified omega-3 PUFAs significantly reduced the risk of experiencing a primary end-point event in GISSI-Prevenzione. Compared with controls, the risk reduction for the end-point of allcause mortality plus non-fatal MI and non-fatal stroke was 15% to 16% (P = 0.02); the risk reduction for cardiovascular death plus non-fatal MI and nonfatal stroke was 20% to 21% (P = 0.006).7,8,10 The reduction in risk of a primary end-point event with omega-3 PUFAs during the GISSI-Prevenzione study emerged within a few months and was then sustained throughout follow-up (see Figure 1).
Analysis of cause-specific mortality revealed that prevention of primary end-point events by highly purified omega-3 PUFAs was due to reduction in allcause mortality (21% risk reduction; P = 0.01) and in several categories of cardiovascular death, notably sudden death (44% risk reduction; P = 0.0006).7,8,10 There was no significant impact on patients™ risk of experiencing a non-fatal MI or non-fatal stroke.
The findings of the secondary end-point analysis and the observation that risk of a primary end-point event was reduced within a few months of starting highly purified omega-3 PUFA therapy stimulated a further analysis of factors contributing to this result.8 This analysis confirmed an early treatment benefit on total survival that was significantly better than in the control group after three months (41% risk reduction; P = 0.037) and thereafter remained statistically significant and clinically meaningful for the remainder of the study.8 A similar censored analysis of these events revealed an early effect of highly purified omega-3 PUFAs in reducing risk of sudden death, with a large (53%) and statistically significant (P = 0.048) benefit apparent after four months.8 The reduction in sudden death at three months, although not statistically significant (P = 0.058) accounted for more than half of the reduction in total mortality at that time. By the end of followup the reduction in sudden death was highly statistically significant (P = 0.0006) and accounted for 59% of the total survival benefit of highly purified omega-3 PUFAs versus controls.
- E Braunwald, ├óÔé¼┼øEvolution of the Management of Acute Myocardial Infarction: A 20th Century Saga├óÔé¼┼Ñ, Lancet, 352 (1998), pp. 1,771├óÔé¼ÔÇ£1,774.
- S Capewell, B M Livingston, K MacIntyre K, et al., ├óÔé¼┼øTrends in Case-fatality in 117,718 Patients Admitted with Acute Myocardial Infarction in Scotland├óÔé¼┼Ñ, Eur. Heart J., 21 (2000), pp. 1,833├óÔé¼ÔÇ£1,840.
- S M Haffner, S Lehto, T R─é┬Ânnemaa, et al., ├óÔé¼┼øMortality from Coronary Heart Disease in Subjects with Type-2 Diabetes and in Non-diabetic Subjects With and Without Prior Myocardial Infarction├óÔé¼┼Ñ, N. Engl. J. Med., 339 (1998), pp. 229├óÔé¼ÔÇ£234.
- F C Lampe, P H Whincup, S G Wannamethee, et al., ├óÔé¼┼øThe Natural History of Prevalent Ischaemic Heart Disease in Middle-aged Men├óÔé¼┼Ñ, Eur. Heart J., 21 (2000), pp. 1,052├óÔé¼ÔÇ£1,062.
- M de Lorgeril and P Salen, ├óÔé¼┼øDiet as Preventive Medicine in Cardiology├óÔé¼┼Ñ, Curr. Opin. Cardiol., 15 (2000), pp. 364├óÔé¼ÔÇ£370.
- S G Priori, E Aliot, C Blomstrom-Lundqvist, et al., ├óÔé¼┼øTask Force on Sudden Cardiac Death of the European Society of Cardiology├óÔé¼┼Ñ, Eur. Heart J., 22 (2001), pp. 1,374├óÔé¼ÔÇ£1,450.
- GISSI-Prevenzione Investigators, ├óÔé¼┼øDietary Supplementation with N-3 Polyunsaturated Fatty Acids and Vitamin E After Myocardial Infarction: Results of the GISSI-Prevenzione Trial├óÔé¼┼Ñ, Lancet, 354 (1999), pp. 447├óÔé¼ÔÇ£455.
- R Marchioli, F Barzi, E Bomba, et al., ├óÔé¼┼øEarly Protection Against Sudden Death by N-3 Polyunsaturated Fatty Acids After Myocardial Infarction: Time-course Analysis of the Results of Gruppo Italiano per lo Studio Della Sopravvivenza nell™Infarto Miocardico (GISSI)-Prevenzione├óÔé¼┼Ñ, Circulation, 105 (2002), pp. 1,897├óÔé¼ÔÇ£1,903.
- Omacor SmPC, Solvay Pharmaceuticals GmBH.
- R Marchioli, on behalf of the GISSI-Prevenzione Investigators, ├óÔé¼┼øTreatment with N-3 Polyunsaturated Fatty Acids After Myocardial Infarction: Results of GISSI-Prevenzione Trial├óÔé¼┼Ñ, Eur. Heart J. Suppl., 3 (2001) (Suppl. D), pp. D85├óÔé¼ÔÇ£D97.
- D Wood, de Backer, O Faergemann, et al., ├óÔé¼┼øPrevention of Coronary Heart Disease in Clinical Practice: Recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention├óÔé¼┼Ñ, Eur. Heart J., 19 (1998), pp. 1,434├óÔé¼ÔÇ£1,503.
- M L Burr, ├óÔé¼┼øReflections on the Diet and Reinfarction Trial (DART)├óÔé¼┼Ñ, Eur. Heart J. Suppl., 3 (2001) (Suppl. D), pp. D75├óÔé¼ÔÇ£D78. 13. S C Smith,
- S N Blair, M H Criqui, et al., ├óÔé¼┼øPreventing Heart Attack and Death in Patients with Coronary Disease├óÔé¼┼Ñ, J. Am. Coll. Cardiol., 26 (1995), pp. 292├óÔé¼ÔÇ£294.
- S C Smith, S N Blair, R O Bonow, et al., ├óÔé¼┼øAHA/ACC Guidelines for Preventing Heart Attack and Death in Patients with Atherosclerotic Cardiovascular Disease: 2001 Update. A Statement for Healthcare Professionals from the American Heart Association and the American College of Cardiology├óÔé¼┼Ñ, Circulation, 104 (2001), pp. 1,577├óÔé¼ÔÇ£1,579.
- M G Franzosi, M Brunetti, R Marchioli, et al., ├óÔé¼┼øCost-effectiveness Analysis of N-3 Polyunsaturated Fatty Acids (PUFA) After Myocardial Infarction├óÔé¼┼Ñ, Pharmacoeconomics, 19 (2001), pp. 411├óÔé¼ÔÇ£420.
- T O Tengs , M E Adams, J S Pliskin, et al., ├óÔé¼┼øFive-hundred Life-saving Interventions and Their Cost-effectiveness├óÔé¼┼Ñ, Risk Analysis, 15 (1995), pp. 369├óÔé¼ÔÇ£390.
- G Boriani, M Biffi, C Martignani, et al., ├óÔé¼┼øCost-effectiveness of Implantable Cardioverter-defibrillators├óÔé¼┼Ñ, Eur. Heart J., 22 (2001), pp. 990├óÔé¼ÔÇ£996.