Italian Study Group - Prevention - GISSI-Prevention
Pravastatin and antioxidants for secondary prevention of death/MI/stroke.
To test the effectiveness of low-dose pravastatin and antioxidants on post myocardial infarction patients
Patients Screened: Not given
Patients Enrolled: 4,271
Mean Follow Up: 42 months
Mean Patient Age: 59
Subjects presenting within 3 months of an acute myocardial infarction
Clear contraindication to treatment (ie, allergy)
Mental or physical disorders
Fish oil (n3 PUFA) (1 gm./day); Vitamin E (300 mg./day); both, or neither; second randomization after 3-6 months to pravistatin vs. control if total cholesterol > 200 mg/dl.
The GISSI - Prevention trial was stopped prematurely after the results of other studies (4S, WOSCOPS) were published. As a result of these other studies, 19.4% of the patients in the control group started a cholesterol lowering treatment during the follow-up period.
The intention-to-treat analysis showed a 10% reduction in total cholesterol and a 15% reduction in LDL cholesterol, and the by-treatment data showed a 13% reduction in total cholesterol and a 19% reduction in LDL cholesterol.
In the pravastatin group, 14.8% of the patients permanently discontinued therapy (3.1% because of side effects and the others because of patients' reluctance to continue).
There was a 10% risk reduction in patients receiving n-3 PUFA compared with the control group (combined endpoint 13.7% vs. 12.4%), which was statistically significant (log rank P-value 0.045). However, the risk reduction in patients receiving vitamin E was only 4.7% compared with controls, which was not statistically significant. When the combined endpoint variables were analyzed separately, the only statistically significant variable was death. Patients receiving n-3 PUFA had a 45% reduced risk of death compared with control. The patients in the vitamin E group and in the combined group had a reduced risk of death of 35% and 25%, respectively. Patients appeared to tolerate both drugs equally well. The most commonly cited adverse effect was GI intolerance.
The premature stopping of the trial hampered its statistical power. The investigators also concluded that low-dose pravastatin is probably effective in reducing post MI events. The investigators conclude that n-3 PUFA, but not vitamin E nor the combination of the two, significantly increased the combined endpoint of death, nonfatal myocardial infarction, and stroke during the 3.5-year follow-up period. The primary benefit seen in the n-3 PUFA treatment was a lower risk of death. No additive benefits were seen when n-3 PUFA was combined with vitamin E. Put another way, up to 20 lives could be saved per 1000 postinfarct persons treated with n-3 PUFA. Vitamin E has no significant impact on the given combined endpoint.
1. Presented at the XXth Congress of the European Society of Cardiology, Vienna, 1998
2. Presented at the ACC 48th Scientific Sessions, New Orleans, LA, 1999
Keywords: Stroke, Myocardial Infarction, Cholesterol, LDL, Fish Oils, Risk Reduction Behavior, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Secondary Prevention, alpha-Tocopherol, Fatty Acids, Omega-3, Pravastatin, Intention to Treat Analysis, Informed Consent
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