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Italian Study Group - Prevention - GISSI-Prevention
Description:
Pravastatin and antioxidants for secondary prevention of death/MI/stroke.
Hypothesis:
To test the effectiveness of low-dose pravastatin and antioxidants on post myocardial infarction patients
Study Design
Study Design:
Patients Screened: Not given
Patients Enrolled: 4,271
Mean Follow Up: 42 months
Mean Patient Age: 59
Female: 15
Patient Populations:
Subjects presenting within 3 months of an acute myocardial infarction
Informed consent
Exclusions:
Unfavorable prognosis
Clear contraindication to treatment (ie, allergy)
Mental or physical disorders
Primary Endpoints:
Composite death/MI/Stroke
Drug/Procedures Used:
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.
Principal Findings:
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.
Interpretation:
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.
References:
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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