Objective: Evaluation of the efficacy of a treatment with ACE-inhibitors
and/or nitrates on 6-week mortality following acute myocardial infarction
(AMI); evaluation of the extent to which such a favourable effect on left
ventricular function (measured at 6 weeks), if present, is maintained up
to 6 months following the event. The evaluation is carried out on the combined
endpoint of mortality and left ventricular damage.
Study design: Open controlled clinical trial with central randomisation
of patients following a 2x2 factorial design to treatment with lisinopril,
nitrate, both or neither within 24 hours of initial symptoms. Treatments
are administered for 6 weeks.
Population randomised: 19.394 patients in 24 months, from June 1991
or July 1993. The study was preceded by a pilot phase on 1526 patients.
lisinopril treatment determined a significant reduction in the combined endpoint
of mortality and signs/symptom of left ventricular failure at six weeks:
lisinopril 15.6% vs no lisinopril 17% (2p= 0.009, OR 0.90, 95%CI 0.84-0.98);
lisinopril treatment determined a significant reduction also of mortality
alone at six weeks: lisinopril 6.3% vs no lisinopril 7.1%, 11% relative reduction
(2p=0.03, OR 0.88, 95%CI: 0.79-0.99)
six-week mortality was 6.5% among patients treated with nitrates and 6.9%
among patients not receiving nitrates (non significant difference, 2p=0.28,
OR 0.94, 95%CI: 0.84-1.05); no significant difference emerged between the
two groups also with respect to the combined endpoint: nitrates 15.9% vs
no nitrates 16.7% (2p=0.12, OR 0.94, 95%CI: 0.87-1.02);
six months after the AMI, the combined endpoint is still significantly reduced
among patients treated with lisinopril (lisinopril 18.1% vs no lisinopril
19.3%, 2p=0.03, OR 0.92, 95%CI: 0.86-0.99), while among those treated with
nitrates it appears substantially equivalent to that of controls (nitrates
18.4% vs no nitraties18.9%, 2p=0.39, OR 0.97, 95%CI: 0.90-1.04).
Associazione Nazionale Medici
Cardiologi Ospedalieri-ANMCO , Istituto di Ricerche Farmacologiche "Mario
Negri" . Protocollo di ricerca GISSI-3. G Ital Cardiol 1991; 21: 779-788.
GISSI-3 Gruppo Italiano per lo
Studio della Sopravvivenza dell'Infarto Miocardico . GISSI-3: Study protocol
on the effects of lisinopril, of nitrates, and of their association in patients
with acute myocardial infarction. Am J Cardiol 1992; 70: 62C-69C.
Gruppo Italiano per lo Studio
della Sopravvivenza dell'Infarto Miocardico . GISSI-3: effects of lisinopril
and transderman glyceryl trinitrate singly and together on 6-week mortality
and ventricular function after acute myocardial infarction. Lancet 1994;
Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico . Six-month
effects of early treatment with lisinopril and transdermal glyceryl trinitrate
singly and together withdrawn six weeks after acute myocardial infarction:
The GISSI-3 trial. J Am Coll Cardiol 1996; 27: 337-344.