Clinical studies: GISSI-3
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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.

Results:

  • 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).

References:

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; 343: 1115-1122.
Gruppo 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.


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GISSI Coordinating Centre
"Mario Negri" Institute for Pharmacological Research

Via Eritrea, 62 - 20157 Milano - Italy
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Scientific Info:DepCardio
Technical Info:Enrico Nicolis