[Lisinopril: myocardial infarction, the first 24 hours, in patients with stable hemodynamic status. The GISSI-3 study; results at 6 weeks]

Abstract

The GISSI-3 study is a multicentre randomised trial, the aim of which is to assess the efficacy of lisinopril, of transdermic glyceryl trinitrate and their association on survival and left ventricular function after acute myocardial infarction. Between June 1991 and July 1993, 19,394 patients were randomised in 200 Italian coronary care units. The patients were eligible if admitted within 24 hours of the onset of symptoms, if they had a stable haemodynamic status and in the absence of contraindications to the study drugs. Using a factorial protocol, these patients were randomised to receive either oral lisinopril (5 mg/day as a starting dose followed by 5 mg at the 24th hour and then 10 mg/day) glyceryl trinitrate alone (intravenously for 24 hours followed by 10 mg by transdermic patch) or the association of the two drugs or neither (control group). The principal criteria were global mortality and a parameter of combined events. The combined parameter was defined as the number of deaths plus the number of late (after the 4th day of hospital admission) cases of clinical cardiac failure or of severe left ventricular dysfunction without clinical signs of cardiac failure. Complete clinical information and a six-week follow-up were obtained in 18,895 (97.4%) of randomised patients. The global mortality at 6 weeks was 6.7%. The results of GISSI-3 show that treatment with lisinopril started (in addition to conventional therapy) in clinically stable patients during the first 24 hours of myocardial infarction and continued for 6 weeks significantly reduces (p = 0.03) global mortality at 6 weeks (6.3% in the lisinopril group versus 7.1% in the group without lisinopril), which results in 8 lives saved for every 1,000 patients treated. This "gain in lives" is observed from the first day of treatment. At 6 weeks, the combined morbidity-mortality was 15.6% in the lisinopril group, compared with 17% in the group without lisinopril, a significant reduction of 8%. In patients receiving glyceryl trinitrate, the 6 week mortality was 6.5% (617/9,453) compared with 6.9% (653/9,442) in the group not receiving this treatment; this difference was not significant. There was no significant difference in combined morbidity-mortality between these two groups (15.9 vs 16.7% respectively). The beneficial effect of lisinopril alone or associated with glyceryl trinitrate was also demonstrated on the combined parameter in high risk subgroups (elderly patients and women).(ABSTRACT TRUNCATED AT 400 WORDS)