GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico

Lancet. 1994 May 7;343(8906):1115-22.


GISSI-3 is a multicentre randomised clinical trial to assess the efficacy of lisinopril, transdermal glyceryl trinitrate (GTN), and their combination in improving survival and ventricular function after acute myocardial infarction (AMI). Between June, 1991, and July, 1993, 19,394 patients were randomised from 200 coronary care units in Italy. Eligible patients presented within 24 h of symptom onset and had no clear indications for or against the study treatments. In a factorial design patients were randomly assigned 6 weeks of oral lisinopril (5 mg initial dose and then 10 mg daily) or open control as well as nitrates (intravenous for the first 24 h followed by transdermal GTN 10 mg daily) or open control. Complete clinical data and 6-week follow-up were available for 18,895 (97.4%) patients randomised. Two-dimensional echocardiographic data were available for 14,209 patients. Overall 6-week mortality was 6.7%. Lisinopril, started within 24 h from AMI symptoms, produced significant reductions in overall mortality (odds ratio 0.88 [95% CI 0.79-0.99]) and in the combined outcome measure of mortality and severe ventricular dysfunction (0.90 [0.84-0.98]). In the same trial the systematic administration of transdermal GTN did not show any independent effect on the same outcome measures (0.94 [0.84-1.05] and 0.94 [0.87-1.02]). Systematic combined administration of lisinopril and GTN also produced significant reductions in overall mortality (0.83 [0.70-0.97]) and in the combined endpoint (0.85 [0.76-0.94]). The favourable effect of lisinopril alone or with GTN was clear also in the predefined high-risk populations (elderly patients and women) for the combined endpoint. These findings were obtained in a population intensively exposed to recommended treatments (thrombolysis 72%, beta-blockade 31%, and aspirin 84%); non-protocol treatment with angiotensin-converting-enzyme inhibitors and nitrates was allowed for specific clinical indications. No excess of unfavourable clinically relevant events in the treated groups was reported.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Aged
  • Clinical Protocols
  • Creatinine / blood
  • Drug Therapy, Combination
  • Echocardiography
  • Electrocardiography
  • Female
  • Humans
  • Infusions, Intravenous
  • Lisinopril / administration & dosage
  • Lisinopril / therapeutic use*
  • Male
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Nitroglycerin / administration & dosage
  • Nitroglycerin / therapeutic use*
  • Odds Ratio
  • Risk Factors
  • Survival Rate


  • Creatinine
  • Lisinopril
  • Nitroglycerin