GISSI-3

Summary:

Evaluated lisinopril versus transdermal glyceryl trinitrate individually and both combined for 6 week mortality after acute myocardial infarction. Lisinopril when given within 24 hours of acute MI reduced mortality by 11% at 6 weeks. No benefit for transdermal glyceryl trinitrate. This led to the use of ACE inhibitors for acute myocardial infarction patients.

Original Publication:

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

Trial Details:

Eponym: Gruppo Italiano per lo Studio della Sopravvivenza nell’infarcto Micardico.

Purpose: To evaluate the use of ACE inhibitors after myocardial infarction on mortality both individually and in combination with transdermal glyceryl trinitrate.

Format: Double blind, multicenter, randomized, placebo controlled

Treatment Group: Either lisinopril or combination of lisinopril and transdermal glyceryl trinitrate

Control Group: Placebo

Number of Patients: 19.394

Inclusion Criteria: Typical anginal chest pains, symptoms < 24 hours and one the following ECG findings

  • Limb leads ≥ 1 mm ST depression or elevation
  • Precordial leads ≥ 2 mm ST depression or elevation

Exclusion Criteria:

  • Severe congestive heart failure
  • Killip Class IV
  • Systolic blood pressure < 100 mmHg
  • Contraindication for the study drugs (i.e. hyperkalemia, renal failure or allergy for lisinopril)

Follow-up: 6 months

Primary Endpoint:

  • All-cause mortality at 6 weeks
  • Composite of death, congestive heart failure, left ventricular ejection fraction < 35% or left ventricular ejection fraction > 45% with an akinetic or dyskinetic segment

Secondary Endpoint:

  • Clinical heart failure
  • Left ventricular ejection fraction < 35%
  • Left ventricular ejection fraction > 45% with dyskinetic or akinetic segment
  • Reinfarction
  • Post-infarct angina
  • Coronary revascularization (CABG or PTCA)
  • Systolic blood pressure < 90 mmHg for > 1 hour
  • Cardiogenic shock
  • Renal dysfunction
  • Stroke