GISSI-3Trial - ACEI and ACEI+Nitrates after Acute Myocardial Infarction

What Does GISSI-3 Stand for? - GOT NOTHING TO DO WITH THE TRIAL RESULTS Its and Italian research consortium which is spelled - (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico)

Quick & Dirty about GISSI-3:

6 weeks of oral Lisinopril an ACEI with or without Nitrates reduces overall mortality and major adverse cardiac events (MACE) after and ACUTE MYOCARDIAL INFARCTION. (AMI/ACS).

Details of the Trial
Specialty: Cardiology (Acute Coronary Syndrome, CHF after MI and MACE)

Problem Addressed: Efficacy of ACEI +/- Transdermal Nitrates after acute MI (<24 hours)

Design: Randomized trial - Patients' were randomized either to lisinopril arm or Nitrate arm or Both or None - a 2x2 randomized design.

Patients:

Total - 19394 patients.
Lisinopril Group - 9435, Control- 9460
Nitrate Group - 9453, Control - 9442.

Inclusion Criteria:Patients were deemed eligible if they were admitted with typical chest pain with ST changes as below

≥1mm ST elevation or depression in ≥1 limb leads
≥2mm ST elevation or depression in ≥1 chest leads
Admitted to CCU within 24h of symptom onset
And no clear indication to sutdy treatment

Exclusion Criteria:

Severe CHF requiring any of study treatment (either Lisinopril or Nitro) Killip class 4 High risk of further serious hemodynamic deterioration after treatment with vasodilators, judged by SBP≤100 mmHg Contraindications to study drugs: -History of renal failure (creatinine ≥2mg/dl, proteinuria >500mg/24h, or both) -History of bilateral renal artery stenosis -Documented allergy to study drug -Other life-threatening disorders

Average Follow-up:

6 weeks after randomization.

Dosage or Intervention:

Lisinopril initially 5 mg and then 10 mg - extrapolated to other ACEI's, with or without Nitrates - initially intravenous and then transdermal 10mg/24 hours.

Treatment Groups - Classic 2x2 design

1. Lisinopril only
2. Placebo only
3. Nitro only
4. Both nitro and Lisinopril

End Points:Primary -

All cause mortality and Combined all cause mortality + CHF or extensive myocardial damager after day 4 of hospitalization. (myocardial damage defined as EF < 35% or damage to > 45%^ of myocardium on echo).

Secondary -

Clinical CHF
LVEF ≤35%
≥45% akinesis/dyskinesis
Reinfarction
Post-infarction angina
CABG
PTCA
SBP <90 mmHg for >1 h
Cardiogenic shock
Renal dysfunction
Stroke

Conclusions: Use of Lisinopril within 24h of Myocardial Infarction Significantly reduced mortality at 6 weeks of therapy by a statistically significant 11%

No survival benefit from Nitrglycerine patch alone (remember it is patch not oral nitrates), but combination of Nitroglycerine and Lisinopril improved end points than just Lisinopril alone.

Benefits present in pre-defined high risk populations of females & those >70 years old

Statistics:

With Lisinopril alone:

• overall mortality at 6 weeks (odds ratio = 0.88)
• severe ventricular dysfunction (odds ratio = 0.90)

Combination of Lisinopril and Nitrates (transdermal):

severe ventricular dysfunction (odds ratio = 0.85)

overall mortality at 6 weeks (odds ratio = 0.83)

Importance:

First trial to show mortality and morbidity reduction by ACEI when used with in 24 hours of acute MI.

For other -ACEI trials please see the links for ACEI trials on the main cardiologytrials page @http://cardiologytrials.blogspot.com

Here are some images and links: 

PUBMEDLINK HERE

LANCET LINK HERE