GISSI-3 Trial - ACEI and ACEI + Nitrates after Acute MI

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 pathc 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

SAVE Trial - Captopril in HF after MI

What is SAVE Trial?

 Survival And Ventricular Enlargement Study Group.

Tell me about the trial in a brief paragraph? - Quick and Dirty.

Trial looked at capacity of Captopril to reduce the morbidity and mortality in patients with left ventricular failure after a heart attack.


So in short CAPTOPRIL (any ACE Inhibitor) reduces both morbidity and mortality for post-MI patients with asymptomatic heart failure per this trial.


Details of the Trial


Specialty: Cardiology (Heart Failure and MI)


Problem Addressed: Heart Failure (EF<40%) after Myocardial Infarction.


Design:
Randomized placebo controlled trial.


Patients:
Total - 2231 randomly selected 3 to 16 days after a MI. All with EF < 40% and no symptoms of heart failure - so Class 1 to 2.
1115 recieved Captopril
1116  rcieved placebo.

Inclusion Criteria:
Both sexes, 1987 to 1990 (January 27th to 28th). 
 (by MUGA)b/n 21 and 80 years of age


Exclusion Criteria:
Failure to randomize with in 16 days of MI
Serum Cr > 2.5
Contraindication or allergy to ACEI
Another reason to use the ACEI like HTN or CHF symptoms.
Unwillingness to participate.
Unstable course after MI
 Recurrent ischemia with in 72 hour after MI or if they needed further ischemic w/u or treatment.


Average Follow-up: 42 months. Two weeks after randomization, then every three months for first year then every 4 months for second year. 


REPEAT MUGA SCAN TO ASSES LV EJECTION FRACTION AT AN AVERAGE OF 36 MONTHS OF TIME.


Dosage:

Starting 6.25 to 12.5 tid and gradually increased to 25 tid at the time of discharge with a target dose of 50 tid. No BP guidelines were used for titration. Compliance was determined by pill count at follow up.


End Points:

Primary -  All cause mortality - reduced by 5 percent (20 versus 25% in placebo.


Secondary -  Risk Reductions:

Death from Cardiovascular Causes - 21% risk reduction.

CHF requiring hospitalization - 22% risk reduction
CHF requiring ACEI - 37% reduction
Recurrent MI - 25% reduction in risk
Death from CV causes or MI - 22% risk reduction
Death from Cv causes, CHf or MI - 24% risk reduction.

Conclusions:

In patient who had a recent MI addition of ACEI (Captopril) reduces all cause mortality and morbidity even on top of standard beta blockers, aspirin and nitrates.

Importance: 

First trial to show mortality and morbidity reduction by ACEI in post-MI patient with LVEF of < 40% without HF symptoms.

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:

PUBMED LINK HERE

NEJM LINK HERE