This document summarizes a clinical trial that evaluated the effect of the selective aldosterone blocker eplerenone in patients with left ventricular dysfunction after myocardial infarction. The trial involved over 6,600 patients who received either eplerenone or a placebo in addition to optimal medical therapy. The results showed that eplerenone reduced all-cause mortality by 14.4% compared to 16.7% for placebo and reduced cardiovascular mortality and hospitalization. However, there was an increased risk of serious hyperkalemia with eplerenone. The study concluded that eplerenone improves outcomes for patients with left ventricular dysfunction after a myocardial infarction when added to maximal medical therapy.

1. Eplerenone, a Selective
Aldosterone Blocker, in Patients
with Left Ventricular Dysfunction
after Myocardial Infarction
(EPHEUSIS Trial)
By
Dr Salman Ahmed

2. Introduction
 Aim to evaluate the effect of epleronone
in pts with acute MI complicated by LVD.
 It is a selective potassium channel
inhibitor thought to improve ventricular
remodelling,redues coronary vascular
inflamation and attenuate the platelete
aggregasion
 RALES trial and REMINDER were also
trial to evaluate the efficacy of potassium
channel inhibitors

3. Study design
 Drug Given: Eplirenone 50 mg od
 Included
 Within 3 -14 days post MI
 LVD EF<40 % by either echo. LV angio
 Presnce of evidence of LVD
Rales on auscultation
Cxr findings
3rd heart sound
Diabetic pts included donot have the symptoms
Excluded
 Potassium conc: > 5.0 meq/dl
 Creatinine > 2.5 mg/dl

4. Eplerenone
(n = 3,313)
Placebo
(n = 3,319)
Endpoints (at mean of 16 month follow-up):
 Primary – 1) death from any cause and 2) death or
hospitalization from CV causes
EPHESUS Trial
N Engl J Med 2003;348:1309-
Optimal medical therapy
(ACE inhibitors, angiotensin-receptor blockers, diuretics, and beta-
blockers, coronary reperfusion therapy)
6,632 patients with acute MI complicated
by heart failure and systolic left
ventricular dysfunction
 Acute MI in prior 3-14 days
 Left ventricular dysfunction (EF <40%)
 symptoms (in non-diabetics but not required for diabetics)

6. Results
 Reduces all cause mortality (14.4 v/s
16.7%) NT=50
 Reduces mortality from CV
cause(NT=33) or hospitalization from
CV cause
 15% relative reduction of
hospitalization due to Heart failure in
Eplerenone group V/s Placebo
 Risk of seroius hyperkalemia was inc:
when cr:cl< 50

7. EPHESUS Trial: Primary Endpoints
14.4%
16.7%
0%
5%
10%
15%
20%
All-cause
Mortality
RR 0.85
p=0.008
26.7%
30.0%
0%
10%
20%
30%
40%
CV Death or
Hospitalization
RR 0.83
p=0.005
Eplerenone Placebo
N Engl J Med 2003;348:1309-
Eplerenone Placebo

8. EPHESUS Trial: Secondary Endpoint
12.3%
14.6%
0%
5%
10%
15%
20%
CV Death
RR 0.87
p=0.002
N Engl J Med 2003;348:1309-
Eplerenone Placebo

10. EPHESUS Trial: Serious Adverse Events
5.5%
3.9%
0%
2%
4%
6%
8%
Serious
hyperkalemia
p=0.002
0.5%
0.6%
0.0%
0.5%
1.0%
1.5%
Gynecomastia
p=0.70
Eplerenone Placebo
N Engl J Med 2003;348:1309-
Eplerenone Placebo

11. Conclusion
 Addition of Eplirinone to Maximal therapy
reduces all cause mortality and mortality
from CVD and rehospitalization from
CVD in Pts with MI complicated by LVD.
 Eplirinone reduces CVD mortality by
15%
 Majority of them were due dec: in
sudden death
 Risk of serious hypokalemia was twicwe
greater in placebo than risk of
hyperkalemia ineplirenone group