Eplerenone, a Selective

Aldosterone Blocker, in Patients

with Left Ventricular Dysfunction

after Myocardial Infarction

(EPHEUSIS Trial)

By

Dr Salman Ahmed

Introduction

Aim to evaluate the effect of eplerononein 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 plateleteaggregasion

RALES trial and REMINDER were also trial to evaluate the efficacy of potassium channel inhibitors

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

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;348:1309-21

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)

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

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;348:1309-21

Eplerenone Placebo

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;348:1309-21

Eplerenone Placebo

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;348:1309-21

Eplerenone Placebo

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 twicwegreater in placebo than risk of hyperkalemia ineplirenone group