This document discusses heart failure, its causes, symptoms, and treatments. It notes that heart failure is a growing concern, with more than 20 million cases worldwide. While treatments like diuretics, ACE inhibitors, and beta blockers are used, aldosterone levels remain high in many patients. The document examines the role of the aldosterone antagonist eplerenone in improving outcomes for heart failure and resistant hypertension patients when added to standard therapy. Clinical trials demonstrate eplerenone reduces mortality, hospitalizations, and blood pressure more effectively than other aldosterone antagonists.

1. ~50
The Burden of the Heart
DIE WITHIN
5 YEARS
OF
DIAGNOSIS
Gerber et al. JAMA Intern Med 2015;175:996-1004 and Zarrinkoub et al. European Journal of Heart Failure 2013;15: 995–1002

2. The Burden of the Heart
Gerber et al. JAMA Intern Med 2015;175:996-1004.
1IN4OF HEART FAILURE PATIENTS
DIE WITHIN 1 YEAR
OF DIAGNOSIS1

3. The Burden of the Heart
Gerber et al. JAMA Intern Med 2015;175:996-1004.
~45OF CARDIOVASCULAR EVENTS
ARE DUE TO HEART FALIURE

4. HEART FAILURE: A GROWING CONCERN
 More than 20 million people have heart failure worldwide.1
1.Mann DL, Chakinala M (2012). Harrison's principles of internal medicine: Chapter 234. Heart Failure and Cor Pulmonale. (18th ed.).
New York: McGraw-Hil
INCIDENCE INCREASING DUE TO INCREASED PREVALENCE OF RISK FACTORS
 HYPRETENSION
 DIABETES
 DYSLIPIDEMIA
 OBESITY
One in five adults at age 40 will develop heart failure during their lifetime
HF carries substantial morbidity and mortality

5. HEART FAILURE
 Heart cannot pump enough blood to meet the body's needs.
CAUSES
 HYPERTENSION
 CORONARY ARTERY DISEASE
 MYOCARDIAL INFRACTION

6. Heart Failure:Classification based on type
CLASSIFICATION
SYSTOLIC
EJECTION
FRACTION <40%
HEART CANNOT
PUMP OUT
BLOOD
DIASTOLIC
EJECTION
FRACTION IS
NORMAL
VENTRICLES
CANNOT RELAX
PROPERLY
LONG STANDING CHF HAVE BOTH SYSTOLIC & DIASTOLIC DYSFUNCTION

7. Link between Hypertension & Heart Failure
HYPERTENSION
L.V AFTERLOAD
HIGH
L.V CONTRACTS
WITH MORE FORCE
L.V H
L.V MUSCLE STIFF
L.V UNABLE TO PUMP
BLOOD TO BODY
LOW BLOOD
SUPPLY ACTIVATES
RAAS
INCREASE IN
BLOOD VOLUME
FLUID ACCUMULATION
IN LUNGS,LEGS
SYSTOLIC HF

8. Link between Atherosclerosis & Heart Failure
ATHEROSCLEROSIS
LACK
OF BLOOD SUPPLY
TO HEART MUSCLE
DAMAGE TO
HEART MUSCLE
L.V UNABLE TO PUMP
BLOOD TO BODY
LOW BLOOD
SUPPLY ACTIVATES
RAAS
INCREASE IN
BLOOD VOLUME
FLUID ACCUMULATION
IN LUNGS,LEGS
SYSTOLIC HF

9. SYMPTOMS OF HEART FAILURE

10. HEART FAILURE: CLASSES BASED ON PATIENT SYMPTOM

11. TREATMENT GOALS
 Treat the underlying cause
 Manage symptoms
 Increasing life span
 Improve quality of life

12. HEART FAILURE: MANAGEMENT
Diuretics
ACE Inhibitors
ARB's
Aldosterone
Antagonist
β Blockers
Mobilizing
Fluid
Given in all
stages of HF
Intolerant to
ACE inhibitors
Plasma aldosterone levels are elevatd in HF patients.1
1. Thomas H. Hostetter et.al:Aldosterone in Chronic Kidney and Cardiac Disease.JASN September 1, 2003 vol. 14 no. 9 2395-2401
Mild to
moderate CHF
as an ajuvant

13. Diuretics in HF
 Reduces fluid accumulation in HF patients
 Most preferred class are Loop Diuretics
DRAWBACKS
 Do not treat the high aldosterone levels
 Chronic use of diuretic leads to intolerance to diuretics
 Chronic use of loop diuretic leads to hypokalemia thus icreasing chances of cardiac death.
For Chronic use ideally should be given with aldosterone antagonist

14. ACE Inhibitors in HF
 Used in all class of heart failure
 Reduces the aldosterone level in short term.
DRAWBACKS
 Long term use not effective in controlling aldosterone levels.
 Cough & Angioedema in patients
Aldosterone Antagonist are added to the therapy to control aldosterone levels.

15. β Blockers in HF
 β Blockers are used in Class II-III HF Patients.
 Used as an adjuvamt with ACE inhibitors/ARB's
 Reduces Ventricular Stress & plasma renin levels
DRAWBACKS
 No Action on aldosterone Levels
 Provide symptomatic relief
 No use in severe cases.
To Tackle aldosterone levels, aldosterone antagonist may be used as adjuvant

16. Importance of aldosterone in HF patients
 Plasma aldosterone levels are elevated in HF patients.1
1. Thomas H. Hostetter et.al:Aldosterone in Chronic Kidney and Cardiac Disease.JASN September 1, 2003 vol. 14 no. 9 2395-2401
2.Schirpenbach, C; Reincke, M (March 2007). "Primary aldosteronism: current knowledge and controversies in Conn's syndrome.". Nature clinical practice.
Endocrinology & metabolism. 3 (3): 220–7
 Reabsorption of sodium in exchange for pottassium
 Increasing the blood volume
 Increasing the blood pressure
 10% of people with high blood pressure have high aldosterone levels.2
Aldosterone causes

18. Eplerenone
Catagory: Pottassium Sparing Diuretic
 Indication
 As an adjuvant with ACE
inhibitors/ARB,Beta Blockers in heart
Failure
 Adjuvant in treatment of resistant
hypertension
 Dosage
 Epleronone 25mg OD. Titrated upto
50mg OD within 4 weeks
ESC 2016 Guideline:
“Level of recommendation A, is given to MRAs for
patients with HFrEF, who remain symptomatic despite
treatment with an ACE-inhibitor and a beta-blocker
and have an LVEF below 35 %.”

19. Eplerenone : Mechanism of action
Prevent reabsorption of
sodium in exchange of
pottasium
Reduces blood volume

20. Eplerenone vs Spironolacone
PARAMETER EPLERENONE SPIRONOLACTONE
ALDOSTERONE RECPETOR More selective towards Aldosterone
receptor
Less selective comapred to Eplerenone
PROGESTERONE,ANDROGEN
RECEPTOR
Lower affinity More affinity comapred to Elperenone
Less chance of sexual side effects like gynaecomastia in males & menstrual disturbances in females with
Eplerenone
Source: Allan Struthers et.al:A Comparison of the Aldosterone-blocking Agents Eplerenone and Spironolactone. Clin. Cardiol. 31, 4, 153–158 (2008)
Well tolerated compared to Spironolactone

21. Eplerenone Pharmacokinetics
Bioavailability: 70%
Protein Binding: 50%
Half Life: 4-6 hours
Excretion: Urine 67% Feces 32%

22. Adverse effect & Contraindication
 Common adverse drug reactions associated with the use of
eplerenone include: hyperkalaemia, hypotension, dizziness,
altered renal function
 Eplerenone is contraindicated in patients with
 hyperkalaemia: serum pottasium >5 mmol/L
 severe renal impairment
 severe hepatic impairment
 Use with other Pottassium sparing diuretic
 Type 2 diabetes with microalbuminuria

23. Drug interaction
 Primarily metabolised by the cytochrome P450
 Use with ketoconazole and itraconazole erythromycin, saquinavir,
and verapamil is contraindicated.
 Potassium supplements and other potassium-sparing diuretics
use may increase the risk of hyperkalaemia

24. EPHESUS TRIAL:Post-myocardial infarction heart failure
Aim: To demostrate Eplerenone reduces cardiovascular mortality or hospitalization in patients with acute
myocardial infarction and heart failure who are receiving optimal medical therapy.
Methodology:
6642 patients enrolled with MI & EF<40%. 3319 patients receive eplerenone & 3313 patients received placebo as
an adjuvant with standard treatment option for 16 months.Patients received the drug 3-14 days post MI
Result:
There was a reduction of 15 percent in the risk of hospitalization for heart failure with eplerenone compared to
placebo
13 percent reduction in hospitilazation due to CV events compared to placebo
Bertram Pitt et.al:Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction.N Engl J Med
2003; 348:1309-1321

25. EMPHASIS-HF
Aim:
The effect of eplerenone when added to standard therapy on clinical outcomes was investigated in patients with systolic
heart failure and mild symptoms (NYHA functional class II)
Methodology:
2737 patients NYHA class II heart failure and an EF <= 35% were randomized to the treatment with Eplerenone or
placebo for 1.8 years
Result:
24% reduction in cardiovascular death & 42% reduction in hospitilazation with eplerenone compared to placebo
Reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild
symptoms.

26. Resistant Hypertension
 Failure to reach the target BP despite use of 3 antihypertensive agents of
different classes one of which is diuretic
 Hyperaldosteronism is particularly common in patients with resistant
hypertension.1
 Aldosterone receptor may be used as an adjuvant therapy in resistant
hypertension.2
1.Maria Czarina Acelajado et.al:Aldosteronism and Resistant Hypertension. International Journal of Hypertension Volume 2011 (2011)
2. Calhoun DA: Hyperaldosteronism as a common cause of resistant hypertension. Annu Rev Med.2013;64:233-47

27. Eplerenone in resistant hypertension
Aim:
To investigate the blood pressure (BP)–lowering ability of eplerenone in resistant hypertensive patients
Methodology:
57 resistant hypertensive patients whose home BP was ≥135/85 mm Hg were investigated.
The patients were randomized to either an eplerenone group or a control group and followed for 12 weeks
Result:
Greater reduction in SBP compared to placebo

28. Eplerenone in resistant hypertension
Result:
Greater reduction in DBP
compared to placebo
Eguchi K et.al:Add-On Use of Eplerenone Is Effective for Lowering Home and Ambulatory Blood Pressure in Drug-Resistant Hypertension.J
Clin Hypertens (Greenwich). 2016 Jun 13

29. Eplerenone vs Spironolactone in resitant Hypertension
Aim:
To access the efficacy, safety, and tolerability of eplerenone hypertensive patients compared to
spironolactone
Methodology:
417 patients were randomized to Spironolactone and Eplerenone
24 hours BP monitering was carried out.
Result:
Eplerenone (100 mg) reduced BP by 75% compared with spironolactone 100 mg
No antiandrogenic or progestational effects were observed in eplerenone-treated patients
Weinberger MH et.al:Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension.Am J Hypertens. 2002 Aug;15(8):709-16.

30. Eplerenone reverses spironolactone-induced gynaecomastia
Aim:
To investigate the efficacy and safety of aldosterone antagonist, eplerenone in the treatment of
spironolactone-induced painful gynaecomastia
Methodology:
 19 patients with cirrhosis had been administered spironolactone and suffered from
gynaecomastia, have been included in the study
 Substitution of spironolactone with eplerenone was followed for 3 months
Result:
All 19 patients reported regression of gynaecomastia & pain associated with gynaecomastia
Georgios Dimitriadis et.al:Eplerenone reverses spironolactone-induced painful gynaecomastia in cirrhotics.Hepatol Int. 2011 Jun; 5(2): 738–739.

31. Eplerenone at a glance
offers
 Lower affinity for androgen, progesterone receptor
 Minimizing risk of gynaecomastia in males & menstrual disorder in females
 Reduced hospital stay
 Reduced mortality in NYHA class II patients
 More potent in reducing BP compared to spironolactone
 Allevates pain & regresses gynaecomastia in males.