HF Univ Abraham Pharmacologica Rx

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Pharmacologic Treatmentof Chronic Heart
Failure William T. Abraham, MD, FACP,
FACC Professor of Medicine Chief, Division of
Cardiovascular Medicine Associate Director, Davis
Heart Lung Research Institute The Ohio State
University Columbus, Ohio
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Goals of Heart Failure Therapyin the Symptomatic
Patient

• Relieve HF symptoms
• i.e., make patients feel better
• Improve overall clinical status
• Stabilize acute episodes of decompensation
• Decrease morbidity and mortality
• Slow and/or reverse disease progression
• Identify and treat reversible causes ofLV
  dysfunction

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How Do We Make Heart Failure Patients Feel Better?

• With hemodynamic interventions
• Diuretics
• Digoxin
• Vasodilators
• Positive inotropic agents
• Mechanical interventions that improve
  hemodynamics (e.g., CRT, LVADs)

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How Do We Make Heart Failure Patients Live Longer?

• With neurohormonal interventions
• ACE inhibitors
• Angiotensin receptor antagonists(in
  ACE-inhibitor intolerant patients)
• Aldosterone antagonists
• Beta-Blockers
• And with
• Mechanical interventions that improve LV
  remodeling (e.g., CRT, LVADs)

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The CV Disease Continuum
Remote Myocardial Infarction
Recent Myocardial Infarction
Post-MI LVD With Symptoms
Post-MI LVD Without Symptoms
Mild CHF
Moderate CHF
Severe CHF
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Neurohormonal Blockade Across the CV Disease
Continuum
? Angiotensin II (Renin-Angiotensin System RAS)
? Norepinephrine (Sympathetic Nervous System
SNS)
RAS Inhibition
?-Blockade
Disease Progression
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Neurohormonal Blockade Across the CV Disease
Continuum
? Angiotensin II (Renin-Angiotensin System RAS)
? Norepinephrine (Sympathetic Nervous System
SNS)
RAS Inhibition
?-Blockade
Disease Progression
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Deleterious Effects of Angiotensin II in CV
Disease

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Effect of ACE Inhibitors on Mortality Reduction
in Patients With LVD or Heart Failure
Garg R et al. JAMA. 1995 2731450-1456.
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Neurohormonal Interventions Across the Continuum
Moderate CHF
Severe CHF
Mild CHF
Post-MI LV dysfunction
SOLVD Treatment (enalapril)
CONSENSUS (enalapril)
AIRE/SAVE/TRACE (ramipril/captopril/ trandolapril)
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ACC/AHA Guidelines for the Evaluation and the
Management of Chronic Heart Failure in the Adult
Hunt SA et al. J Am Coll Cardiol.
2001382101-2113..
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Angiotensin Receptor Blockade inMild to Moderate
Heart Failure
CHARM and Val-HeFT Trials Addition of
candesartan or valsartan to ACE inhibitor and
b-blocker in class II-III heart failure 0-10
lower risk of death (P 0.05) 13-15 lower
risk of death or hospitalization for heart
failure in both trials, both P risk of hypotension, renal insufficiency and
hyperkalemia with ARB treatment
Cohn JN et al. N Engl J Med. 20013451667-1675
Pfeffer MA et al. Lancet. 2003362759-766
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VALIANT ACE Inhibitor, Angiotensin Receptor
Blocker, or Both in Post-MI LVD
Pfeffer MA et al. N Engl J Med.
20033491893-1906.
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Neurohormonal Interventions Across the Continuum
Moderate CHF
Severe CHF
Post-MI LV dysfunction
Mild CHF
SOLVD Treatment (enalapril)
CONSENSUS (enalapril)
AIRE/SAVE/TRACE (ramipril/captopril/ trandolapril)
CHARM/Val-HeFT (candesartan/valsartan)
?

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Trials with Aldosterone Blockade
Pitt B et al. N Engl J Med. 1999341709-717. Pitt
B et al. N Engl J Med .20033481309-1321.
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Neurohormonal Interventions Across the Continuum
Moderate CHF
Severe CHF
Post-MI LV dysfunction
Mild CHF
SOLVD Treatment (enalapril)
CONSENSUS (enalapril)
AIRE/SAVE/TRACE (ramipril/captopril/ trandolapril)
RALES (spironolactone)
EPHESUS (eplerenone)
?
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Neurohormonal Blockade Across the CV Disease
Continuum
? Angiotensin II (Renin-Angiotensin System RAS)
? Norepinephrine (Sympathetic Nervous System
SNS)
RAS Inhibition
?-Blockade
Disease Progression
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Deleterious Effects of Norepinephrinein CV
Disease
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Effect of ?-Blockade on Outcome in Patients With
Heart Failure and Post-MI LVD
Target HF Dosage Study Drug Severity
(mg/day) Outcome US Carvedilol1 Carvedilol
Mild/ 6.25 to 25 ?48 disease progression mode
rate bid (P.001) CIBIS-II2 Bisoprolol
Moderate/ 10 qd ?34 mortality severe (P) MERIT-HF3 Metoprolol Mild/ 200 qd ?34
mortality succinate moderate (P.0062) CO
PERNICUS4 Carvedilol Severe 25 bid ?35
mortality (P.0014) CAPRICORN5
Carvedilol Post-MI LVD 25 bid
?23 mortality
(P.031)
1Colucci WS et al. Circulation.
19969428002806. 2CIBIS II Investigators and
Committees. Lancet. 1999353913. 3MERIT-HF
Study Group. Lancet. 199935320012007. 4Packer
M et al. N Engl J Med. 200134416511658. 5The
CAPRICORN Investigators. Lancet.
200135713851390.
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Neurohormonal InterventionsAcross the Continuum
Moderate CHF
Severe CHF
Mild CHF
Post-MI LV dysfunction
SOLVD Treatment (enalapril)
CONSENSUS (enalapril)
AIRE/SAVE/TRACE (ramipril/captopril/ trandolapril)
US Carvedilol Trials (carvedilol) MERIT-HF (metopr
olol) CIBIS II (bisoprolol)
COPERNICUS (carvedilol)
CAPRICORN (carvedilol)
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ACC/AHA Guidelines for the Evaluation and
Management of Chronic Heart Failure in the Adult
Hunt SA et al. J Am Coll Cardiol.
20013821012113.
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Neurohormonal InterventionsAcross the Continuum
Moderate CHF
Severe CHF
Post-MI LV dysfunction
Mild CHF
SOLVD Treatment (enalapril)
CONSENSUS (enalapril)
AIRE/SAVE (ramipril/captopril)
US Carvedilol/MERIT (carvedilol/metoprolol)
COPERNICUS (carvedilol)
CAPRICORN (carvedilol)
RALES (spironolactone)
EPHESUS (eplerenone)
CHARM/Val-HeFT (candesartan/valsartan)
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Evidence-Based Treatment Across the Continuum of
LVD and Heart Failure
Reduce Mortality
Control Volume
Aldo Ant or ARB
Diuretics
?-blocker
ACEI
Digoxin
Treat residual symptoms
Cardiac Resynchronization with/without ICD
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Diastolic Heart Failure Diagnosis
1. Signs and symptoms of CHF 2. Normal LV
ejection fraction 3. Measurement of diastolic
function is confirmatory but not mandatory
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Pathophysiology ofDiastolic Heart Failure
Normal
Diastolic Dysfunction
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(mmHg)
LV Diastolic Pressure
LV Diastolic Volume (mL)
28
(mmHg)
13 mmHg
20 mL
LV Diastolic Pressure
2 mmHg
20 mL
LV Diastolic Volume (mL)