Download Congestive Heart Failure

A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Objectives for Pharmacists
A Comprehensive Overview of
Congestive Heart Failure
PGY1 Pharmacy Practice Residents
Mission Hospital
2010
• Define heart failure (HF) and the staging classification
• Discuss pathophysiology and risk factors
• Describe treatment options for acute management of HF
exacerbations
• Discuss non-pharmacological therapies of HF
• Recognize pharmacological categories to treat HF
• Determine appropriate management based on stages of HF
• Describe the role of the pharmacist in the management of
HF
Objectives for Technicians
• Define heart failure
• Discuss the pathophysiology and risk factors
• Recognize treatment options for acute
management of HF exacerbations
• Review non-pharmacological therapies of HF
• Recognize pharmacological categories to treat
HF
Epidemiology &
Pathophysiology
Wesley Dulaney, PharmD
Epidemiology 1,2
• Approximately 5.8 million people have HF
in the US
• Approximately 670,000 people are
diagnosed with HF each year
• 1 in 5 people die within 1 year of HF
diagnosis
• Estimated total costs for HF in 2010: $40
billion
Normal Functioning Heart 3,4
• Systole
– Ventricles contract and
pump blood to the body
• Diastole
– Ventricles relax and fill
with blood

Ejection fraction (EF)
www.mayoclinic.com
› Percent of blood ejected from the heart with each
ventricular contraction
› Normal ejection fraction: 55%- 70%
1
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Definition 3,4,5
Types of HF 3,5,6
• Left-sided
• Heart failure
Clinical syndrome that can result from a
structural or functional cardiac disorder
that impairs the ability of the ventricle to
fill with or eject blood
Types of HF 3,5,6
• Right-sided
– Left ventricle cannot adequately pump
oxygen-rich blood to the rest of the body
(peripheral tissues and organs)
– Causes blood and fluid to back up into the
lungs
Types of CV Dysfunction 3,6
• Systolic dysfunction
– Right ventricle cannot adequately pump
oxygen-depleted blood through the
pulmonary vessels
– Causes blood to back up in the veins and
fluid to accumulate in the legs, feet, and
abdomen
–Impaired ventricular contraction and
pumping
• Diastolic dysfunction
–Impaired ventricular relaxation and
filling
– Usually develops as a result of left-sided HF
Pathophysiology 3,7
Myocardial contractility
Compensatory Mechanisms 3,7
• Adrenergic system
– Increases myocardial contractility
Cardiac output
Compensatory mechanisms activated
– Tachycardia
– Increases sodium and fluid retention
– Activates the renin-angiotensinaldosterone system (RAAS)
2
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Compensatory Mechanisms 3,7
• Renin-angiotensin-aldosterone system
– Vasoconstriction
• Redirection of blood flow
– Fluid retention
Compensatory Mechanisms 3,7
• Long-term compensation leads to:
–Further reduction of cardiac function
–Cardiac remodeling
• Other mechanisms
– Frank-Starling mechanism
– Bowdith effect
Cardiac Remodeling 3,7
5
• Systolic dysfunction
– Ventricular muscle continues to overstretch
attempting to increase myocardial
contractility
– Over time, the ventricle enlarges and
ventricular wall thins
– Dysfunction: impaired ventricular
contraction and pumping of blood
– EF < 40%
Medmovie.com from the AHA
Cardiac Remodeling 3,7
Ventricular Hypertrophy 5
• Diastolic dysfunction
– Ventricular muscle enlarges because of
overstimulation (“hypertrophy”)
– Ventricular muscle and wall becomes stiff and
rigid
– Dysfunction: impaired ventricular relaxation
and filling
– EF > 50%
• “Preserved EF”
Medmovie.com from the AHA
3
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Causes 3,5,8
Causes 3,5,8
• Coronary artery disease (CAD)
• Cardiomyopathy
• Hypertension
• Alcohol
• Diabetes
• Valvular disease
• Damage caused by
• Thyroid disorders
an MI
AHA
• Arrhythmias
Medmovie.com from the AHA
• Congenital heart defects
AHA
Risk Factors 1,3,5,6
Incidence by Age and Gender
1
• Age
– Incidence doubles for each successive
decade of life after 40
• Gender
– Male > Female
• Race
– Greatest for African Americans
• Obesity
• Smoking
Signs and Symptoms 3,5,6
• Dyspnea
Signs and Symptoms 3,5,6
• Edema
– On exertion
– Feet and ankles
– Orthopnea
– Abdomen
– Paroxysmal nocturnal
– Jugular venous distention
• Cough
– Pulmonary
• Pulmonary rales
• Tachycardia
• Exercise intolerance
• Fatigue
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A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
NYHA Classification 3,9
HF Categorization
• New York Heart Association (NYHA)
Classification
• American College of Cardiology/American
Heart Association (ACC/AHA) Staging
ACC/AHA Staging 3,9
Stage
Description
A
No structural heart disease but has
significant CV risk factors
B
Structural heart disease but without signs
or symptoms of HF
C
Structural heart disease with prior or
current symptoms of HF
D
Refractory HF requiring specialized
interventions
Class
Symptoms/Limitations
I
No symptoms and no limitation in ordinary
physical activity
II
Mild symptoms and slight limitation during
ordinary activity
III
Marked limitation in activity due to
symptoms, even during less-than-ordinary
activity. Comfortable at rest
IV
Severe limitations. Experiences symptoms
even while at rest
Case
JD is a 65 yo male who presents to his PCP for a
routine check-up . He was diagnosed with leftsided, systolic heart failure 10 years ago. He also
has a h/o HTN, CAD, and hyperlipidemia. In May of
2010, JD experienced severe SOB, fatigue, and
swelling of his feet and ankles, for which he was
hospitalized and treated. He states today that he
has no current symptoms but has noticed that he
can only make it 3/4 of the way to the mail box
before stopping to rest.
Case
1. Using the NYHA classification, how would you
classify JD’s heart failure?
a)
b)
c)
d)
Class I
Class II
Class III
Class IV
2. Using the ACC/AHA staging, how would you classify
JD’s heart failure?
1.
2.
3.
4.
Non-pharmacological Therapies and
Prevention
Annette Sajecki, PharmD
Stage A
Stage B
Stage C
Stage D
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A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Non-Pharmacologic Management
• Recognize the role of self-management
• Lifestyle modifications are difficult to sustain and
require a lot of support in practice
• Patients should be encouraged to self-monitor
• Drugs alone will not achieve the best outcome
• Non-pharmacological measures are implemented
in parallel with drug treatment
Patient Education
• 40-59% of readmissions could be avoided
– Non-pharmacologic treatment
• Non-pharmacological treatment combined with
pharmacological treatment can help improve
morbidity and mortality
– Stability
– Functional capacity
– Quality of life
Diet and Nutrition 10,11,12
• Diet and nutrition
• Fresh fruits and vegetables
• Lifestyle modifications
• Whole grains
• Risk factor reduction
• Lean meats
• Rest and exercise
• Low fat dairy products
• Self-weighing
• Rosemary, dill, lemon, pepper, onion, garlic
• Avoidance of certain medications
• Non-compliance
Diet and Nutrition 10,11,12
• Ensure adequate general nutrition
– Minimize cardiac cachexia
– Independent risk factor for mortality
• Weight reduction
– Physical activity and dietary modification
Sodium Restriction 10,11,12
• American diet
– Sodium: 3-6 grams
• Limit salt intake
– Sodium: 2 grams
– No randomized studies
• Avoid foods that are processed and that are
naturally high in sodium
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A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Sodium Restriction 10,11,12
• Table salt should not be added to food
High Sodium Containing Foods 12
Hot dogs, Bologna, Ham, Salami
Cheese
– 1 teaspoon = 2.4 grams sodium
Salted Snack Foods (salted nuts, salted pretzels, potato
chips, tortilla chips)
• Salt substitutes
– May contain potassium
Condiments (ketchup, soy sauce, Worcestershire sauce)
• May be challenging for many patients
Canned soup and vegetables
V8 juice
Gatorade, Diet Coke
Pickled foods
Lifestyle Modifications 11,12,13
• Alcohol consumption
• Smoking
– Alcohol induced
cardiomyopathy
– Mortality rate 40%
– Other forms of heart
failure
– Increases heart rate and
blood pressure
• Advise moderate
alcohol
consumption
• Cardioprotective or
cardiotoxic?
– Reduces cardiac output
– Increases oxygen
demand and decreases
myocardial oxygen
supply
Risk Factor Reduction 11,12
• Immunizations
– Influenza
– Pneumococcal
• One time vaccination
• If <65 years of age, booster vaccine
recommended 5 years after initial
vaccination
• Stress Reduction
Risk Factor Reduction 11,12,15,16
• Blood Pressure
– JNC-7 Guidelines
• <140/90 mmHg
• <130/80 mmHg: CKD,
CAD, PAD, AAA, angina,
MI
• <120/80 mmHg: Left
ventricular dysfunction
• Cholesterol
– NCEP/ATP III Guidelines
• LDL < 100
• HDL >40 (males), >50
(females)
• TG <150
• TC < 200
– High blood cholesterol
levels linked to coronary
artery disease
Rest and Exercise 11,12
• Exercise tolerance
• Cardiac rehabilitation programs
• Benefits
– Symptoms
– Functional capacity
– Greater sense of wellbeing
7
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Rest and Exercise 11,12
• Stable heart failure
– Regular low intensity physical activity
– Prevent atrophy of the heart
– Prevents progressions of heart failure
Self-weighing 12
• Patients should monitor their weight daily
– Same time of day
– Same scale
– Same amount of clothes
• Acute heart failure
– Bed rest is recommended to ease cardiac
workload
– Elevate feet and wear support stockings
Weight Chart
Date
Weight
Comments (symptoms, concerns
etc.)
• Weight gain of 2-3 pounds in a single day
– Fluid retention
– Self adjustment of diuretic dose
Drugs to Avoid or Use with Caution 13
• Nonsteroidal antiinflammatory drugs
• Anthracyclines
• Corticosteroids
• Tratuzumab
– Cardiotoxins
– Sodium and water
retention
• Calcium channel
antagonists
– Neurohormonal
activation
Drugs to Avoid or Use with
Caution 13
• Goody’s Powder
• Timentin
• Zosyn
– High sodium content
• Metformin
– Lactic acidosis
• Black box warning
• Pregabalin
– Peripheral and
pulmonary edema
• Cilostazol
– Ventricular arrhythmias
• Cyclophosphamide
• Dronedarone
– Induces exacerbation
• Minoxidil
• Thiazolidinediones
– Fluid retention
Non-compliance 12,14
• Related to acute exacerbations and poor
prognosis
• Adherence should be emphasized
– Clinician involvement
• Reduces hospitalizations
• Patients should understand their medication
regimens
– Importance of medications
– Proper administration
– Adverse effects
8
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Compliance with non-pharmacological
recommendations and outcome in HF patients 14
Van der Wal M et al. Compliance with nonpharmacological recommendations and
outcome in heart failure (HF) patients.
European Heart Journal. 2010;31:14861493.
• Prospective, randomized, multi-center study
• Adult patients who had been hospitalized for an
acute symptomatic HF exacerbation (n = 830)
• Primary Outcome
– HF hospitalization or death from any cause
– Number of unfavorable days
• The number of days the patient was hospitalized for
HF or death during the 18 month follow-up period
Results 14
• Compliance with non-pharmacological
recommendations
– 48% of patients were compliant with all four nonpharmacologic recommendations (non-rx)
• Relation between compliance and mortality or
heart failure hospitalization
– Patients who were non-compliant with the nonrx regimen had an increased risk for death or HF
hospitalization
Results 14
• Unfavorable days
– Patients who were non-compliant with the nonrx regimen had more unfavorable days than
compliant patients
• p<0.01*
• Conclusion
– Non-compliance with non-pharmacological
recommendations is associated with adverse
outcomes
• p=0.01*
• JD has an office visit with his PCP. He has had a
recent heart failure exacerbation which required
admission to the hospital. He states that he has
had frequent migraines (1-2 times per week) in
which he uses Goody's Powder or Excedrin. He
also states that he has been trying to eat a more
healthy diet in which he eats more fruits and
vegetables seasoned with Mrs. Dash seasoning.
JD also drinks Gatorade, sweet tea and V8 juice.
1. Which of the following product lists can
exacerbate heart failure?
a) Goody's powder, Excedrin, Gatorade, Mrs. Dash
seasoning
b) Goody's powder, Gatorade, V8 juice, Mrs. Dash
seasoning
c) V8 juice, Gatorade, Goody's powder
d) V8 juice, Gatorade, Goody's powder, Sweet Tea
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A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Case
Acute Management of CHF
Lyndsey Hogg, PharmD
• JD presents to the emergency department with
complaints of cough and SOB at rest. He states that
he has been unusually tired over the past few days
and has gained 10 pounds during that period. Upon
admission, his vitals are as follows:
– HR 90
– BP 185/95
– O2 sat 95%
BNP is 874 pg/mL.
Causes of Decompensation
• Medication/dietary non-compliance
• Medications
• Disease progression
• Co-morbid diseases
• Stress
B-type Natriuretic Peptide
• Neurohormone
• Useful in differential diagnosis of dyspnea
• Abnormal if >100-150 pg/ml
Clinical Presentation
• Shortness of breath, tachypnea, diaphragmatic
breathing
• Weight gain
• Dramatic fatigue, symptoms at rest
• Obtunded/confused
• Worsening hemodynamics
• Abnormal blood pressure &/or heart rate
• Cardiogenic shock
Goals of Therapy 17,18
• Relief of symptoms
• Identify etiology & precipitating factors
• Improve hemodynamic profile
• Optimize chronic oral therapy
• Minimize side effects
• Educate patients
10
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Approaches to Treatment 17
Hemodynamic Profiling 17
• “Wet” vs “Dry” heart failure
• Clinical parameters
– Signs/symptoms, BP, renal function
• Invasive hemodynamic monitoring
– Not routinely recommended
• Can help determine course of treatment
• Helps rapidly assess results of an
intervention
Cardiac index (L/min/m2)
Forrester Classification 17
Subset II
(pulmonary
congestion)
Subset I
(normal)
2.2
Subset IV
(pulmonary
congestion &
hypoperfusion)
Subset III
(hypoperfusion)
18
Pulmonary artery occulsion pressure (mm Hg)
Loop Diuretics 17,19,20
• Furosemide, bumetanide, torsemide
• Place in therapy
– Pulmonary congestion
• MOA
– Decrease preload
Medications
• Diuretics
• Positive inotropic agents
– Dobutamine
– Milrinone
– Dopamine
• Vasodilators
– Nitroprusside
– Nitroglycerine
– Nesiritide
Loop Diuretics 19,20
• Contraindicated with sulfa allergy
• Adverse effects
– Electrolyte abnormalities
– Hypotension
– Renal dysfunction
– Ototoxicity
• Monitoring
– Renal function
– BP
– Basic metabolic panel (BMP)
11
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Diuretic Resistance 17
• Prolonged absorption
• Lower peak concentrations
• Increased ability to reabsorb sodium
• Low cardiac output
Positive Inotropic Agents 19,20
• Adverse effects
– Ventricular arrhythmias
• Monitoring
Positive Inotropic Agents 17,18,20
• Dobutamine, milrinone, dopamine
• Place in therapy
– Hypoperfusion +/- pulmonary congestion
– Reserved for patients with refractory
symptoms
• MOA
– Increase cardiac contractility  increased
cardiac output  increased perfusion
Positive Inotropic Agents 17,19,20
• Dobutamine
– Synthetic catecholamine
• Increases cardiac contractility
– Telemetry
• Vasodilatory effects
– HF symptoms
• Little effect on mean arterial pressure
– Electrolytes
• Improves coronary blood flow
• Increased mortality rates
Positive Inotropic Agents 17,19,20
• Dobutamine
– Dose
• Initial 2.5-5 mcg/kg/min (titrate to effect)
• Max 40 mcg/kg/min
– “Bridge” therapy for patients awaiting
transplant
Positive Inotropic Agents 17,19,20
• Milrinone
– Phosphodiesterase (PDE) III inhibitor
• Increases cardiac contractility
• Arterial & venous vasodilatory effects
– Dose
• Loading: 50 mcg/kg
• Maintenance: 0.375-0.75 mcg/kg/min
• Renal impairment requires lower dose
– Monitor BP & CBC
12
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Vasodilators 17,18
Positive Inotropic Agents 19,20
• Dopamine
– Endogenous catecholamine
– Generally avoid in ADHF unless:
• Marked systemic hypotension
• Cardiogenic shock
– Dose
• Initial: 1-5 mcg/kg/min (titrate to effect)
• Max: 50 mcg/kg/min
– Actions are dose-dependent
• Nitroprusside, nitroglycerine, nesiritide
• Place in therapy
– Adjunct to diuretics for pulmonary congestion
+/- severe hypertension
• MOA
– Decrease vascular resistance
Vasodilators 19,20
• Nitroprusside
– Mixed arterial-venous vasodilator
• Reduces preload and afterload
– Adverse effects
• Hypotension (dose-limiting)
• Headache
– Initial dose: 0.3-0.5 mcg/kg/min (titrate to
effect)
– No effect on survival
Vasodilators 17,19,20
• Nitroglycerine
– Predominately venodilation
• Arteriodilation at high doses
– Preferred agent for preload reduction
– Initial dose: 5 mcg/min IV (titrate to effect)
Vasodilators 17,19,20
• Nitroglycerine
– Adverse effects
• Hypotension
• Decrease in PAOP
• Headache
– Resistance develops quickly
Vasodilators 17,19,20
• Nesiritide
– Recombinant form of BNP
– Dose
• Initial bolus: 2 mcg/kg
• Maintenance: 0.01 mcg/kg/min
– Adverse effects
• Hypotension (dose-limiting)
– No tolerance development
13
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Case
• JD presents to the emergency department with
complaints of cough and SOB at rest. He states that
he has been unusually tired over the past few days
and has gained 10 pounds during that period. Upon
admission, his vitals are as follows:
– HR 90
– BP 185/95
– O2 sat 95%
BNP is 874 pg/mL.
Case
1. Based on JD’s signs and symptoms, which
hemodynamic subset does he most likely fit
into?
a) Subset I
b) Subset II
c) Subset III
d) Subset IV
Case
2. Which of the following would be an appropriate
initial choice of treatment for JD?
a. Furosemide PO + dobutamine IV
b. Furosemide PO + nitroglycerine IV
c. Furosemide IV bolus + dobutamine IV
Chronic Management:
Pharmacological Therapies
William Rodgers, PharmD
d. Furosemide IV bolus + nitroglycerine IV
Goals of Therapy 21
• Treat hypertension
• Treat lipid disorders
• Control metabolic syndrome
• Discourage alcohol intake and illicit drug
use
• Encourage smoking cessation
• Encourage regular exercise
Pharmacologic Classes Used in
Heart Failure 21
• Angiotensin-Converting Enzyme (ACE)
Inhibitors
• Angiotensin Receptor Blockers (ARBs)
• Beta Blockers (BB)
• Diuretics
• Digoxin
• Aldosterone Antagonists
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A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
ACE Inhibitors 18,21
• MOA: Prevent the conversion of angiotensin
I to angiotensin II, a potent vasoconstrictor
and stimulator of aldosterone secretion
• Benefits of ACE Inhibitors
– Decrease BP
– Decrease ventricular remodeling
– Reduce hospitalizations
– Decrease mortality
ACE Inhibitors 18,21
• Dosing
– Start low and titrate to target dose (next slide)
or highest dose tolerated by patient)
• Adverse Effects
– Cough, hypotension, angioedema,
hyperkalemia, worsening renal function
• Monitoring Parameters:
K+,
BP, SCr, BUN
ACE Inhibitors 21
• Recommended for all patients with current
or prior symptoms of HF and reduced left
ventricular ejection fraction (LVEF) unless
contraindicated or intolerant
• No trial has proven one ACEI superior over
another
– Recommended agents: captopril, enalapril,
lisinopril, trandolapril, perindopril, ramipril
ACEI Commonly Used for the Treatment of
Patients With Heart Failure With Low Ejection
Fraction
Drug
Initial Daily Dose(s)
Maximum Dose(s)
Captopril
6.25 mg TID
50 mg TID
Enalapril
2.5 mg BID
10 - 20 mg BID
Fosinopril
5 - 10 mg Qday
40mg Qday
Lisinopril
2.5 - 5 mg Qday
20 - 40 mg Qday
Perindopril
2 mg Qday
8-16 mg Qday
Quinapril
5 mg BID
20 mg BID
Ramipril
1.25 - 2.5mg Qday
10 mg Qday
Trandolapril
1 mg Qday
4 mg Qday
Table Adapted from Table 6 in Circulation. 2005;112;e154 - e235
ARBs 18,21
• MOA: Direct antagonists of the angiotensin II
(AT2) receptor and the angiotensin I (AT1)
receptor, which inhibits vasoconstriction,
aldosterone release, and catecholamine release
associated with angiotensin II
• Should be used as an alternative when ACE
Inhibitors are not tolerated
• Adverse Effects: Hyperkalemia, hypotension,
renal dysfunction, cough
ARBs Commonly Used for the Treatment of
Patients With Heart Failure With Low Ejection
Fraction
Drug
Initial Daily Dose(s)
Maximum Dose(s)
Candesartan
4-8 mg Qday
32 mg Qday
Losartan
25 - 50 mg Qday
50 - 100 mg Qday
Valsartan
20-40 mg BID
160 mg BID
Table Adapted from Table 6 in Circulation. 2005;112;e154 - e235
• Monitoring Parameters: K+, BP, SCr, BUN
15
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Beta Blockers 18,21
• MOA in HF: Inhibit the adverse effects of the
sympathetic nervous system on the heart by
blocking norepinephrine at the beta
adrenergic receptors
• Benefits of BB in HF
– Prevent the progression of disease
– Reverse ventricular remodeling
– Decrease hospitalizations and overall
mortality
Beta Blockers – Clinical Trials 22,23
• Cardiac Insufficiency Bisoprolol Study II (CIBIS-II)
– Bisoprolol group showed significant decrease in
all-cause mortality compared to placebo
• Metoprolol CR/XL Randomised Intervention Trial
in Congestive Heart Failure (MERIT-HF)
– Metoprolol succinate group showed significant
decrease in all-cause mortality, cardiovascularrelated mortality and total hospitalizations due to
HF.
Beta Blockers 21
• Initiation of Therapy
– BB therapy should be started as soon as LV
dysfunction is diagnosed (if patient is stable) in
addition to an ACE inhibitor
– Dosing
• Start low and titrate to target dose (see chart)
• Dose should be titrated every 2-4 weeks as
tolerated by patient
Beta Blockers 21
• Indicated for use in NYHA Class II & III HF
(benefits have been shown in nondecompensated Class IV patients)
• Drugs of Choice:
– Carvedilol
– Bisoprolol
– Metoprolol succinate
Beta Blockers – Clinical Trials 24
• Carvedilol or Metoprolol European Trial
(COMET)
– Compared carvedilol to metoprolol tartrate
– Carvedilol significantly reduced mortality
compared to metoprolol tartrate
– Limitations of this study
Beta Blockers 18
• Adverse Effects
– Bradycardia, hypotension, fatigue, fluid
retention
• Monitoring
– Heart rate, BP
• Education Points
– May take weeks to months to see benefit
– Patient may feel worse during initiation of
therapy. Why?
16
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Beta-Blockers Commonly Used for the
Treatment of Patients With Heart Failure With
Low Ejection Fraction
Diuretics 18,21
• MOA: Inhibit sodium (Na+) and/or chloride (Cl-)
reabsorption at specific sites in the renal tubule
Drug
Initial Daily Dose(s)
Maximum Dose(s)
Bisoprolol
1.25 mg Qday
10 mg Qday
– Loop diuretics: furosemide, bumetanide, torsemide,
ethacrynic acid
Carvedilol
3.125 mg BID
25 mg BID
– Thiazide diuretics: metolazone, hydrochlorothiazide,
chlorthalidone
50 mg BID > 85 kg
Metoprolol
succinate E.R.
12.5-25 mg Qday
200 mg Qday
Table Adapted from Table 6 in Circulation. 2005;112;e154 - e235
– Potassium-sparing diuretics: triamterene, amiloride,
spironolactone (aldosterone antagonist)
• May use thiazides initially, but as disease
progresses loop diuretics preferred
Diuretics 21
• Goals of therapy:
– Decrease symptoms of HF, improve quality of life,
decrease hospitalizations
• Appropriate use of diuretics is key in the
success of other drugs used for HF
– Too little diuresis: fluid retention causes diminished response to
ACE inhibitors
– Too much diuresis: volume contraction increases risk of
hypotension and renal insufficiency
• Should not be used as monotherapy
• Decrease morbidity, do NOT decrease mortality
Digoxin 18,21
• MOA: Inhibition of Na+-K+ ATPase in
myocardial cells promotes influx of Ca2+
leading to increased cardiac contractility
• Improves symptoms, quality of life, and
exercise tolerance in patients with mild to
moderate HF.
Diuretics 18,21
• Dosing
– Start low (i.e. furosemide 20-40 mg daily) and
increase dose until patient maintains a stable weight
– Titrate dose based on physical symptoms and daily
weight measurements
– Typical furosemide dose in HF: 20-160 mg/day
• Diuretic therapy should be coupled with low Na+
diet to minimize diuretic resistance
• Monitoring
– Electrolytes, blood pressure, daily weight, urine
output
Digoxin – Clinical Trial 25
• The Effect of Digoxin on Mortality and Morbidity
in Patients with Heart Failure. (The DIG trial)
– Nearly 7000 patients randomized to receive either
digoxin or placebo in addition to standard therapy
– No difference in mortality between digoxin group
and placebo
– Digoxin decreased the number of hospitalizations
due to HF by 28%
17
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Digoxin 18,21
• Role in Therapy
– Provides symptomatic relief and decreases HFrelated hospitalizations
– Adjunct for rate control in patients with
concomitant atrial fibrillation
• Initiation of Therapy
– 0.125 mg-0.25 mg once daily
– Renally cleared  dose adjust for CrCl < 50 ml/min
• Adverse Effects
Digoxin 18,21
• Monitoring
– Digoxin levels, HR, renal function, electrolytes,
symptoms of toxicity
• Digoxin Level for HF: 0.5-1.0 ng/ml
• Precautions
– Effect of digoxin is increased by hypokalemia
– Abrupt withdrawal of digoxin may cause rebound
HF exacerbation or arrhythmia
– Arrhythmias, N/V, visual disturbances
Aldosterone Antagonists 18
• Aldosterone, a mineralocorticoid, induces Na+ and
H20 retention which increases blood pressure,
while promoting the excretion of K+
• MOA: prevent aldosterone from binding to
mineralocorticoid receptors which promotes Na+
and H20 excretion and causes K+ retention
• Agents: Eplerenone and Spironolactone
Aldosterone Antagonists 26
• Effect of Spironolactone on Morbidity and
Mortality in Heart Failure (RALES Trial)
– 1663 patients with severe heart failure and LVEF
< 35% randomized to receive spironolactone or
placebo
– 30% risk reduction in mortality, 35% reduction in
hospitalizations due to HF
Aldosterone Antagonists 27
Aldosterone Antagonists 18,21
• Eplerenone Post-Acute Myocardial Infarction
Heart Failure Efficacy and Survival Study
(EPHESUS)
• Addition of aldosterone antagonists should be
considered in:
– 6642 patients 3-14 days post MI were randomized
to receive eplerenone or placebo in addition to
optimal therapy
– Eplerenone group showed 15 % decrease in all
cause mortality and 13% decrease in CV-related
death
– Patients with moderate to severe heart failure
– Patients s/p acute MI with LVEF < 40%
• Adverse Effects: Hyperkalemia, gynecomastia,
increase SCr
• Monitoring Parameters: K+, BP, SCr
18
A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
Aldosterone Antagonists Commonly Used for
the Treatment of Patients With Heart Failure
With Low Ejection Fraction
HF with Preserved Left
Ventricular Ejection Fraction 21
• Treatment Principles
Drug
Initial Daily Dose(s)
Maximum Daily Dose(s)
Spironolactone
12.5 - 25 mg Qday
25 mg Qday or BID
Eplerenone
25 mg Qday
50 mg Qday
– Control blood pressure (ACEI, ARBs)
– Control heart rate (BB, CCBs)
– Maintain fluid balance (diuretics)
Table Adapted from Table 6 in Circulation. 2005;112;e154 - e235
Case
Case
• JD is a 65 yo male who presents to his PCP for
a routine check-up . He was diagnosed with
left-sided, systolic heart failure 10 years ago.
He also has a h/o HTN, CAD, and
hyperlipidemia.
• Current Med List:
– Atenolol 50 mg daily
• What changes would you make to JD’s
medication regimen?
• What type of follow-up/monitoring would be
necessary for this regimen?
– Hydrochlorothiazide 25 mg daily
– Simvastatin 40 mg daily
References
1.
2.
Questions?
3.
4.
5.
6.
7.
Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics –
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Schwinghammer TL, Malone PM, Kolesar JM, Rotschafer JC, eds.
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McMurray JV. Systolic Heart Failure. N Engl J Med. 2010;362:228-238.
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A Comprehensive Overview of Congestive Heart Failure
November 11, 2010
Pharmacy Practice Residents Mission Hospitals 2010
References
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Vasan RS, Wilson P. Epidemiology and causes of heart failure. Colucci WS, Yeon SB,
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October 2010.
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Journal. 2010:31:1486-1493.
National Cholesterol Education Program Expert Panel. NCEP-ATP-3 Lipid Guidelines
2001.
References
16. Joint National Committee on Prevention, Detection, Evaluation and Treatment of
High Blood Pressure. JNC-7 Hypertension Guidelines 2003.
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Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic
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19. Lexi Comp Online.
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20