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Heart Failure Guideline Review and Update

Natalie Beiter, PharmDPGY1 Pharmacy ResidentAvera McKennan Hospital

Disclosure

• I have had no financial relationship over the past 12 months with any commercial sponsor with a vested interest in this presentation.

Pharmacist Objectives

1. Identify the symptoms associated with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)

2. Given a patient with HFrEF or HFpEF, explain the current guideline-based treatment options for mortality benefit and symptom relief

Pharmacy Technician Objectives

1. Select medications approved for use in patients with heart failure and identify their recommended dosages

2. Identify non-pharmacologic treatment options for patients with heart failure

What is Heart Failure?

• Chronic, progressive disease of the heart

• Any structural or functional impairment of ventricular filling or ejection of blood

• Approximately 6.5 million American adults currently live with heart failure

Cardinal Symptoms of Heart Failure

• Dyspnea• Fatigue, leading to exercise intolerance

• Fluid retention• Pulmonary and/or• Splanchnic congestion and/or• Peripheral edema

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Heart Failure Classifications

Preserved Ejection Fraction (HFpEF)• EF ≥50%

• Diastolic Heart Failure

• Symptoms:• Pulmonary Edema

Reduced Ejection Fraction (HFrEF)• EF ≤40%

• Systolic Heart Failure

• Symptoms:• Peripheral Edema

Functional Classification of Heart Failure

ACCF/AHA Stages• Development and progression

of disease

• Stages A through DA. At risk, no structural disease or

symptomsB. Structural disease without

signs or symptomsC. Structural disease with prior or

current symptomsD. Refractory disease requiring

specialized interventions

NYHA• Exercise capacity and

symptomatic status of disease

• Classes I-IVI. No limitation of physical

activityII. Slight limitation of physical

activityIII. Marked limitation of physical

activityIV. Unable to carry out any

physical activity without symptoms, symptoms at rest

Treatment Recommendations

AHA Heart Failure Guidelines 2013

Non-pharmacological Treatment Options

• Sodium restriction• <2 gram/day

• Fluid restriction• 1.5-2 L/day• Especially in Stage D

• Activity• 150 minutes of moderate activity/week

• Smoking Cessation

• Vaccinations• Influenza• Pneumococccal

Stage A

Goals:• Heart healthy lifestyle• Prevent vascular, coronary

disease and left ventricular structural abnormalities

• Control co-morbid disease states:• Hypertension• Lipid disorders• Obesity• Diabetes Mellitus

Avoid tobacco and cardiotoxic agents

Drug therapy• Vascular disease, diabetes

mellitus, hypertension• ACEI or ARB

• Statins

Stage B

Goals:• Prevent heart failure

symptoms• Prevent further cardiac

remodeling

Drug Therapy• All patients with HFrEF:

• Initiate ACEI or ARB• Initiate beta blocker

• Cardiac history (MI or ACS)• Initiate statin

• If the patient has structural cardiac abnormalities:• Control blood pressure

Avoid:• Non-dihydropyridine calcium

channel blockers

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Stage C Goals of Therapy

HFpEFGoals:• Control symptoms• Improve quality of life• Prevent hospitalization• Prevent mortality

Strategies:• Identification of comorbidities

HFrEFGoals:• Control symptoms• Patient education• Prevent hospitalization• Prevent mortality

Stage C Drug Therapy Recommendations

HFpEF• Diuresis for symptom relief

• Follow guideline driven indications for comorbidities• Hypertension• Atrial Fibrillation• Coronary Artery Disease• Diabetes Mellitus

HFrEF• Drugs for routine use:

• Diuretics• ACEI or ARB• Beta-blocker• Aldosterone Antagonists

• Drugs for use in selected patients:• Hydralazine/isosorbide dinitrate• ACEI and ARB• Digoxin

Loop Diuretics

Agents:• Furosemide (Lasix)• Bumetanide (Bumex)• Torsemide (Demadex)• Ethacrynic acid (Edecrin)

Use in heart failure:• Decrease fluid volume• Used only for symptom control

• No morbidity or mortality benefit• Use lowest effective dose

Adverse effects:• Decreased potassium,

magnesium, calcium, chloride• Increased uric acid levels• Photosensitivity

Monitoring• Renal function• Electrolytes• Fluid status• Blood pressure

ACE Inhibitors/Angiotensin Receptor Blockers

ACE Inhibitors• Agents:

• Lisinopril• 20-40 mg once daily

• Enalapril• 10-20 mg BID

• Ramipril• 5 mg BID or 10 mg daily

• Captopril• 50-100 mg TID (max 450

mg/day)

ARBs• Agents:

• Valsartan• 160 mg BID

• Losartan• 150 mg daily

• Candesartan• 32 mg once daily

ACE Inhibitors/Angiotensin Receptor Blockers

• Reduction in morbidity and mortality• Decrease in preload and

afterload due to their effects on the renin-angiotensin aldosterone system

• Adverse Effects:• Angioedema• Cough (ACEI only)• Hyperkalemia• Hypotension

• Monitoring:• Blood pressure• Potassium• Renal function

Beta-Blockers

• Agents• Metoprolol Succinate (Toprol XL)

• Goal dose: 200 mg daily• Bisoprolol (Zebeta)

• Goal dose: 10 mg daily• Carvedilol (Coreg)

• Goal dose: 25 mg BID

• Proven reduction in morbidity and mortality• Help improve cardiac function

• Adverse Effects:• Bradycardia• Hypotension• Fatigue• Dizziness

• Monitoring:• Heart Rate• Blood Pressure

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Aldosterone Antagonists

• Agents:• Spironolactone

• 25 mg once or twice daily• Eplerenone

• 50 mg daily

• Morbidity and mortality reduction• Increase serum and water

excretion

• Adverse Effects:• Hyperkalemia• Elevated SCr• Dizziness• Gynecomastia

• Spironolactone only

• Monitoring:• Potassium• SCr, BUN, fluid status

Hydralazine/Isosorbide Dinitrate

• Guideline recommendations:• Alternative for patients who cannot tolerate and ACEI or ARB• In addition to an ACEI or ARB in African-American patients with HFrEF

• NYHA class III-IV HFrEF

• Morbidity and mortality reduction

• Dosing:• Fixed combination dose: Isosorbide dinitrate 40 mg/hydralazine 75 mg TID• Separate dosing: Isosorbide dinitrate 40 mg TID with hydralazine 100 mg TID

Digoxin

• Used for symptom management• No morbidity or mortality benefit

• Loading dose not required in heart failure• Goal level: 0.5-0.9 ng/mL

• Side effects:• Bradycardia, dizziness, nausea, vomiting, diarrhea, vision changes

• Monitoring:• Heart rate, blood pressure, electrolytes, renal function

Stage D

Goals:

• Control symptoms

• Improve quality of life

• Reduce hospital readmissions

• Establish patient’s end-of-life goals

Options:

• Water restriction• 1.5-2 L/day

• Advanced care measures

• Heart transplant

• Chronic inotropes

• Experimental surgery or drugs

Guideline Updates

2017 ACC/AHA/HFSA Focused Update

Losartan/sacubatril (Entresto)

• Mechanism: ARNI (Angiotensin Receptor Neprilysin Inhibitor)• Angiotensin receptor blockade antagonizes vasoconstriction and aldosterone

release• Neprilysin inhibition prevents the breakdown of BNP, thus increasing natriuretic

peptides

• Dosing: • Dosage form: Oral tablet

• (Sacubatril-valsartan): 24 mg-26 mg; 49 mg-51 mg; 97 mg-103 mg• Dosing is based on previous ACEI/ARB dose

• Ensure 36 hour washout period if previously on an ACEI or ARB• Titrate to maintenance dose of 97 mg-103 mg twice daily

• Adverse Effects:• Hypotension, hyperkalemia, dizziness, angioedema• BBW: Fetal injury or death; discontinue in pregnancy

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Losartan/sacubatril (Entresto)

• Clinical evidence:• PARADIGM-HF

• Entresto vs. moderate dose enalapril• Results: Losartan/sacubatril significantly decreased mortality and

symptoms/hospitalizations

• Place in therapy:• “The clinical strategy of the renin-angiotensin system with ACE inhibitors

OR ARBs OR ARNI in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients is recommended for patients with chronic HFrEF to reduce morbidity and mortality.”

• “In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate and ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality”

Ivabradine (Corlanor)

• Mechanism: • Selective inhibition of the If current in the SA node leading to reduced heart

rate

• Dosing:• Initial: 5 mg po BID• Dose adjust based on heart rate with goal heart rate between 50-60 bpm• Maximum dose of 7.5 mg po BID

• Adverse Effects:• Atrial fibrillation, bradyarrhythmias, luminous phenomena

Ivabradine (Corlanor)

• Place in therapy:• “Ivabradine can be beneficial to reduce HF hospitalization for patients with

symptomatic (NYHA class II-III) stable chronic HFrEF who are receiving guideline-directed management and therapy, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.”

Pharmacist Post-Test Questions

1. Which of the following is/are symptom(s) of HFrEF?

a. Peripheral Edema

b. Weakness and fatigue

c. Dyspnea

d. All of the above

Pharmacist Post-Test Questions

2. Which of the following drugs has been shown to reduce mortality in patients with HFrEF?

a. Furosemide

b. Ivabradine

c. Metoprolol succinate

d. Digoxin

Pharmacy Technician Post-Test Questions

1. What is the brand name of the combination product losartan/sacubatril that has been approved for use in heart failure?

a. Vasotec

b. Hyzaar

c. Entresto

d. Cozaar

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Pharmacy Technician Post-Test Questions

2. Which of the following non-pharmacologic, lifestyle modifications can a patient make per guideline recommendations?

a. Smoking cessation

b. Sodium restriction

c. Fluid restriction

d. All of the above

Questions?

References

• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the american college of cardiology/american heart association gaskforce on clinical practice guidelines and the heart failure society of america. Circulation 2017; CIR.0000000000000509.

• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary, a report of the american college of cardiology foundations/american heart association task force on practice guidelines. JACC 2013; 62 (16): 1495-1539.