Introduction

Heart failure (HF) is a progressive disease state resulting from disorders of the pericardium, myocardium, endocardium, heart valves or from certain metabolic diseases. Heart failure is the preferred term over congestive heart failure, since not every patient presents with fluid overload. Patients with heart failure will often have symptoms of left ventricular (LV) myocardium dysfunction. HF patients can have a wide range of LV functions leading to various ejection fraction (EF).

Diagnosis Classification

The two widely accepted classifications of HF are the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) stages of HF and the New York Heart Association (NYHA) functional classifications. The ACCF/AHA stages focus on the development and progression of HF. The NYHA functional classification focuses on the symptoms of the HF and how it reflects on daily activity and exercise tolerance.

Treatment Algorithm

Treatment approaches vary depending on the patient's clinical presentation of HF. The following table and flowchart demonstrate the treatment algorithm based on the ACCF/AHA stage and NYHA functional classification.

Treatment Options

This section provides a list of common medications used in each class of the HF treatment. It is intended to provide an overview of the treatment options, prices of medications per dose, common adverse drug reactions (ADR) and black box warnings (BBW) of each medication classes.

Table 1.

Demographic characteristics of the respondents

Demographic characteristics of the respondents
Demographic characteristics of the respondents

Treatment Recommendation

This section provides the author's recommendation on how to select a drug in each class. The recommendations provided are based on national guidelines, clinical trials and national association recommendations as provided in references #516.

ACE Inhibitor (Step 1 for ACCF/AHA Stage A, B, C)(5,6)

  • ACE inhibitors are preferred over ARB for the reduction in all-cause mortality and cardiovascular (CV) death in patients with either left ventricular dysfunction due to acute myocardial infarction or chronic heart failure.(7)

  • CrCl≥10 mL/minute

    • ○ Start enalapril 2.5 mg titrate slowly with one- to two-week intervals to 40 mg QD for the greatest increase in EF, stroke volume (SV) and decrease mean arterial pressure (MAP).

    • ○ If side effects (cough, Gastrointestinal discomfort, renal function deterioration) intolerable

      • ▪ Change to ramipril 1.25 mg titrating up to 10 mg QD for the benefit of lowing all-cause mortality.

    • ○ If hepatic impairment, start lisinopril 2.5–5 mg QD titrate up by 10 mg every one to two weeks until 40 mg QD

  • Risk of angioedema increases with the concurrent use of neprilysin inhibitors

  • ACE inhibitor contraindicated with sacubitril

  • Avoid ACE inhibitor therapy in non-dialysis patients with creatinine clearance (CrCl)<20 mL/minute

  • ARBs (Step 1 for ACCF/AHA Stage A, B, C)(8)

  • Candesartan and valsartan preferred over other ARBs based on their efficacy to suppress aldosterone.(9)

  • Start candesartan 4–8 mg QD and titrate up to 32 mg QD or valsartan 20 to 40 mg BID and titrate up to 160 mg BID.(10,11)

Table 2.

Definition of HFrEF and HFpEF

Definition of HFrEF and HFpEF
Definition of HFrEF and HFpEF
Table 3.

ACCF/AHA Stages of HF and NYHA Functional Classifications

ACCF/AHA Stages of HF and NYHA Functional Classifications
ACCF/AHA Stages of HF and NYHA Functional Classifications
Figure 1.

Stage C and NYHA Class I–IV Medication Treatment

Figure 1.

Stage C and NYHA Class I–IV Medication Treatment

Figure 2.

Stage A, B and D Treatment

Figure 2.

Stage A, B and D Treatment

Table 4.

Cost of Treatment Per Dose

Cost of Treatment Per Dose
Cost of Treatment Per Dose
Table 4.

Cost of Treatment Per Dose

Cost of Treatment Per Dose
Cost of Treatment Per Dose
Cost of Treatment Per Dose
Cost of Treatment Per Dose
Table 4.

Cost of Treatment Per Dose

Cost of Treatment Per Dose
Cost of Treatment Per Dose
Cost of Treatment Per Dose
Cost of Treatment Per Dose
Table 4.

Cost of Treatment Per Dose

Cost of Treatment Per Dose
Cost of Treatment Per Dose
Cost of Treatment Per Dose
Cost of Treatment Per Dose

Beta Blockers (Step 2 for ACCF/AHA Stage B, C)(1214)

  • For all patients with reduced ejection fraction.

  • Start with carvedilol 3.125 mg BID titrate up every two to four weeks as tolerated up to 25 mg BID or 50 mg BID if patient (pt)>85 kg for a greater improvement in LVEF comparing to metoprolol succinate and a greater effect on overall mortality comparing to bisoprolol.(1517)

  • If 25 mg carvedilol not tolerable then use one of the following:

    • ○ Bisoprolol 1.25 mg QD titrate up every two or more weeks as tolerated up to 10 mg QD.(18)

    • ○ Metoprolol succinate 12.5 to 25 mg QD every two or more weeks as tolerated up to 200 mg QD.(19)

    • ○ Switching among the three recommended beta blockers not recommended.

    • ○ Watch for signs of resistant edema for possible dose adjustment or discontinuation.

  • Contraindication

    • ○ 2nd or 3rd degree atrioventricular heart block without pacemaker

    • ○ Heart rate<50 bpm without pacemaker

    • ○ Asthma

ARNI (Step 2 for ACCF/AHA Stage C, HFrEF NYHA Class II–lll)(20)

Used for its benefit of reducing left atrial size, reverse left atrial remodeling and improve in NYHA class.(21)

  • If patient with adequate BP (Systolic Blood Pressure>100 mmHg) and eGFR≥30 mL/min on moderate to high dose ACEI or ARB,

    • ○ Start Sacubitril/Valsartan (Entresto) at 49 mg/51 mg BID, titrate up by doubling dose every two to four weeks until 97 mg/103 mg BID.

  • If patient with adequate BP on low dose ACEI or ARB or no ACEI or ARB,

    • ○ Start Sacubitril/Valsartan (Entresto) at 24 mg/26 mg BID, titrate up by doubling dose every two to four weeks until 97 mg/103 mg BID.

  • Contraindication

    • ○ Angioedema

Aldosterone antagonists (Step 3 for ACCF/AHA Stage C)

  • Eplerone is preferred over spironolactone due to the endocrine related adverse effects.

Diuretic (Step 3 for ACCF/AHA Stage C)(22)

  • Start with furosemide 20 mg QD, titrate up to BID. Use the lowest possible dose to achieve goal.

  • BID dosing to avoid post-diuretic rebound sodium retention.

  • If loop diuretic resistance, add Hydrochlorothiazide 25–100 mg to achieve sequential blockade.

Statins (primary/secondary prevention for cardiovascular disease for ACCF/AHA Stage A, B, C, NYHA class II to IV, EF<35%)(8,23)

  • Initiate atorvastatin 10–20 mg (moderate statin therapy) for patients:

    • ○ Low density lipoprotein cholesterol (LDLC)<190 mg/dL and 10-year cardiovascular disease (CVD) risk of 10 percent or greater

  • Initiate atorvastatin 80 mg (high intensity statin therapy) for patients:

    • ○ LDL-C≥190 mg/dL without familiar hypercholesterolemia.

  • Do not initiate statin therapy with patients with LDL-C<190 mg/dL and 10-year cardiovascular disease (CVD) risk of less than 5 percent.

  • LDL fewer than 30 leads to higher cardiovascular risk.

Abbreviations

     
  • ACCF:

    American College of Cardiology Foundation

  •  
  • ACEI:

    angiotensin-converting enzyme inhibitors

  •  
  • ADR:

    adverse drug reactions

  •  
  • AF:

    atrial fibrillation

  •  
  • AHA:

    American Heart Association

  •  
  • ARB:

    angiotensin-receptor blockers

  •  
  • ARNI:

    angiotensin receptor-Neprilysin inhibitors

  •  
  • ASCVD:

    atherosclerotic cardiovascular diseases

  •  
  • BBW:

    black box warnings

  •  
  • BID:

    twice daily

  •  
  • BP:

    blood pressure

  •  
  • BPM:

    beats per minute

  •  
  • C/I:

    contraindicated

  •  
  • CrCl:

    creatinine clearance

  •  
  • CVD:

    cardiovascular disease

  •  
  • DM:

    diabetes mellitus

  •  
  • EF:

    ejection fraction

  •  
  • eGFR:

    estimated Glomerular filtration rate

  •  
  • GDMT:

    guideline-directed medical treatment

  •  
  • HF:

    heart failure

  •  
  • HFpEF:

    heart failure with preserved ejection fraction

  •  
  • HFrEF:

    heart failure with reduced ejection fraction

  •  
  • HTN:

    hypertension

  •  
  • LDL-C:

    low density lipoprotein cholesterol

  •  
  • LV:

    left ventricular

  •  
  • LVAD:

    left ventricular assist device

  •  
  • LVEF:

    left ventricular ejection fraction

  •  
  • MAP:

    mean arterial pressure

  •  
  • MI:

    myocardial infarction

  •  
  • N/A:

    not applicable

  •  
  • NYHA:

    New York Heart Association

  •  
  • Pt:

    patient

  •  
  • QD:

    once daily

  •  
  • SrCr:

    serum creatinine level

  •  
  • SV:

    stroke volume

  •  
  • TID:

    three times daily

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About the Author

Stephanie Lee is a 2022 PharmD candidate at the Western University of Health Sciences in Pomona, CA. She has no conflicts of interest to report.

Craig S. Stern, RPh, PharmD, MBA, FASCP, FASHP, FICA, FLMI, FAMCP, FCPhA, CSP is the president of Pro Pharma Pharmaceutical Consultants in Chatsworth, CA, a professor pharmacy at the University of Southern California, University of California, San Francisco and Western University of Health Sciences, and an adjunct professor and preceptor at the University of the Pacific. He is a fellow of the Academy of Managed Care Pharmacy, the American Society of Consultant Pharmacists and the American Society of Health-System Pharmacists. Dr. Stern has no conflicts of interest to report.