Heart Failure Guidelines: Introduction to the New Agents

G. Blair Sarbacker, PharmD, BCACP; Alyson G. Wilder, PharmD, BCPS

US Pharmacist. 2018;43(2):22-26.

Updated Guidelines

In May 2016, the American College of Cardiology, the AHA, and the Heart Failure Society of America published a focused update on new pharmacologic therapy for HF. The update was spurred by recent evidence regarding HF, and the new drugs sacubitril/valsartan and ivabradine were included in the update. Because these two new agents have evidence only for stage C HFrEF, this was the only section of the guidelines to be updated; recommendations for the other stages of HF are unchanged. Accordingly, practitioners are using both the 2013 ACCF/AHA guideline for the management of HF and the new update.^[5] To aid the reader's understanding of the management of stage C HFrEF, the treatment algorithm from the 2013 ACCF/AHA guideline for the management of HF has been updated here to include the 2016 recommendations (Figure 1).^[5,8]

(Enlarge Image)

Figure 1.

Updated Treatment Algorithm Based on ACCF/AHA Guideline for Management of Heart Failure
ACEI: ACE inhibitor; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor; BB: beta-blocker; GDEM: guideline-directed evaluation and management; HRrEF: heart failure with reduced ejection fraction; K+: potassium; LVEF: left ventricular ejection fraction; max: maximum; NYHA: New York Heart Association; SCr: serum creatinine. Source: References 5, 8.

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Table 1. Staging of Heart Failure
ACCF/AHA Classification	NYHA Classification
A—At high risk for HF, but without structural heart disease or symptoms of HF	None
B—Structural heart disease, but without signs or symptoms of HF	I—No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF
C—Structural heart disease with prior or current symptoms of HF	I—No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF II—Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF
	III—Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF
	IV—Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest
D—Refractory HF requiring specialized interventions	IV—Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest

ACCF: American College of Cardiology Foundation; AHA: American Heart Association; HF: heart failure; NYHA: New York Heart Association.
Source: Reference 5.

Table 2. Summary of Novel Heart Failure Agents
Agent	Pharmacokinetics/Pharmacodynamics	Dosing	Adverse Events
Sacubitril/valsartan (Entresto)	Steady state: 3 days Protein binding: 94%-97% Renal elimination: Sacubitril (primarily as LBQ657): 52%-68% Valsartan: ~13% Fecal elimination: Sacubitril (primarily as LBQ657): 37%-48% Valsartan: 86% T_1/2: Sacubitril: 1.4 h LBQ657: 11.5 h Valsartan: 9.9 h	49/51 mg bid; double after 2 wk to target maintenance dosage of 97/103 mg bid	≥5%: hypotension, hyperkalemia, cough, dizziness, renal failure
Ivabradine (Corlanor)	Protein binding: ~70% Metabolism: hepatic (3A4) Renal elimination: 4% as unchanged drug T_1/2: Distribution: 2 h Effective: 6 h	5 mg bid or 2.5 mg bid in patients with history of conduction defects or bradycardia. Assess resting heart rate 2 wk after initiation and adjust dose to achieve resting heart rate of 50–60 bpm. Maximum dosage of 7.5 mg bid	≥5%: atrial fibrillation, bradycardia, hypertension

T_1/2: half-life.
Source: References 9, 10.

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