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Chapter 10 Outpatient Management of Stable Heart Failure with Reduced Ejection Fraction
Chapter 11 Exercise and Rehabilitation in Heart Failure
Chapter 12 The Patient with Ischemic Heart Failure
Chapter 13 The Non-Ischemic HEART FAILURE Patient
Chapter 14 Valvular Heart Disease and Heart Failure
Chapter 15 The Management of Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)
Chapter 16 Heart Failure with Recovered Ejection Fraction (HFrecEF) and Heart Failure with Midrange Ejection Fraction (HFmrEF)
Chapter 17 The Advanced HEART FAILURE Patient
Chapter 18 Palliative Care and Advanced Directives in Heart Failure
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Chapter 10
OUTPATIENT MANAGEMENT OF STABLE HEART FAILURE WITH REDUCED EJECTION FRACTION
Leah Reid, Jonathan Murrow, Kent Nilsson, and Catherine Marti
DOI: 10.1201/9780429244544-13
Introduction
Although therapies for HF with preserved ejection fraction (HFpEF) are lacking, there are many therapies available to patients with HF with reduced ejection fraction (HFrEF), regardless of symptomatology.1 Careful consideration should be taken at every encounter to evaluate not only volume status but also to optimize guideline-directed medical therapy as well as device therapy. In this chapter, we outline the current therapy available for outpatient management of HFrEF (Table 10.1).
TABLE 10.1: Starting and Target Doses of Select Established and Novel Therapies for Heart Failure | | Starting Dose (mg) | Target Dose (mg) |
| Beta-Blockers |
| Bisoprolol | 1.25 daily | 10 daily |
| Carvedilol | 3.125 b.i.d. | 25 b.i.d. for weight <85 kg and 50 b.i.d. for weight ≥85 kg |
| Metoprolol succinate | 12.5–25 daily | 200 daily |
| Angiotensin Receptor Neprilysin Inhibitors |
| Sacubitril/valsartan | 24/26–49/51 b.i.d. | 97/103 b.i.d. |
| Angiotensin-Converting Enzyme Inhibitors |
| Captopril | 6.25 t.i.d. | 50 t.i.d. |
| Enalapril | 2.5 b.i.d. | 10–20 b.i.d. |
| Lisinopril | 2.5–5.0 daily | 20–40 daily |
| Ramipril | 1.25 daily | 10 daily |
| Angiotensin II Receptor Blockers |
| Candesartan | 4–8 daily | 32 daily |
| Losartan | 25–50 daily | 150 daily |
| Valsartan | 40 b.i.d. | 160 b.i.d. |
| Aldosterone Antagonists |
| Eplerenone | 25 daily | 50 daily |
| Spironolactone | 12.5–25 daily | 25–50 daily |
| Sodium-Glucose Cotransporter-2 Inhibitors |
| Dapagliflozin | 10 daily | 10 daily |
| Empagliflozin | 10 daily | 10 daily |
| Vasodilators |
| Hydralazine | 25 t.i.d. | 75 t.i.d. |
| Isosorbide dinitrate | 20 t.i.d. | 40 t.i.d. |
| Fixed-dose combination isosorbide dinitrate/hydralazine | 20/37.5 (1 tab) t.i.d. | 2 tabs t.i.d. |
| Ivabradine |
| Ivabradine | 2.5–5 b.i.d. | Titrate to heart rate 50–60 beats/min. Maximum dose 7.5 b.i.d. |
| Notes: Isosorbide mononitrate is not recommended by current guidelines, which consider either the fixed-dose combination or the separate combination of isosorbide dinitrate and hydralazine as appropriate guideline-directed therapies for heart failure. |
| Abbreviations: b.i.d. = bis in die (twice daily); t.i.d. = ter in die (three times daily). |
| Source: Reproduced with permission from: Maddox et al., J Am Coll Cardiol 2021;77:772–810. |
Beta-Blockers
Maladaptive activation of the sympathetic nervous system in HFrEF can lead to worsening congestion, malperfusion, and arrhythmias.2 Blockade of β-adrenergic receptors has proven in multiple clinical trials to reduce morbidity and mortality—specifically with metoprolol succinate and bisoprolol, which selectively block β-1-receptors, and with carvedilol, which selectively blocks α-1, β-1 and β-2 receptors.3
In the landmark Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), patients with HFrEF (ejection fraction [EF] ≤35%) and New York Heart Association (NYHA) class II–IV symptoms had a 34% relative risk reduction in all-cause mortality with bisoprolol therapy vs placebo.4 The Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) and carvedilol trials likewise demonstrated reduced risk of death or HF hospitalization (Figure 10.1).5–7 To reduce morbidity and mortality, the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Heart Failure Guidelines thus recommend using either bisoprolol, carvedilol, or sustained-release metoprolol succinate for all patients with current or prior symptoms of HFrEF unless contraindicated (class I, level of evidence [LOE]: A). Importantly, the benefit of β blockers is dose dependent, with lower achieved heart rates associated with improved outcomes, albeit this effect is mostly relevant to patients in sinus rhythm and not among those with atrial fibrillation.8 A network meta-analysis of 21 trials found a mortality benefit of β blockers vs p...
