CME
No longer failing to treat heart failure:
A guideline update review
Jonathan Parch, MPAP, PA-C; Chloe Powell, MPAS, PA-C
Downloaded from http://journals.lww.com/jaapa by BhDMf5ePHKbH4TTImqenVErHeFes2idEPSsV01R8a9Jl+BC0JsVj39enlr+iYs+y on 06/10/2019
ABSTRACT
Heart failure is a leading cause of hospital admissions and
death in the United States and worldwide. In 2016, the
American Heart Association, the American College of Car-
diology, and the Heart Failure Society of America released a
joint focused guideline update for the management of patients
with Stage C heart failure with reduced ejection fraction.
An additional update released in 2017 reinforces the 2016
update’s strong recommendation for substituting angiotensin-
converting enzyme inhibitors or angiotensin receptor blockers
with an angiotensin receptor-neprilysin inhibitor to reduce
morbidity and mortality in selected patients. The 2017 and
2016 updates also support adding a sinoatrial node modula-
tor to further reduce heart rates in patients already maxi-
mized on beta-blocker therapy. These innovative therapies
can significantly improve patients’ quality of life and reduce
the healthcare costs associated with managing heart failure.
Keywords: heart failure, ivabradine, angiotensin receptor-
neprilysin inhibitor, ARNI, angiotensin-converting enzyme
inhibitor, angiotensin receptor blocker
Jonathan Parch practices cardiothoracic surgery at the Smidt Heart Insti-
tute at Cedars-Sinai Medical Center in Los Angeles, Calif. Chloe Powell
is a clinical instructor of family medicine in the Primary Care Physician
Assistant Program at the University of Southern California’s Keck School
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2019 American Academy of Physician Assistants
©ISTOCK/ERAXION
H
eart failure affects more than 23 million people
worldwide.1 In the United States, more than 5.8
million patients have heart failure and more than
550,000 patients are diagnosed each year.1 Heart failure
accounts for close to 1 million hospitalizations a year with
25% of those patients readmitted to a hospital within 30
days.1 Heart failure consists of a wide spectrum of abnor-
malities, ranging from heart failure with preserved ejection
fraction to heart failure with reduced ejection fraction
(defined as a left ventricular [LV] ejection fraction of 40%
or less).2
Guidelines published in 2013 by the American College
of Cardiology Foundation/American Heart Association
(ACC/AHA) helped to expand the use of evidence-based
pharmocotherapies, reducing the rate of sudden death in
patients with heart failure by 44%.3 In 2016, the AHA/
ACC/Heart Failure Society of America (HFSA) released a
joint focused guideline update for heart failure manage-
ment specifically related to two new medications recom-
mended to further reduce hospitalizations and increase life
of Medicine in Alhambra, Calif. The authors have disclosed no potential
conflicts of interest, financial or otherwise.
DOI:10.1097/01.JAA.0000550282.19722.93
Copyright © 2019 American Academy of Physician Assistants
www.JAAPA.com 11
CME
Learning objectives
Describe the changes made to the 2013 ACCF/AHA heart
failure guidelines with the 2016 and 2017 updates.
Explain the benefits of non-pharmacologic therapy for
heart failure.
Compare and contrast the use of ACE inhibitors or ARBs
with an angiotensin receptor neprilysin inhibitor and the
use of beta-blockers with ivabradine.
Key points
Heart failure is a leading cause of hospital admissions
and death.
A guideline update recommends replacing an ACE
inhibitor or ARB with an ARNI for patients with stage C
heart failure with reduced ejection fraction.
These patients also may be helped by ivabradine, which
lowers heart rate without reducing BP.
expectancy in a subset of patients with heart failure.4 A
2017 focused guideline update reinforced these recommen-
dations.5 This article focuses on the 2016 and 2017 guide-
line changes related to the use of two new medications for
the treatment of heart failure with reduced ejection fraction.
PATHOPHYSIOLOGY
Heart failure is defined as the heart’s inability to supply
sufficient blood to meet the body’s metabolic requirements.2
Cardiac injury or dysfunction that precipitates cardiac
remodeling can result in heart failure.2 Common causes of
injury or dysfunction include ischemic heart disease, chronic
hypertension, and valvular disorders.2 Other contributing
factors include congenital heart defects, diabetes, anemia,
and alcohol abuse.2 Early compensatory mechanisms become
active when decreased cardiac output stimulates barorecep-
tors and the sympathetic nervous system.6 As a result of
low cardiac output, decreased renal perfusion activates the
renin-angiotensin-aldosterone system, which attempts to
restore cardiac output and tissue perfusion. During times
of volume overload in the ventricles, the myocardium secretes
natriuretic peptides.2 These neurohormonal responses
eventually lead to vasoconstriction and fluid retention,
causing an increase in pressure that the heart must work
against, further reducing cardiac output. Therapies that
block activation of these maladaptive responses can improve
myocardial function and slow down disease progression.6
SIGNS AND SYMPTOMS
The primary symptoms of acute decompensated heart
failure are exertional dyspnea, orthopnea, paroxysmal
nocturnal dyspnea, and fatigue.2 Common clinical signs
of fluid retention include bibasilar crackles, pleural effu-
sions, tachycardia, S3 gallop, jugular venous distension,
12 www.JAAPA.com
Copyright © 2019 American Academy of Physician Assistants
ascites, hepatomegaly, and pitting edema. Patients with
chronic heart failure who have been medically optimized
may present in acute decompensated heart failure without
signs or symptoms of fluid overload.2 Many patients
treated for an acute decompensation of heart failure will
experience a recurrence of fluid accumulation, promoting
another cycle of decompensation and requiring repeat
hospitalizations.
DIAGNOSTIC STRATEGIES
Heart failure is a complex clinical syndrome and the
diagnosis is made clinically through a careful history and
physical examination. Both the ACC/AHA stages of heart
failure and the New York Heart Association (NYHA)
functional classification provide useful and complementary
information about the presence and severity of heart
failure.2 The ACC/AHA stages emphasize the disease
development and progression and can be used to describe
patients and populations; the NYHA classes focus on
exercise capacity and the symptomatic status of the dis-
ease.2 These stages and functional classifications guide
clinical judgment in treating patients with or at risk for
heart failure.
The 2013 guideline recommended that the initial evalu-
ation of patients presenting with signs and symptoms of
acute decompensation of previously undiagnosed heart
failure include a complete blood cell count, urinalysis,
serum electrolytes (including calcium and magnesium),
blood urea nitrogen, serum creatinine, glucose, fasting lipid
profile, liver function tests, and thyroid-stimulating hor-
mone.2 Identifying and managing comorbidities can sig-
nificantly improve outcomes for patients with heart failure.
The 2013 guideline also recommended obtaining an
anterior-posterior chest radiograph in patients with heart
failure or at risk for it, to look for cardiomegaly, pulmonary
congestion, and other possible causes of their symptoms.2
However, considering the low sensitivity and specificity of
the chest radiograph, it should not be the sole determinant
of the diagnosis of heart failure.2
Obtain biomarker levels The 2013 guideline recommended
two biomarkers—brain natriuretic peptide (BNP) and
N-terminal pro-B-type natriuretic peptide (NT-proBNP)—
to help diagnose heart failure.2 The 2017 update reempha-
sizes the usefulness of these biomarkers for diagnosing and
evaluating acute decompensated and chronic heart failure
and for differentiating pulmonary from cardiac causes in
patients with shortness of breath.5 According to the 2017
update, an accurate prognosis of acute decompensated
heart failure is best made by obtaining baseline levels of
natriuretic peptide biomarkers when the patient is admit-
ted to the hospital.5 Levels of these biomarkers are measured
in the blood and are elevated during heart failure exacer-
bations, decreasing with treatment. If these values do not
fall after aggressive heart failure therapy, the patient is at
significant risk of death or hospitalization.2
Volume 32 • Number 1 • January 2019

New data suggest that natriuretic peptide biomarker
screening and early intervention by a cardiovascular spe-
cialist to optimize direct medical therapy may prevent LV
dysfunction or new-onset heart failure.5 However, consis-
tent evidence for improvement in mortality and cardiovas-
cular outcomes is lacking. The 2017 update does not
provide recommendations related to natriuretic peptide-
guided therapy or serial measurements of BNP or NT-
proBNP levels for the purpose of reducing hospitalizations
or deaths.5
Cardiac troponin I and T, cardiac biomarkers that indi-
cate cardiac muscle damage in patients with acute coronary
syndrome, also are found at abnormal levels in patients
with heart failure.7 The 2016 guideline recommended
measuring these biomarkers in patients presenting with
acute decompensation of heart failure.4 Elevated troponin
levels in patients with acute decompensated or chronic
ambulatory heart failure are associated with a worse
clinical outcome and increased mortality; decreasing levels
over time indicate a better prognosis.7
Perform a noninvasive cardiac evaluation The guideline
recommends asking patients about any history of palpita-
tions or dysrhythmias and obtaining a 12-lead electrocar-
diogram.2 A 24-hour ambulatory electrocardiography device
or event recorder may be useful to evaluate rate control
and the type of dysrhythmia.2 The 2013 guideline recom-
mends two-dimensional echocardiography as the most
useful diagnostic test for evaluating patients with or at risk
for heart failure. Transthoracic or transesophageal echo-
cardiogram in patients with suspected heart failure can help
identify disease and lead to appropriate medical care.2
Perform an invasive cardiac evaluation Right-heart cath-
eterization, also known as pulmonary artery catheterization,
is a more invasive technique used to evaluate and manage
advanced heart failure. The 2013 guideline recommended
right-heart catheterization for patients with a clinically
indeterminate volume status, those in respiratory distress,
or those who do not respond to initial therapy for heart
failure.2 A catheter is advanced from the femoral or inter-
nal jugular vein through the right side of the heart and into
the pulmonary artery to assess intracardiac filling pressures,
quantify LV ejection fraction, and monitor the patient’s
hemodynamic response to medical therapies. Routine use
of right-heart catheterization is not recommended in nor-
motensive patients with acute decompensated heart failure.2
HISTORICAL PERSPECTIVE
Treatment of heart failure has evolved over the past 20
years, with the focus shifting from controlling symptoms
to reversing the cardiac dysfunction and remodeling that
occurs. Terminology also has changed with the improved
understanding of the disease process. The condition was
once commonly referred to as congestive heart failure but
the preferred term today is heart failure. This term encom-
passes all patients, including those with a primary filling
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2019 American Academy of Physician Assistants
No longer failing to treat heart failure: A guideline update review
defect (diastolic heart failure), who may not present with
symptoms of pulmonary congestion and have a preserved,
or normal, ejection fraction. Patients with a normal ejec-
tion fraction account for almost 50% of patients with heart
failure.8 Describing heart failure as left-sided, right-sided,
systolic, diastolic, acute, or chronic remains useful in
understanding its pathophysiology and current status.
NONPHARMACOLOGIC MANAGEMENT
The nonpharmacologic management of patients with heart
failure consists of a multifaceted approach. According to
the 2013 guideline, patient education, sodium intake
restriction, exercise training, and cardiac rehabilitation all
can be used to improve patient outcomes.2 The 2017 update
recommends continuous positive airway pressure (CPAP)
for patients with heart failure and obstructive sleep apnea
(OSA), and recommends against adaptive servo-ventilation
for patients with heart failure and central sleep apnea.5
Appropriate use of these interventions yields many benefits,
including a reduction in symptoms, an improved quality
of life, reduced hospitalizations, and reduced mortality.
Patient education Patients with heart failure must receive
specific education about self-care.2 Emphasize the impor-
tance of taking medications as prescribed, remaining
physically active, and taking their weight each morning.
Teach patients to identify signs of fluid retention and how
to adjust their diuretic therapy or contributing dietary
factors as needed. Establish a diuretic strategy that patients
can implement as needed and encourage patients to
communicate with their healthcare providers about any
changes in their volume status and daily diuretic dosage.
Advise patients to restrict alcohol consumption and
avoid tobacco; provide support for cessation if necessary.
Patients with heart failure should avoid nonsteroidal
anti-inflammatories or use them with caution.2
Remind patients to speak with their healthcare provider
before starting any new medications. Patient education
and adherence can help reduce healthcare costs, hospital-
izations, and patient mortality.2
Restricting sodium intake Patients with symptomatic
heart failure should restrict their sodium intake to reduce
congestive symptoms. Giving precise recommendations
about daily sodium intake is challenging because heart
failure and comorbidities have variable effects on sodium
homeostasis.2 To minimize the development of hyperten-
sion, LV hypertrophy, and cardiovascular disease, the AHA
recommends a maximum sodium intake of 1.5 g per day
for most patients with AHA stage A or B heart failure.2
Data are insufficient to endorse any specific level of sodium
intake for patients with stage C or D heart failure. Clini-
cians are encouraged to consider restricting sodium intake
to less than 3 g per day for patients with stage C or D heart
failure, to reduce heart failure exacerbation, as the typical
sodium intake is more than 4 g per day in the general
population.2
www.JAAPA.com 13
CME
Exercise training and cardiac rehabilitation Exercise is
safe and effective for patients with heart failure who can
participate. Cardiac rehabilitation can be useful in clinically
stable patients with heart failure. Regular physical activity
and cardiac rehabilitation have numerous benefits, includ-
ing improvement of functional capacity, improved quality
of life, and reduced mortality.2
OSA vs. central sleep apnea Because patient response
to therapy for OSA and central sleep apnea differs, distin-
guishing these two conditions in patients with heart failure
is crucial. Nocturnal CPAP can improve sleep quality and
reduce daytime sleepiness in patients with OSA.9 However,
CPAP has shown no benefit in cardiovascular events for
patients with heart failure and OSA.9
The 2017 update recommends against using adaptive
servo-ventilation in patients with heart failure and central
sleep apnea.5 A recent study found that these patients had
higher mortality when this type of ventilation was used.10
A decision to refer a patient for a sleep study should be
based on clinical judgment.2
PHARMACOLOGIC MANAGEMENT
The 2013 guideline outlined optimal medications, as defined
by the term guideline-directed medical therapy, for patients
with stage C heart failure with reduced ejection fraction.
This therapy consists of angiotensin-converting enzyme
(ACE) inhibitors (or angiotensin receptor blockers [ARBs]
for patients who cannot tolerate ACE inhibitors), and one
of three beta-blockers (bisoprolol, carvedilol, or metopro-
lol succinate).2
Additional therapy for certain patients may include loop
diuretics, aldosterone receptor antagonists, anticoagulants,
digoxin, and combination hydralazine/isosorbide dinitrate.2
UPDATED GUIDELINES
The 2017 update discusses new pharmacologic therapies
for patients with stage C heart failure with reduced ejection
fraction: an angiotensin receptor-neprilysin inhibitor
(ARNI) and a sinoatrial node modulator. The update was
proceeded by two important studies that have led to a
global change in pharmacologic treatment guidelines for
heart failure. Implementing these therapies has been shown
to reduce heart failure–related hospitalizations and reduce
cardiovascular and all-cause mortality.11
ARNI In the Prospective Comparison of Angiotensin
Receptor Neprilysin Inhibitor with ACE inhibitor to
Determine Impact on Global Mortality and Morbidity in
Heart Failure (paradigm-hf) trial, the ARNI (a combina-
tion of sacubitril and valsartan) demonstrated its superior-
ity in reducing mortality and morbidity risk compared
with the gold standard, the ACE inhibitor enalapril.12
Patients taking the ARNI had a 20% reduction in cardio-
vascular mortality and reduced hospitalizations for heart
failure over 27 months compared with patients receiving
a target dose of 10 mg enalapril twice daily.12 Using data
14 www.JAAPA.com
Copyright © 2019 American Academy of Physician Assistants
from the paradigm-hf trial, researchers estimated that
patients treated with an ARNI instead of an ACE inhibitor
or ARB would gain an additional 1 to 2 years of life and
have a significant reduction in hospitalizations.13
Neprilysin is a neutral endopeptidase that is elevated in
patients with heart failure.11 Primarily found in the kidney,
it can exist in numerous tissues, including the vascular
smooth muscle, lung, and cardiac myocytes. Neprilysin
breaks down and inactivates many peptides that have vaso-
dilatory and other favorable cardiovascular effects, such as
the atrial and B-type natriuretic peptides, bradykinin, and
adrenomedullin.14 However, neprilysin also has favorable
cardiovascular effects: it can inactivate systemic vasocon-
strictors such as endothelin I and angiotensin II.14 Because
sacubitril for neprilysin inhibition alone would have mixed
effects in managing patients with heart failure with reduced
ejection fraction, it has been combined with the ARB val-
sartan to minimize the undesirable effects of angiotensin II.
One of the first studies to demonstrate the potential
benefit of neprilysin inhibition for patients with heart
failure was the IMPRESS randomized trial, which compared
vasopeptidase inhibitor, omapatrilat, and lisinopril on
exercise tolerance and morbidity in patients with heart
failure. Omapatrilat is a dual inhibitor of ACE and nepri-
lysin.15 In the IMPRESS trial, omapatrilat showed a greater
reduction in risk of death or hospitalization for heart
failure than enalapril alone; however, the effect was based
on a small number of clinical events observed in patients
who were treated for 6 months.16
Subsequently, the Omapatrilat Versus Enalapril Random-
ized Trial of Utility in Reducing Events (overture) study
was performed to definitively compare the effects of omapa-
trilat and enalapril on outcomes in patients with heart
failure.15 The study determined that omapatrilat reduced
morbidity and mortality of patients with moderate to severe
heart failure compared with enalapril alone.15 The overture
trial was ended because of an associated increased risk of
angioedema.15 This study confirmed the potential value of
neprilysin inhibition in addition to RAAS modulation for
patients with heart failure, and ultimately resulted in the
development of the ARNI.
Patients with chronic heart failure (NYHA classes II
through IV), an elevated plasma BNP or NT-proBNP level,
and an LV ejection fraction less than 40% should be con-
sidered for treatment with an ARNI rather than an ACE
inhibitor or ARB.17
The results from the paradigm-hf trial were so promis-
ing that the 2017 update recommends replacing ACE
inhibitors and ARBs with the ARNI for patients with stage
C heart failure with reduced ejection fraction in order to
further reduce morbidity and mortality.5 To minimize the
risk of angioedema caused by overlapping an ACE inhibi-
tor and the ARNI during substitution, withhold the ACE
inhibitor for at least 36 hours before starting the ARNI.5
ARNI therapy is contraindicated in patients with a history
Volume 32 • Number 1 • January 2019

of angioedema.5 Dual treatment with an ACE inhibitor (or
ARB) and ARNI also is contraindicated.17 Patients already
on an ACE inhibitor or ARB may be started on the ARNI
at an oral dose of 49/51 mg twice daily; the dose should be
doubled in 2 to 4 weeks to a target dose of 97/103 mg twice
daily.18 BNP levels will increase in patients on an ARNI and
decompensation should be measured with NT-proBNP.19
Sinoatrial modulation Ivabradine is a new therapeutic
agent that selectively inhibits the If current in the sinoatrial
node, reducing heart rate without lowering BP. The 2017
update supports using ivabradine to further reduce heart
rates in patients with stage C heart failure with an LV
ejection fraction of 35% or less.5 These patients should
already be receiving optimal medical therapy, including a
beta-blocker at the maximum tolerated dose and should
be in normal sinus rhythm with a heart rate of 70 beats/
minute or greater at rest.5 Ivabradine is available in three
dosages (2.5, 5, and 7.5 mg), is given twice a day, and is
titrated until the patient’s heart rate is between 50 and 60
beats/minute.20
The Systolic Heart Failure Treatment with the If Inhibi-
tor Ivabradine Trial (SHIFT) investigated the effect of
isolated heart rate reduction on outcomes in patients with
heart failure. In SHIFT, the maximum studied dose of 7.5
mg of ivabradine twice daily significantly reduced hospi-
talizations for heart failure exacerbation by 18% when
compared with placebo.20 Of the 6,558 patients involved
in the study, only about 25% were receiving optimal doses
of beta-blocker therapy.20 Given the mortality benefits of
beta-blocker therapy, the 2017 update recommends max-
imizing beta-blockade, as tolerated, before assessing the
patient’s resting heart rate and considering ivabradine
therapy.5
CONCLUSION
The 2017 ACC/AHA/HFSA guideline update recommends
that to further reduce patient morbidity and mortality,
clinicians replace an ACE inhibitor or ARB with the ARNI
for patients with stage C heart failure with reduced ejection
fraction who already are receiving adequate doses of an
ACE inhibitor or ARB.5 Ivabradine can be effective as a
supplemental medication for patients already maximized
on beta-blockers who need additional heart rate reduction.5
Optimizing medical therapy, supporting behavior modifi-
cation, treating comorbidities, and closely monitoring
patients with heart failure will slow down disease progres-
sion and reduce the healthcare costs associated with this
complex syndrome. JAAPA
Earn Category I CME Credit by reading both CME articles in this
issue, reviewing the post-test, then taking the online test at http://cme.
aapa.org. Successful completion is defined as a cumulative score of at
least 70% correct. This material has been reviewed and is approved
for 1 hour of clinical Category I (Preapproved) CME credit by the
AAPA. The term of approval is for 1 year from the publication date of
January 2019.
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2019 American Academy of Physician Assistants
No longer failing to treat heart failure: A guideline update review
REFERENCES
1. Roger VL. Epidemiology of heart failure. Circ Res. 2013;113(6):
646-659.
2. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline
for the management of heart failure: a report of the American Col-
lege of Cardiology Foundation/American Heart Association Task
Force on practice guidelines. Circulation. 2013;128(16):e240-e327.
3. Shen L, Jhund PS, Petrie MC, et al. Declining risk of sudden
death in heart failure. N Engl J Med. 2017;377(1):41-51.
4. Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA
focused update on new pharmacological therapy for heart
failure: an update of the 2013 ACCF/AHA guideline for the
management of heart failure: a report of the American College
of Cardiology/American Heart Association Task Force on
Clinical Practice Guidelines and the Heart Failure Society of
America. Circulation. 2016;134(13):e282-e293.
5. Yancy CW, Jessup M, Bozkurt B, 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 Task Force on
Clinical Practice Guidelines and the Heart Failure Society of
America. Circulation. 2017;136(6):e137-e161.
6. Jackson G, Gibbs CR, Davies MK, Lip GY. ABC of heart failure.
Pathophysiology. BMJ. 2000;320(7228):167-170.
7. Peacock WF 4th, De Marco T, Fonarow GC, et al. Cardiac
troponin and outcome in acute heart failure. N Engl J Med.
2008;358(20):2117-2126.
8. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence
and outcome of heart failure with preserved ejection fraction.
N Engl J Med. 2006;355(3):251-259.
9. McEvoy RD, Antic NA, Heeley E, et al. CPAP for prevention of
cardiovascular events in obstructive sleep apnea. N Engl J Med.
2016;375(10):919-931.
10. Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive servo-
ventilation for central sleep apnea in systolic heart failure. N Engl
J Med. 2015;373(12):1095-1105.
11. Bayés-Genís A, Barallat J, Galán A, et al. Soluble neprilysin is
predictive of cardiovascular death and heart failure hospitalization
in heart failure patients. J Am Coll Cardiol. 2015;65(7):657-665.
12. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin
inhibition versus enalapril in heart failure. N Engl J Med. 2014;
371(11):993-1004.
13. Claggett B, Packer M, McMurray JJ, et al. Estimating the long-term
treatment benefits of sacubitril-valsartan. N Engl J Med. 2015;
373(23):2289-2290.
14. Hsiao R, Greenberg B. Neprilysin inhibition as a PARADIGM shift
in heart failure therapy. Curr Heart Fail Rep. 2016;13(4):172-180.
15. Packer M, Califf RM, Konstam MA, et al. Comparison of
omapatrilat and enalapril in patients with chronic heart failure:
the Omapatrilat Versus Enalapril Randomized Trial of Utility in
Reducing Events (OVERTURE). Circulation. 2002;106(8):920-926.
16. Rouleau JL, Pfeffer MA, Stewart DJ, et al. Comparison of
vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise
tolerance and morbidity in patients with heart failure: IMPRESS
randomised trial. Lancet. 2000;356(9230):615-620.
17. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines
for the diagnosis and treatment of acute and chronic heart failure:
The Task Force for the diagnosis and treatment of acute and
chronic heart failure of the European Society of Cardiology (ESC).
Developed with the special contribution of the Heart Failure Asso-
ciation (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891-975.
18. Cada DJ, Baker DE, Leonard J. Sacubitril/valsartan. Hosp Pharm.
2015;50(11):1025-1036.
19. Mair J, Lindahl B, Giannitsis E, et al. Will sacubitril-valsartan diminish
the clinical utility of B-type natriuretic peptide testing in acute cardiac
care? Eur Heart J Acute Cardiovasc Care. 2017;6(4):321-328.
20. Swedberg K, Komajda M, Böhm M, et al. Ivabradine and
outcomes in chronic heart failure (SHIFT): a randomised
placebo-controlled study. Lancet. 2010;376(9744):875-885.
www.JAAPA.com 15