−This Clinical Resource gives subscribers

additional insight related to the Recommendations published in−

July 2017 ~ Resource #330703

Heart Failure Treatment at a Glance

The chart below delineates the role of medications and other interventions for chronic systolic heart failure (heart failure with reduced ejection
fraction [HFrEF]). For more information on dosing and monitoring, see our chart, Target Doses of Medications for Systolic Heart Failure. For an
educational handout you can customize for your patient, get our patient handout, Heart Failure Meds and More. Our toolbox, Improving Heart
Failure Care, provides practical tips and resources to help improve care in your heart failure patients and prevent readmissions.
Abbreviations: ACEI=angiotensin-converting enzyme inhibitor, ARB=angiotensin receptor blocker, ARNI=angiotensin receptor-neprilysin inhibitor, BNP=B-type
natriuretic peptide, HF=heart failure, LVEF=left ventricular ejection fraction, MI=myocardial infarction, NT-proBNP=N-terminal pro-BNP, SBP = systolic blood
pressure
**Information in chart may differ from product labeling. Recommendations from Canadian HF guidelines are included if differ from U.S.**
Drug, Drug Class, or Use for…
Intervention
First-Line
ACEI • Patients with LVEF 40% or less (<40%, Canada), with symptoms or prior symptoms, unless contraindicated, to reduce
morbidity and mortality.1,2
• Asymptomatic patients with LVEF 35% or less (Canada).2
Comments:
• Use with a beta-blocker.1

Beta-Blocker • Stable patients with LVEF 40% or less, with symptoms or prior symptoms, as soon as HF is diagnosed, unless
contraindicated, to reduce morbidity and mortality.1
Comments:
• Use with an ACEI.3
• Can start beta-blocker before ACEI is optimized.1
• Use an evidence-based beta-blocker (carvedilol, bisoprolol, metoprolol succinate [U.S. only]).1

Diuretics • Patients with fluid retention or a history of fluid retention, to improve symptoms and exercise tolerance, and to manage
beta-blocker associated fluid retention.1
Comments:
• Loops preferred, but thiazides can be considered for patients with hypertension and mild fluid retention.1
Continued… • Adjust dose to attain and maintain target (dry) weight.1
More. . .
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 (Clinical Resource #330703: Page 2 of 5)

Drug, Drug Class, or Use for…

Intervention
Diuretics, Furosemide: initial 20 to 40 mg once or twice daily, max total daily dose 600 mg
continued Bumetanide: initial 0.5 to 1 mg once or twice daily, max total daily dose 10 mg
Torsemide: initial 10 to 20 mg once daily, max total daily dose 200 mg

Education to facilitate • Patients with symptoms or prior symptoms, to prevent hospitalization and reduce length of stay.1
HF self-care
Sodium restriction • All patients, to reduce symptoms and improve diuretic efficacy.1

Exercise (regular • Symptomatic but clinically stable patients who are able, to improve function and quality of life, reduce mortality, and
physical activity or reduce hospitalizations.1
cardiac rehab)
Second-Line
ARB • Patients who are intolerant to ACEI due to cough or angioedema, and in whom an ACEI or ARNI is inappropriate.3
• Patients already taking an ARB for another indication (e.g., hypertension), as an ACEI alternative.3
• Patients with Class II to IV HF and LVEF 40% or less at high risk of HF events despite optimized ACEI plus beta-
blocker (i.e., as an add-on to ACEI plus beta-blocker) (Canada).2
• Patients who cannot take a beta-blocker, as an add-on to an ACEI (Canada).2
Comment:
• Do not combine with ACEI plus aldosterone antagonist.1

Aldosterone • Patients with Class II to IV HF and LVEF 35% or less (Canada: Class IIIB or IV HF and LVEF <30%), unless
Antagonist contraindicated, to reduce morbidity and mortality.1,2 (Patients with Class II HF should have a history of
(eplerenone or cardiovascular hospitalization or elevated BNP.)1
spironolactone) • Patients over 55 years of age with mild to moderate HF despite standard treatment and a LVEF 30% or less (or 35% or
less if QRS duration over 130 ms) and cardiovascular hospitalization within the previous six months or elevated BNP
or NT-proBNP levels (Canada).2
• Post-MI patients with LVEF 40% or less (30% or less, Canada) with symptoms or a history of diabetes, unless
contraindicated, to reduce morbidity and mortality.1,2
Comments:
• Do not start if baseline creatinine is over 2.5 mg/dL (221 umol/L) in men or over 2 mg/dL (176.8 umol/L) in women, or
eGFR is 30 mL/min/1.73 m2 or lower, or potassium is 5 mEq (mmol)/L or higher.1
• Used as an add-on to ACEI (or ARB) plus beta-blocker.1

More. . .
Copyright © 2017 by Therapeutic Research Center
3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
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 (Clinical Resource #330703: Page 3 of 5)

Drug, Drug Class, or Use for…

Intervention
Third-Line
ARNI • Patients with chronic symptomatic Class II or III heart failure tolerating an adequate ACEI or ARB dose, as a substitute
(sacubitril/valsartan for ACEI or ARB.3
[Entresto]) • Canada: for patients with class II to IV symptoms despite treatment with ACEI or ARB, beta-blocker, and aldosterone
antagonist at maximally-tolerated dose, as a substitute for ACEI or ARB.6
Comments:
• Do not use with an ACEI or within 36 hours of the last dose of an ACEI, or another ARB.3,4
• Do not start if patient has SBP <100 mmHg, symptomatic hypotension, hyperkalemia, or a history of ACEI/ARB
angioedema.3,4
• Prevents CV death or heart failure hospitalization in 1 in 21 patients treated for two years vs an ACEI, but also causes
symptomatic hypotension in 1 in 21 patients [Evidence level A; high-quality RCT].4

Hydralazine and • Patients of African ancestry with class III or IV HF and LVEF 40% or lower who are symptomatic despite optimized
Isosorbide Dinitrate ACEI or ARB plus beta-blocker (i.e., as an add-on to ACEI [or ARB] plus beta-blocker), to reduce morbidity and
mortality, unless contraindicated.1
• Patients who cannot take an ACEI or ARB (i.e., in place of ACEI or ARB with beta-blocker).1

Ivabradine • Patients with symptomatic Class II or III stable chronic heart failure with LVEF of 35% or lower, in sinus rhythm with
(Corlanor [U.S.], resting heart rate of 70 beats per minute or greater, in addition to guideline-directed therapy, including a beta-blocker at
Lancora [Canada]) a maximally-tolerated dose, or who cannot take a beta-blocker.3,5
• Canada: add-on for patients with class II to IV symptoms (stable Class II to III with LVEF 35% or less, per labeling)
despite maximally-tolerated doses of ACEI or ARB, beta-blocker, and aldosterone antagonist, who are in sinus rhythm
with resting heart rate of 70 beats (77 beats, per labeling) per minute or greater.6,8
Comments:
• Reduces heart failure hospitalization in one in 25 patients vs placebo when added to standard therapy [Evidence level
A; high-quality RCT].7
• Causes bradycardia in one in 13 patients and atrial fibrillation in one in 100 patients vs placebo.5,7

More. . .
Copyright © 2017 by Therapeutic Research Center
3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
PharmacistsLetter.com ~ PrescribersLetter.com ~ PharmacyTechniciansLetter.com ~ NursesLetter.com
 (Clinical Resource #330703: Page 4 of 5)

Drug, Drug Class, or Use for…

Intervention
Fourth-Line
Digoxin • Patients with LVEF 40% or less, with persistent symptoms despite optimized treatments above, to decrease HF
hospitalization, unless contraindicated.1 Used as add-on to the optimized regimen.1
• Patients with atrial fibrillation and poor rate control despite beta-blocker.1
Comments:
• No loading dose needed for HF.1
• Consider target levels of 0.5 to 0.9 ng/mL (0.6 to 1.2 nmol/L).1
• Consider starting with 0.125 mg every-other-day in patients with renal insufficiency, low lean body mass, or age over
70 years.1 Doses over 0.25 mg per day rarely needed.1

Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical
judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national
organizations. Information and internet links in this article were current as of the date of publication.

More. . .
Copyright © 2017 by Therapeutic Research Center
3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
PharmacistsLetter.com ~ PrescribersLetter.com ~ PharmacyTechniciansLetter.com ~ NursesLetter.com
 (Clinical Resource #330703: Page 5 of 5)

Levels of Evidence 2. McKelvie RS, Moe GW, Ezekowitz JA, et al. The
In accordance with the trend towards Evidence-Based 2012 Canadian Cardiovascular Society heart failure
management guidelines update: focus on acute and
Medicine, we are citing the LEVEL OF EVIDENCE chronic heart failure. Can J Cardiol 2013;29:168-81.
for the statements we publish. 3. Yancy CW, Jessup M, Bozkurt B, et al. 2017
Level Definition ACC/AHA/HFSA focused update of the 2013
A High-quality randomized controlled trial (RCT) ACCF/AHA guideline for the management of heart
High-quality meta-analysis (quantitative failure: a report of the American College of
systematic review) Cardiology/American Heart Association Task Force
B Nonrandomized clinical trial on Clinical Practice Guidelines and the Heart Failure
Nonquantitative systematic review Society of America. Circulation 2017 Apr 28 [Epub
Lower quality RCT ahead of print]. doi:
Clinical cohort study 10.1161/CIR.0000000000000509.
Case-control study 4. McMurray JJ, Packer M, Desai AS, et al.
Historical control Angiotensin-neprilysin inhibition versus enalapril in
Epidemiologic study heart failure. N Engl J Med 2014;371:993-1004.
C Consensus 5. Product information for Corlanor. Amgen, Inc.
Expert opinion Thousand Oaks, CA 91320. April 2015.
D Anecdotal evidence 6. Howlett JG, Chan M, Ezekowitz JA, et al. The
In vitro or animal study Canadian Cardiovascular Society heart failure
Adapted from Siwek J, et al. How to write an evidence-based clinical companion: bridging guidelines to your practice.
review article. Am Fam Physician 2002;65:251-8. Can J Cardiol 2016;32:296-310.
7. Swedberg K, Komajda M, Bohm M, et al. Ivabradine
and outcomes in chronic heart failure (SHIFT): a
Project Leader in preparation of this clinical randomised placebo-controlled study. Lancet
resource (330703): Melanie Cupp, Pharm.D., 2010;376:875-85.
BCPS 8. Product monograph for Lancora. Laval, QC H7V
4A7. December 2016.
References
1. Yancy CW, Jessup M, Bozkurt B, et al. 2013
ACCF/AHA guideline for the management of heart
failure: a report of the American College of
Cardiology Foundation/American Heart Association
Task Force on Practice Guidelines. Circulation
2013;128:e240-e327.

Cite this document as follows: Clinical Resource, Heart Failure Treatment at a Glance. Pharmacist’s
Letter/Prescriber’s Letter. July 2017.

Evidence and Recommendations You Can Trust…

3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249
Copyright  2017 by Therapeutic Research Center

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