HEART FAILURE PHARMACY

STYLE

Molly Corder, PharmD & Faria Chaudhry, PharmD

 OBJECTIVES

Compare Compare preserved and reduced ejection fraction in heart failure

Describe Describe nonpharmacologic management of heart failure

Explain Explain pharmacologic treatment for congestive heart failure

Define Define goals of treatment for outpatient management of heart failure

Formulate a treatment plan for patients according to their history, clinical presentation
Formulate and labs.
WHY DO WE CARE?
 S TATIS TIC S

5.7 million in US  annual $30.7 billion expenditure

Most common hospitalization for adults > 65

~1 in 4 heart failure patients REHOSPITALIZED within 30 days

~ 40% survival rate one year post heart failure hospitalization AHA Journals
Cureus 2020
American College of Cardiology/ American Heart Association Task Force on
Clinical Practice Guidelines and the Heart Failure Society of America

2017 ACC/ AHA/ HFSA Focused Update of the 2013 ACCF/ AHA Guideline for
the Management of heart Failure

2013 ACCF/ AHA Guideline for the Management of Heart Failure

GUIDELINES TO USE

ACC AHA 2017

ACC AHA 2013
 DIAGNOSIS

Clinical picture Physical exam Diagnostic tests

• Dyspnea • Rales • Chest x-ray

• Orthopnea • Cool extremities • Transthoracic
• Paroxysmal • Elevated jugular echocardiography
nocturnal dyspnea venous pressure • Lab tests
• Edema
 STAGES OF HEART FAILURE:
ACC/AHA AND NYHA

Stage A Stage B Stage C Stage D

• At risk of HF • Structural heart • Structural heart • Refractory HF
but without disease but disease with requiring
structural heart without signs or prior or current specialized
disease of HF symptoms of HF symptoms interventions
symptoms heart failure

NYHA Class III:

NYHA Class I: NYHA Class II: Marked limitation of
Symptoms only Symptoms on ordinary activity with minimal
No NYHA
upon levels of exertion exertion
exertion NYHA Class III:
Symptoms on less than NYHA Class IV:
ordinary exertion Severe limitations at
rest
 HFPEF VS HFREF

Heart failure with reserved ejection fraction

EF < or = 40%

Heart failure with preserved ejection fraction

EF > or = 50%

StatPearls 2021
Circulation Research 2019
 NON-PHARMACOLOGIC MANAGEMENT

Sodium Fluid intake Alcohol

restriction restriction restriction

Weight Monitor
monitoring symptoms
PHARMACOLOGIC TREATMENT
 DRUG CLASSES USED

Beta Aldosterone
ACE/ARB Diuretics
Blocker antagonist

Hydralazine SGLT2
ARNI Digoxin
+ nitrate inhibitors
 Control Blood Pressure

Reasonable to use beta blockers

HFPEF
TREATMENT Diuretics PRN symptom relief

Aldosterone antagonist use*

• EF > or = 45
• Elevated BNP
• Admission w/in 1 year
• EGFR > 30 mL/min & Cr < 2.5
AHA/ ACC HF guidelines 2017 • Potassium <5
HFREF TREATMENT
ACC/AHA/HFSA,
Management of Heart
Failure, JACC, 2017
 LOOP DIURETICS

No long-term mortality
benefit
Worsening kidney function
Electrolyte imbalance

Optimize volume status

Relieve symptoms
Reduce risk of worsening HF
 LOOP DIURETIC AGENTS

Bumetanide Torsemide Furosemide

PO 1 mg 20 mg 80 mg

IV 1 mg 20 mg 40 mg

Split up dose Metolazone, chlorothiazide,

Diuretic resistance? chlorthalidone,
hydrochlorothiazide
 ACE INHIBITORS/ ARB’S

Inhibition of the
Reduces Reduces
renin angiotensin
morbidity mortality
system

Blood pressure
Renal Protective
control

Micromedex
Lexicomp
 ACE/ ARB COUNSELING POINTS

• Adverse effects:
ACE inhibitors ARBs

Cough (bradykinin pathway) Less Cough

Hyperkalemia Hyperkalemia

Teratogenicity Teratogenicity

Acute renal failure Acute renal failure

Angioedema Angioedema

Micromedex
Lexicomp
 ARNI’S

Inhibition of the renin angiotensin system with ARNI

(neprilysin inhibitor) (level B evidence)

Sacubitril/ Valsartan

HFrEF: reduce morbidity and mortality (PARADIGM HF)

HFpEF: Conflicting data (PARAGON HF)

Micromedex
Lexicomp
 ARNI COUNSELING POINTS

36 HOUR WASH CONSIDER

OUT PERIOD ADVERSE EFFECTS
OF ARB’S
 Reduce cardiovascular
mortality and sudden death

BETA Reduce hospitalization

BLOCKERS

May reduce all-cause

mortality
 BETA BLOCKERS

Mechanism of action: Blockade of cardiac beta-1 adrenergic receptors. Slows

conduction and prolongation in the refractory period of the AV note

Medication Target Dose Adverse Effects Trial

Bisoprolol 10 mg daily CIBIS II study: 34%
all-cause mortality
Monitor for reduction
hypotension, blood
Carvedilol 25 to 50 mg twice daily glucose, weight gain, COPERNICUS: 35%
mortality reduction

Metoprolol succinate 200 mg daily MERIT-HF trial

extended release 34% reduction in all-
cause mortality
 BIDIL

Isosorbide dinitrate & hydralazine

Improve survival (African Americans w/ NYHA class 3 & 4)

Adjunct treatment with standard of care

Kamath, Curr Treat Options Cardiovasc Med. 2005

 Reduce all-cause mortality

Reduce hospitalizations in
ALDOSTERONE patients with left ventricular
ANTAGONISTS dysfunction and heart failure

Use in symptomatic heart failure

with reduce ejection fraction
<35%
 ALDOSTERONE ANTAGONISTS

Mechanism of action: Competitive binding of receptors at the aldosterone-dependent sodium-

potassium exchange site in the distal convoluted renal tubule.

Medication Dose Notes Adverse Effects

Eplerenone Before starting
Spironolactone Initial 12.5 mg to - Serum creatinine Gynecomastia,
25 mg with a <2.5 mg/dL in hyperkalemia,
maximum of 50 mg men and <2 hepatotoxicity
daily mg/dL in women
- Serum potassium
<5 mEq/L
Jardiance:
Empagliflozin
SGLT2
Farxiga: Dapagliflozin INHIBITORS

Invokana:
Canagliflozin
 SGLT2 INHIBITOR MECHANISM

Decreases renal tubular No insulin release Decreases blood

glucose reabsorption pressure & weight

Micromedex
Lexicomp
 S G LT2 I N H I B I TO R M ECH A N I S M
I N H EA RT FA I L U RE

Heart  Improved cardiac remodeling &

decreased oxidative stress

Kidney Increased diuresis

Vasculature  decreased inflammation,

decreased BP

Body  Increase weight loss

ALL PROVIDE BENEFITS IN HEART

FAILURE

JACC Basic Transl Sci 2020

 Improved CV outcomes & all cause mortality

Meta analysis decreased all cause mortality,

CV mortality, HF hospitalizations, & renal
complications
SGLT2
INHIBITORS DAPA HF  HFrEF regardless +/- DM 
lower risk of death

HFpEF  Emerging data (EMPEROR –

Preserved) (reduced risk of CV death & HF
hospitalization)

AHA SGLT2 inhibitors in heart failure 2019

ESC Heart fail. 2021
N Engl J Med 2019
 Evidence for positive inotropy

Vasodilation

DIGOXIN Diuresis

Slowing of rapid ventricular rate

Decreases hospitalizations, clinical

decompensation, possible mortality

AHA 2004
WHAT IS THE GOAL TROUGH FOR
DIGOXIN USE IN HEART FAILURE?

0.5 – 0.9 ng/ mL

MEDICATIONS THAT EXACERBATE
HEART FAILURE

Pioglitazone
Anti-arrhythmic
Calcium channel blockers, cyclophosphamide
Metformin
Antidepressants, antimalarials, anthracyclines
Nsaids

AHA, 2016, Drugs

that may cause or
exacerbate HF
 MEDICATIONS THAT EXACERBATE
HEART FAILURE CONTINUED

• DPP4 Inhibitors (saxagliptin, sitagliptin)

• Itraconazole
• Anthracyclines (doxorubicin, daunorubicin)
• TNF alpha inhibitors (infliximab, adalimumab, etanercept)
• Antimalarials (chloroquine, hydroxychloroquine)
 CONCLUSIONS

Implement Implement lifestyle modifications

Monitor Monitor for symptoms of exacerbation

Start Start GDMT with max tolerated doses

Improve Improve symptoms to enhance quality of life

Prevent Prevent progression of heart failure

Classify Classify type of heart failure to help guide therapy

QUESTIONS
 PATIENT CASES

Split into groups of 4

Work up patient case

Pick 1-2 people to present the case

FAMILY FEUD
 REFERENCES

• Ellison DH, Felker GM. Diuretic Treatment in Heart Failure. N Engl J Med 2017; 377:1964.
• Heart Failure Society of America, Lidenfeld J, Albert NM, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. K Card Fail 2010l 16:e1.
• Trends in 30- and 90-Day Readmission Rates for Heart Failure | Circulation: Heart Failure (ahajournals.org)
• Nair R, Lak H, Hasan S, Gunasekaran D, Babar A, Gopalakrishna KV. Reducing All-cause 30-day Hospital Readmissions for Patients Presenting with Acute Heart Failure Exacerbations: A
Quality Improvement Initiative. Cureus. 2020;12(3):e7420. Published 2020 Mar 25. doi:10.7759/cureus.7420
• Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of the 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; 135:e137.
• Hajouli S, Ludhwani D. Heart Failure And Ejection Fraction. [Updated 2021 Jan 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK553115/
• Pfeffer M, Shah A, Borlaug B. Heart failure with preserved ejection fraction in perspective. Originally published23 May 2019https://doi.org/10.1161/CIRCRESAHA.119.313572Circulation
Research. 2019;124:1598–1617
• Yancy C, Jessup M, Bozkurt B. 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. J Am Coll Cardiol. 2017 Aug, 70 (6) 776–803. Accessed
• Kamath SA, Yancy CW. Treatment of the African-American patient with congestive heart failure. Curr Treat Options Cardiovasc Med. 2005 Aug;7(4):307-15. doi: 10.1007/s11936-005-
0041-z. PMID: 16004861.
• Hsia DS, Grove O, Cefalu WT. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. 2017;24(1):73-79.
doi:10.1097/MED.0000000000000311
• PubMed Central, Figure 1: JACC Basic Transl Sci. 2020 Jun; 5(6): 632–644. Published online 2020 Jun 22. doi: 10.1016/j.jacbts.2020.02.004 (nih.gov)
• Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors (nih.gov)
• Anker SD, Butler J, Filippatos G, Shahzeb Khan M, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Gomez-Mesa JE, Janssens S,
Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Seronde MF, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D,
Zhang J, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Preserved Trial Committees and Investigators. Baseline characteristics of patients
with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial. Eur J Heart Fail. 2020 Dec;22(12):2383-2392. doi: 10.1002/ejhf.2064. PMID: 33251670.
• Breakthrough results for Jardiance® (empagliflozin) confirm EMPEROR-Preserved as first and only successful trial for heart failure with preserved ejection fraction | Eli Lilly and Company
• Butler J, Usman MS, Khan MS, et al. Efficacy and safety of SGLT2 inhibitors in heart failure: systematic review and meta-analysis [published correction appears in ESC Heart Fail. 2021
Jun;8(3):2362]. ESC Heart Fail. 2020;7(6):3298-3309. doi:10.1002/ehf2.13169
• McMurray J, Solomon S, Inzucchi S. et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. November 21, 2019
N Engl J Med 2019; 381:1995-2008 DOI: 10.1056/NEJMoa1911303
• Lam C, Chandramouli C, Ahooja V, Verma S. SGLT2 inhibitors in Heart failure: current management, unmet needs and therapeutic prospects. Originally published 12 Oct 2019
https://doi.org/10.1161/JAHA.119.013389Journal of the American Heart Association. 2019;8:e013389
• https://doi.org/10.1161/01.CIR.0000132477.32438.03