contemporary approaches to the management of chronic heart … · 2017. 10. 11. · contemporary...

Contemporary Approaches to the Management of Chronic Heart Failure: An

Overview

Presented as a Live Webinar

Wednesday, October 5, 2016

12:00 p.m. – 1:00 p.m. ET

www.ashpadvantage.com/go/chf

Planned by ASHP Advantage and supported by an educational grant from Novartis Pharmaceuticals Corporation

Contemporary Approaches to the Management of Chronic Heart Failure: An Overview

Activity Overview This series of educational activities begins with an online activity reviewing basic concepts in heart failure, pharmacologic strategies, and new and emerging therapies. The series continues with a clinical case workshop using patient scenarios to illustrate how complications, dosing, patient parameters, and other factors affect therapy in heart failure. The cases will follow patients from the beginning of the disease and beyond, when complications arise and more than one approach to therapy might be considered.

Learning Objectives At the conclusion of this Knowledge-based educational activity, participants should be able to

• Review the pathophysiology and demographics of chronic heart failure in the United States.• Describe current strategies for effective pharmacologic and non-pharmacologic management of

patients with chronic heart failure.• Compare the pharmacology and mechanism of action for medications used in managing chronic

heart failure, including the role of new agents in therapy.

Continuing Education Accreditation ASHP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity provides 1.0 hour (0.1 CEU – no partial credit) of continuing pharmacy education credit (ACPE activity #0204-0000-16-463-L01-P).

Participants will process CPE credit online at http://elearning.ashp.org/my-activities. CPE credit will be reported directly to CPE Monitor. Per ACPE, CPE credit must be claimed no later than 60 days from the date of the live activity or completion of a home study activity.

Webinar Information Visit www.ashpadvantage.com/go/chf/webinar1 to find

• Webinar registration link• Group viewing information and technical requirements• CPE webinar processing information

Copyright © 2016, American Society of Health‐System Pharmacists, Inc. All rights reserved.

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http://elearning.ashp.org/my-activities

http://www.ashpadvantage.com/go/chf/webinar1


Faculty Robert J. DiDomenico, Pharm.D., BCPS-AQ Cardiology, FCCP Clinical Professor College of Pharmacy University of Illinois at Chicago Cardiovascular Clinical Pharmacist University of Illinois Hospital Chicago, Illinois

Robert J. DiDomenico, Pharm.D., FCCP, is Clinical Professor in the Department of Pharmacy Practice, and Faculty of the Center for Pharmacoepidemiology and Pharmacoeconomic Research at the University of Illinois at Chicago (UIC). He is also Cardiovascular Clinical Pharmacist at the University of Illinois Hospital & Health Sciences System with a practice site in inpatient cardiology. Dr. DiDomenico serves as Residency Program Director for the UIC PGY2 Cardiology Pharmacy residency. Since 2008, he has chaired the Educational Policy Committee at the UIC College of Pharmacy.

Dr. DiDomenico received his Pharm.D. and completed three years of post-doctoral training (Pharmacy Practice Residency, Cardiovascular Pharmacotherapy Fellowship) at UIC.

Dr. DiDomenico has authored more than 80 peer-reviewed articles, book chapters, and abstracts on topics related to cardiovascular pharmacotherapy and has gained national recognition as a key opinion leader in the areas of heart failure, anticoagulation, and coronary artery disease. He is also an active member of several organizations including the American College of Clinical Pharmacy, American College of Cardiology, and the Heart Failure Society of America.


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Disclosures In accordance with the Accreditation Council for Continuing Medical Education’s Standards for Commercial Support and the Accreditation Council for Pharmacy Education’s Standards for Commercial Support, ASHP requires that all individuals involved in the development of activity content disclose their relevant financial relationships. A person has a relevant financial relationship if the individual or his or her spouse/partner has a financial relationship (e.g. employee, consultant, research grant recipient, speakers bureau, or stockholder) in any amount occurring in the last 12 months with a commercial interest whose products or services may be discussed in the educational activity content over which the individual has control. The existence of these relationships is provided for the information of participants and should not be assumed to have an adverse impact on the content.

All faculty and planners for ASHP education activities are qualified and selected by ASHP and required to disclose any relevant financial relationships with commercial interests. ASHP identifies and resolves conflicts of interest prior to an individual’s participation in development of content for an educational activity. Anyone who refuses to disclose relevant financial relationships must be disqualified from any involvement with a continuing pharmacy education activity.

• Robert J. DiDomenico, Pharm.D., FCCP, declares that he has previously received an honorarium from Amgen, Inc. for authoring a drug monograph.


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• All other planners report no financial relationships relevant to this activity.


Robert J. DiDomenico, Pharm.D., BCPS‐AQ Cardiology, FCCP

Clinical ProfessorUniversity of Illinois at Chicago College of Pharmacy

Chicago, Illinois

Planned by ASHP Advantage and supported by an educational grant from Novartis Pharmaceuticals Corporation 1.0 CPE

Disclosures

• Robert J. DiDomenico, Pharm.D., FCCP, declares that he has previously received an honorarium from Amgen, Inc. for authoring a drug monograph.

• All other planners report no financial relationships relevant to this activity.

Learning Objectives

• Review the pathophysiology and demographics of chronic heart failure in the United States.

• Describe current strategies for effective pharmacologic and non‐pharmacologic management of patients with chronic heart failure.

• Compare the pharmacology and mechanism of action for medications used in managing chronic heart failure, including the role of new agents in therapy.

Heart Failure: The Cold Hard Facts

• 5.7 million adults in U.S. have heart failure (HF) (2012) – Prevalence will increase 46%

by 2030– 915,000 new cases annually– By age 40, lifetime risk = 1:5

adults• Hypertension (HTN) MAJOR

risk– 75% of HF cases have HTN– Lifetime risk 2X higher

• Mortality– ~30% at 1 year– ~50% at 5 years

• Hospitalizations– ~1 million annually– Mortality

• 28 days: 10.4%• 1 year: 29.5%

• Annual Cost– $30.7 billion (2012)

• Direct costs: $20.9B

Mozaffarian D et al. Circulation 2016; 133:e38‐360.

The “Average” Heart Failure Patient

Owan TE et al. N Engl J Med. 2006; 355:251‐9. Quiroz R et al. Am J Cardiol. 2014; 113:691‐6.

Mayo Clinic Get With The Guidelines

Characteristic HFrEF (53%) HFpEF (47%) HFrEF (55%) HFpEF (45%)

Age (yr) 72 74 67 68

Male gender (%) 65 44 61 47

Body habitus BMI: 29 kg/m2

BMI: 30 kg/m2

Weight: 86 kg Weight: 90 kg

HTN (%) 48 63 72 78

CAD (%) 64 53 36 24

AF (%) 28 41 21 19

DM (%) 34 33 38 42

Cr (mg/dL) 1.6 1.6 1.6 1.8

HFrEF=heart failure with reduced ejection fraction, HFpEF=heart failure with preserved ejection fraction

Heart Failure Pathophysiology


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In the neurohormonal model of heart failure, which of the following pathologic responses is associated with vasopressin?

A. ApoptosisB. Baroreceptor dysfunctionC. Collagen depositionD. Insulin resistance


From N Engl J Med; Schrier RW, Abraham WT; Hormones and hemodynamics in heart failure; 241; pp 577‐85. © (1999) Massachusetts Medical Society.

Reprinted with permission from Massachusetts Medical Society.

Angiotensin I

Angiotensin II

Aldosterone

Na/H2O reabsorption

Vasoconstriction

ACE

Bradykinin

Inactive

Neprilysin

AdrenomedullinANPBNP

Substance P

Vasodilation

Atrial stretch

ACE=angiotensin‐converting enzyme, ANP=A‐type natriuretic peptide, BNP=B‐type natriuretic peptide


• Remodelingo Afterload ventricular

hypertrophyo Preload ventricular

dilation Contractility o Contractility Afterload & Preload

Cycle perpetuates…

• Angiotensin II, aldosterone– Apoptosis, oxidative stress,

inflammation, fibrosis, insulin resistance, baroreceptor dysfunction

• Norepinephrine/epinephrine– Apoptosis, necrosis

• Vasopressin– Collagen deposition

Hemodynamic Model Neurohormonal Model

Parker RB et al. Chronic Heart Failure. In: DiPiro JT et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. New York, NY: McGraw‐Hill; 2014 (accessed 2016 Sep 4).

Management of Chronic Heart Failure

Heart Failure Management Strategies

Pharmacologic• ACE inhibitors, angiotensin

receptor blockers (ARBs)• Mineralocorticoid receptor

antagonists (MRAs)• Sacubitril/valsartan• Beta‐blockers• Nitrates/hydralazine• Diuretics• Ivabradine• Digoxin

Non‐pharmacologic• Device therapy

– Implantable cardioverter‐defibrillator (ICD)

– Cardiac resynchronization therapy (CRT)

• Care coordination systems• Sodium & water

restriction• Treatment of sleep

disorders• Weight loss• Physical activity

Yancy CW et al. J Am Coll Cardiol. 2013; 62:e147‐239. Yancy CW et al. J Am Coll Cardiol. 2016; pii:S0735‐1097(16)33024‐8.


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Atrial fibrillation would make a patient with HFrEF ineligible to receive which of the following medications?

A. EplerenoneB. Nitrates/hydralazineC. IvabradineD. Sacubitril/valsartan

Mechanism of Action: ACE InhibitorsAngiotensin I

Angiotensin II

Aldosterone

Na/H2O reabsorption

Vasoconstriction

ACE

Bradykinin

Inactive

Vasodilation

ACEI

X X • Vasodilation• Inhibit Na/H20 reabsorption• Slow disease progression• Increase bradykinin (cough)

ACEI=ACE inhibitor

Mechanism of Action: ARBsAngiotensin I

Angiotensin II

Aldosterone

Na/H2O reabsorption

Vasoconstriction

ACE

Bradykinin

Inactive

Vasodilation

ARBs

X

X

• Vasodilation• Inhibit Na/H20 reabsorption• Slow disease progression• No effect on bradykinin

Mechanism of Action: MRAsAngiotensin I

Angiotensin II

Aldosterone

Na/H2O reabsorption

Vasoconstriction

ACE

Bradykinin

Inactive

Vasodilation

MRAs

X

• Inhibit Na/H20 reabsorption• Slow disease progression

ACEI & ARBs for HFrEF: Outcomes

Garg R, Yusuf S. JAMA. 1995; 273:1450‐6. Lee VC et al. Ann Intern Med. 2004; 141:693‐704.

Drug ClassEndpoint

(vs. placebo)

Odds Ratio (OR)

95% CI P value

ACE inhibitors Mortality

Mortality orHF hospitalization

0.77

0.65

0.67‐0.88

0.57‐0.74

<0.001

<0.001

ARBs Mortality

HF hospitalization

0.83

0.64

0.69‐1.00

0.53‐0.78

0.05

<0.001

MRAs for HFrEF: Outcomes

Pitt B et al. N Engl J Med. 1999; 341:709‐17. Pitt B et al. N Engl J Med. 2003; 348:1309‐21. Zannad F et al. N Engl J Med. 2011; 364:11‐21.

0%

10%

20%

30%

40%

50%

RALES EPHESUS EMPHASIS

MRA

Placebo

All‐Cause Death

0%

10%

20%

30%

40%

50%

RALES EPHESUS EMPHASIS

MRA

Placebo

HF Hospitalization

P<0.001

P<0.001

P=0.008 P=0.03 P<0.001P<0.001


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Mechanism of Action: Beta‐blockers

Sympathetic Nervous System Activation

α1: Arteries β1: Heart

Vasoconstriction Afterload

Cardiac output

Tachycardia Cardiac output

CarvedilolMetoprololBisoprolol

X X

• Decrease heart rate• Decrease blood pressure• Increase cardiac output• Slow disease progression

Beta‐Blockers for HFrEF: Outcomes

Chatterjee S et al. BMJ. 2013; 346:f55.

All beta‐blockers

Duration <12 mos

Duration >12 mos

Odds Ratio 0 1.0 2.0

Beta‐blockers better Control group better

P<0.001

Mechanism of Action: Nitrates & Hydralazine Combination

From N Engl J Med, Hare JM, Nitroso‐redox balance in the cardiovascular system, 351, pp. 2112‐4. © (2004) Massachusetts Medical Society.

Reprinted with permission from Massachusetts Medical Society.

• Decreased preload & afterload

• Increased nitric oxide (NO) availability

• Decreased oxidative stress

Nitrates/Hydralazine for HFrEF: Outcomes

0%

10%

20%

30%

40%

50%

VHeFT 1 VHeFT 2 AHeFT

ISDN/Hyd Placebo Enalapril

Mortality

P=0.09

P=0.08

P=0.02

Cohn JN et al. N Engl J Med. 1986; 314:1547‐52. Cohn JN et al. N Engl J Med. 1991; 325:303‐10. Taylor AL et al. N Engl J Med. 2004; 351:204‐9.ISDN/Hyd=isosorbide dinitrate/hydralazine

American Heart Association, American College of Cardiology, Heart Failure Society of America Guideline Recommendations

• Class I (strong)– Benefit >>> risk

• Class IIa (moderate)– Benefit >> risk

• Class IIb (weak)– Benefit > risk

• Class III (moderate)– Benefit = risk

• Level of evidence (LOE)– A

• High‐quality, > 1 RCT

– B‐R: • Moderate quality, ≥ 1 RCT

– B‐NR• Moderate quality, ≥ 1

nonrandomized/observational studies

– C‐LD: Limited data– C‐EO: Expert opinion

Yancy CW et al. J Am Coll Cardiol. 2016; pii:S0735‐1097(16)33024‐8.

RCT=randomized controlled trial

Evidence‐Based Heart Failure Medications: Place in Therapy

Asymptomatic (Stage B)

• ACE inhibitor or ARB

PLUS

• Beta‐blocker

Class I, LOE A

Symptomatic (Stage C)

• African American, NYHA III/IV– Add ISDN/Hydralazine

• Class I, LOE A

• NYHA II‐IV, no CKD IV/V– Add MRA

• Class I, LOE A

• Diuretics: Class I, LOE C• Digoxin: Class IIa, LOE B

Yancy CW et al. J Am Coll Cardiol. 2013; 62:e147‐239.NYHA=New York Heart Association, CKD=chronic kidney disease


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Evidence‐Based Heart Failure Medications

The New Kids on the Block

Vardeny O et al. Clin Pharmacol Ther. 2013; 94:445‐8.

Mechanism of Action: Sacubitril/ValsartanAngiotensin Receptor‐Neprilysin Inhibitor (ANRI)

Sacubitril/Valsartan

Sacubitril(AHU377)(prodrug)

Valsartan

LBQ657

AT1 receptorblockade

Neprilysininhibition

Enzymatic cleavage

AT1=angiotensin type 1

Mechanism of Action: Sacubitril/ValsartanAngiotensin I

Angiotensin II

Aldosterone

Na/H2O reabsorption

Vasoconstriction

ACE

Bradykinin

Inactive

Neprilysin

AdrenomedullinANPBNP

Substance P

Vasodilation

Atrial stretch

Valsartan

X

X

Sacubitril

X

X

X

• Benefits of ARBs• Increased ANP, BNP

& other vasodilators

Sacubitril/Valsartan Pharmacology

Vardeny O et al. Clin Pharmacol Ther. 2013; 94:445‐8. King JB et al. Pharmacotherapy. 2015; 35:823‐37. Hanigan S, DiDomenico RJ. J Pharm Pract. 2016; 29:46‐57.

• Sacubitril– AHU377 LBQ657

• 2 – 4 hours

– LBQ657 not metabolized further

– Weak inhibitor of CYP2C9

• Valsartan– 40% higher exposure vs.

valsartan alone– Half‐life ~ valsartan alone

• Dose equivalence– 97 mg/103 mg =

valsartan 160 mg

PARADIGM HF Trial Design

McMurray JJ et al. N Engl J Med. 2014; 371:993‐1004.

• Adults with left ventricular ejection fraction (LVEF) ≤35‐40% • NYHA class II‐IV symptoms• BNP ≥ 150pg/mL or NT‐proBNP ≥600 pg/mL or HF

hospitalization in last 12 months • ACEI or ARB x 4 weeks• estimated Glomerular Filtration Rate (eGFR) ≥30 mL/min/m2

Single‐blind enalapril 10 mg BID x 2 weeks

Single‐blind sacubitril/valsartan 100 ‐ 200 mg BID x 4 – 6 weeks

Enalapril washout x 1 day

Enalapril 10 mg BID Sacubitril/valsartan 200 mg BID

NT‐proBNP=N‐terminal pro BNP

PARADIGM HF Outcomes1.0

0.6

0.4

0.2

360 720 1080


Enalapril

Sacubitril/valsartan

Days since randomization

CV death or HF hospitalization

(cumulative probab

ility)

HR 0.80 (95% CI 0.73 – 0.87)P<0.001

HR=hazard ratio


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PARADIGM HF Adverse Events

0%

5%

10%

15%

20%

Symptomatichypotension

Symptomatichypotension(SBP < 90)

Increased Cr >2.5 mg/dL

Increased Cr >3.0 mg/dL

Increased K+ >5.5 mEq/L

Increased K+ >6.0 mEq/L

Cough

Sacubitril/Valsartan EnalaprilP<0.001

P<0.001 P=0.007 P=0.10

P=0.15


P=0.007

P<0.001

Enalapril safer Sacubitril/valsartan safer

Mechanism of Action: Ivabradine

DiFrancesco D, Camm JA. Drugs. 2004; 64:1757‐65. Hanigan S, DiDomenico RJ. J Pharm Pract. 2016; 29:46‐57.

SA node

AV node

His‐PurkinjeSystem

Ventricular contraction

IfTransient calcium current

ICaT

Long‐lasting calcium currentICaL

IvabradineX

• Decreases heart rate• No effect on

contractility or blood pressure

If = hyperpolarization‐activated, cyclic nucleotide‐gated current, “funny” current

Ivabradine Pharmacology

• Bioavailability– 40%

• Tmax– 60 – 90 minutes

• Half‐life– Plasma = 2 hours– Effective t1/2 = 6 – 10

hours

• Metabolism– CYP3A4

• 80% of clearance

– Contraindication• Strong CYP3A4 inhibitors

– Avoid • CYP3A4 inducers • Moderate CYP3A4 inhibitors

Hanigan S, DiDomenico RJ. J Pharm Pract. 2016; 29:46‐57.Corlanor (ivabradine) prescribing information. Amgen, Inc. 2015 Apr.

Ivabradine in HFrEF: SHIFT Trial Outcomes

Swedberg K et al. Lancet. 2010; 376:875‐85.

0%

10%

20%

30%

40%

50%

CV death or HFhospitalization

All‐causemortality

CV mortality HF mortality All‐causehospitalization

CVhospitalization

HFhospitalization

IvabradinePlacebo

P<0.0001

P=0.09 P=0.13 P=0.01

P=0.003 P=0.0002 P<0.0001

CV=cardiovascular

SHIFT Adverse Effects

Swedberg K et al. Lancet. 2010; 376:875‐85.

Adverse EventIvabradine(n=3,232)

Placebo (n=3,260)

P value

Any adverse event 75% 74% 0.303Heart failure* 25% 29% 0.0005

Bradycardia*Symptomatic

Asymptomatic5%6%

1%1%

<0.0001<0.0001

Atrial fibrillation 9% 8% 0.012Phosphenes 3% 1% <0.0001

Blurred vision 1% <1% 0.042*Adverse event led to significant difference in drug withdrawal between groups

Sacubitril/Valsartan & IvabradineGuideline RecommendationsSacubitril/Valsartan (ANRI)• ACEI or ARB or ANRI +

β‐blockers & MRAs to decrease morbidity & mortality (Class I, LOE B‐R)

• ANRI in place of ACEI or ARB in HFrEF NYHA II‐III to further decrease morbidity & mortality (Class I, LOE B‐R)

• Avoid ANRI within 36 hours of last dose of ACEI and/or history of angioedema (Class III, LOE B‐R/C‐EO)

Ivabradine

• Ivabradine for HFrEF (LVEF ≤35%) on GDMT, including β‐blockers at maximally tolerated doses, in NSR with HR ≥70 bpm to reduce HF hospitalization (Class IIa, LOE B‐R)

Yancy CW et al. J Am Coll Cardiol. 2016; pii:S0735‐1097(16)33024‐8.

GDMT=guideline‐directed medical therapy,NSR=normal sinus rhythm, HR=heart rate


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Pharmacologic Therapy for Chronic Heart Failure

Yancy CW et al. J Am Coll Cardiol. 2013; 62:e147‐239.Yancy CW et al. J Am Coll Cardiol. 2016; pii:S0735‐1097(16)33024‐8.

+

Digoxin

+ Ivabradine

+ Diuretics

Sacubitril/valsartan

+ MRAs+/‐Nitrates/Hydralazine

ACEI or ARBs + BBsI

IIa

Class of Recommendation

A

B

C

Level of Evidence

Use Evidence‐Based Heart Failure Medications

• Initiate at low doses• Titrate to target dose not

“therapeutic response”– Dosing tables provided in

appendix

• Renal function threshold for inclusion in “anti‐RAAS” trials– Creatinine ~2.0 – 2.5 mg/dL– eGFR <30 mL/min/1.73 m2

• Monitoring– Vital signs & symptoms– ACE inhibitors & ARBs

• K+ & renal function – Within 1 – 2 weeks

– MRAs• K+ & renal function

– Within 2 – 3 days, then– At 7 days, then – Every month x 3, then– Every 3 months

• Education!!!Yancy CW et al. J Am

Coll Cardiol. 2013; 62:e147‐239.RAAS=renin–angiotensin–aldosterone system

Heart Failure Management Strategies

Pharmacologic• ACE inhibitors, angiotensin

receptor blockers (ARBs)• Mineralocorticoid receptor

antagonists (MRAs)• Sacubitril/valsartan• Beta‐blockers• Nitrates/hydralazine• Diuretics• Ivabradine• Digoxin

Non‐pharmacologic• Device therapy

– Implantable cardioverter‐defibrillator (ICD)

– Cardiac resynchronization therapy (CRT)

• Care coordination systems• Sodium & water

restriction• Treatment of sleep

disorders• Weight loss• Physical activity

Yancy CW et al. J Am Coll Cardiol. 2013; 62:e147‐239. Yancy CW et al. J Am Coll Cardiol. 2016; pii:S0735‐1097(16)33024‐8.

Which of the following nonpharmacologic interventions has the least supporting evidence?

A. Care coordinationB. Exercise trainingC. Sodium & water restrictionD. Treatment of sleep disorders

Device Therapy for HFrEF: Outcomes

Implantable Cardioverter Defibrillator (ICD)

• Survival vs. no ICD– <2 comorbidities

• HR 0.59 (95% CI 0.4‐0.87)

– ≥2 comorbidities• HR 0.71 (95% CI 0.61‐0.84)

– comorbidity associated with survival benefit (p=0.004)

Cardiac Resynchronization Therapy (CRT)

• CRT vs. OMT (n=2,355)– RR 0.73 (95% CI 0.62‐0.85)

• CRT‐ICD vs. ICD (n=5,184)– RR 0.83 (95% CI 0.72‐0.96)

• NYHA I & II > NYHA III & IV?

• Overall– RR 0.78 (95% CI 0.70‐0.87)

Wells G et al. CMAJ. 2011; 183:421‐9.Steinberg BA et al. J Am Coll Cardiol. 2014; 2:623‐9.

OMT=optimal medical therapyRR=relative risk

Care Coordination & the Pharmacist

• Care Coordination– Achieve GDMT & prevent

hospitalization– Plan includes

• GDMT goals• Management of

comorbidities• Timely follow‐up• Diet & exercise• Secondary prevention

• Pharmacist Impact & Role – All‐cause hospitalization

• OR 0.71 (95% CI 0.54‐0.94)

– HF hospitalizations

• OR 0.69 (95% CI 0.51‐0.94)

– Mortality• OR 0.84 (95% CI 0.61‐1.15)

– Collaborative > RPh‐directed– Multidisciplinary services

across the continuum of care

Koshman SL et al. Arch Intern Med. 2008; 168:687‐94. Yancy CW et al. J Am Coll Cardiol. 2013; 62:e147‐239. Milfred‐Laforest SK et al. J Card Fail. 2013; 19:354‐69.

Milfred‐Laforest SK et al. Pharmacotherapy. 2013; 33:529‐48.


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Nonpharmacologic Therapy for Chronic Heart Failure

Yancy CW et al. J Am Coll Cardiol. 2013; 62:e147‐239.

Sleep Sleep disorders

Na/H2O restrictionCare

coordination

Exercise training

ICD +/‐ CRTI

IIa

Class of Recommendation

A

B

C

Level of Evidence

A

B

Key Takeaways

• Drugs that block the pathologic neurohormonal actions in patients with HFrEF improve survival– Backbone of therapy: ACE inhibitors, ARBs, & beta‐blockers

• Sacubitril/valsartan & ivabradine represent 1st‐in‐class therapies that improve outcomes in HFrEF– Sacubitril/valsartan risk of CV death & HF hospitalization– Ivabradine reduces risk of HF hospitalization

• Pharmacists play an important role in medication management of patients with HFrEF – Associated with improved outcomes

Which of these changes in your practice are you likely to make after today’s presentation?

• Read recently released update to heart failure treatment guidelines

• Compare your organization’s protocols with recently released update to heart failure treatment guidelines

• Educate staff on the role for new agents to treat chronic heart failure

• Devise a monitoring plan for a patient with chronic heart failure

ACEI & ARB Doses for HFrEFDrug Class/Drug Initial Dose Maximum/Target Dose

ACE inhibitors:CaptoprilEnalaprilFosinoprilLisinopril

PerindoprilQuinaprilRamipril

Trandolapril

6.25 mg TID2.5 mg BID

5 – 10 mg once daily2.5 – 5 mg once daily

2 mg once daily5 mg BID

1.25 – 2.5 mg once daily1 mg once daily

50 mg TID10 – 20 mg BID40 mg once daily

20 – 40 mg once daily8 – 16 mg once daily

20 mg BID10 mg once daily4 mg once daily

Angiotensin receptor blockers:

CandesartanLosartanValsartan

4 – 8 mg once daily25 – 50 mg once daily

20 – 40 mg BID

32 mg once daily50 – 150 mg once daily

160 mg BID


MRA Doses for HFrEF

Drug Initial DoseMaximum/Target

Dose

Eplerenone

eGFR 30 – 49 mL/min/1.73m2

eGFR >50 mL/min/1.73m2

25 mg every other day

25 mg once daily

25 mg once daily

50 mg once daily

Spironolactone

eGFR 30 – 49 mL/min/1.73m2

eGFR >50 mL/min/1.73m2

12.5 mg every other day or once daily

12.5 – 25 mg once daily

12.5 – 25 mg once daily

25 mg once daily or BID


Beta‐Blocker Doses for HFrEF


Dose

Bisoprolol 1.25 mg once daily 10 mg once daily

Carvedilol IRCR

3.125 mg BID10 mg once daily

50 mg BID80 mg once daily

Metoprolol succinate12.5 – 25 mg once

daily200 mg once daily



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ISDN/Hydralazine Doses for HFrEF


Dose

ACEI or ARB intolerance or contraindication

ISDN

Hydralazine

20 – 30 mg 3 – 4 times daily

25 – 50 mg 3 – 4 times daily

120 mg in divideddoses

300 mg in divided doses

Adjunctive Therapy

ISDN/hydralazine (fixed dose)

20 mg/37.5 mg TID 40 mg/75 mg TID


Sacubitril/Valsartan & Ivabradine Doses for HFrEF


Dose

Sacubitril/Valsartan 24/26 mg BID 97/103 mg BID

Ivabradine5 mg BID with

meals7.5 mg BID with

meals

Entresto (sacubitril/valsartan) prescribing information. Novartis Pharmaceuticals Corp. 2015 Aug. Corlanor (ivabradine) prescribing information. Amgen, Inc. 2015 Apr.


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Self-assessment Questions The polling questions included in this presentation are listed below as a learner assessment tool. You may wish to note the correct answers and rationale as you follow along with the speaker.

1. In the neurohormonal model of heart failure, which of the following pathologic responses is associated with vasopressin?

a. Apoptosis b. Baroreceptor dysfunction c. Collagen deposition d. Insulin resistance

2. Atrial fibrillation would make a patient with HFrEF ineligible to receive which of the following

medications?

a. Eplerenone b. Nitrates/hydralazine c. Ivabradine d. Sacubitril/valsartan

3. Which of the following nonpharmacologic interventions has the least supporting evidence?

a. Care coordination b. Exercise training c. Sodium & water restriction d. Treatment of sleep disorders


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contemporary approaches to the management of chronic heart … · 2017. 10. 11. · contemporary...

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