How Can You Mend A Broken Heart? - PowerPoint Presentation

Slide1

How Can You Mend A Broken Heart?2017 Update on Heart Failure

Gwen Bartlett BS Pharm, Pharm D, BCPS, BCCCPAssistant Professor of Pharmacy PracticeHusson UniversityOctober 15, 2017Slide2

DisclosureI have no relevant financial or non-financial conflicts of interest to disclose. 2Slide3

Learning ObjectivesSummarize the evidence, utility, and limitations of established biomarkers in prevention, diagnosis, and prognosis of heart failure Discuss the mechanism of action, supporting clinical evidence, and appropriate use of  the newer chronic heart failure therapies. Design an appropriate patient-specific evidence-based pharmacotherapy plan for heart failure management.Slide4

Impact of Heart FailurePrevalence increased 5.7 million to 6.5 million 1/3 of the US adult population stage A HF Projected increased prevalence of 46% by 20305-year survival HF s/p AMI:2001 – 2010: 61% (up from 54%)Hospitalized HF eventsHF

rEF: 53% (highest proportion: black males)HFpEF: 47% (highest proportion: white females)Benjamin et al. Heart Disease and Stroke Statistics – 2017 Update: A Report From the American Heart Association. Circulation 2017; 135:e1-459Slide5

Key Guideline ChangesBiomarkersManagement of stage C HFrEFPrevention strategiesUpdates on HFpEFManaging cComorbidities (i.e., sleep apnea, anemia, HTN)Slide6

Stages in the Development of HF and Recommended Therapy by Stage.

Clyde W.

Yancy

et al. Circulation. 2013;128:e240-e327

Copyright © American Heart Association, Inc. All rights reserved.Slide7

BiomarkersSlide8

BNP and NT-proBNP McKie P.M. et al. NT-proBNP: The Gold Standard Biomarker in Heart Failure.

J Am Coll Cardiol 2016;68(12):Slide9

Level of Supporting Evidence for Use of Natriuretic Peptides in HFYancy et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guidelines for the Management of Heart Failure. Circulation

2017;e1-75.Slide10

A Difference of Opinion? Natriuretic Peptides

ACCF/AHA

ESC

Biomarker/ Application

Setting

COR

LOE

COR

LOE

Prevention in ‘at risk’ patients

Ambulatory

IIa

B-R

-

-

Diagnosis

or Exclusion of HF

Ambulatory,

Acute

I

A

IIa

C

Prognosis of HF

Ambulatory, Acute

I

A

-

-

Achieve

GDMT

Ambulatory

IIa

B--Serial measurements in chronic HFAmbulatoryIIbB--Guidance for ADHFAcuteIIbC--Myocardial injury Ambulatory, AcuteIAIASlide11

STOP-HF (St Vincent’s Screening TO Prevent Heart Failure)Inclusion:> 40 years old + 1 or moreHTN, hyperlipidemia; obesity (BMI > 30); vascular disease; diabetes mellitus; arrhythmia requiring therapy; mod to severe valve disease

Exclusion:LV dysfx or h/o HF

Ledwidge

et al, STOP-HF Randomized trial

. JAMA 2013;31091:66-74.

OR 0.59 [0.38 – 0.9], p = 0.01

Control group: 75

%

with

1

○

endpoint had BNP > 50

pg

/mLSlide12

STOP-HF Secondary Outcomes(St Vincent’s Screening TO Prevent Heart Failure)

MACE = Stroke/TIA; PE/DVT; AMI;HF; or Arrhythmia

Ledwidge et al,

STOP-HF Randomized trial. JAMA

2013;31091:66-74.

All participants

Participants with BNP ≥ 50

pg

/mLSlide13

PONTIAC(NT-proBNP selected PreventiOn of cardiac eveNts in a populaTion of d

Iabetic patients without A history of Cardiac disease)300 patients: Inclusion: Type 2 DM for ≥ 6 months + > 18 years old + NT-proBNP > 125

pg/mLExclusion

h/o cardiac diseaseECG with a fib, ST-T-wave abnormalities or BBB, low LVEF, wall motion abnormalties

, valve dysfxNT-proBNP

identified high-risk and triggered up-titration of RAAS inhibitor +

β

-blocker

Primary Endpoint:

Hospitalization or CV death

Huelsmann

M et al. PONTIAC Trial.

J Am

Coll

Cardiol

2013; 62:1365-72. Slide14

Thresholds for BNP Are DIFFERENT! BNPNT-proBNP

Ambulatory/Outpatient50 pg/mL125 pg/mLAcute/Inpatient100 pg/mL

300 pg/mL

Schreiber D et al.

Natriuretic Peptides in Congestive Heart Failure. Medscape. Updated 9/2016

Ponikowski

et al.

2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

.

Eur

Heart J

2016:37:2129-2200. Slide15

Limitations of BNP and NT-proBNPDiagnosis:Limited in HFpEFInfluenced by LVEF, age, sex, renal function, Na+ levels, BMI, and other comorbiditiesPrognosis:BNP elevation associated with increased mortality and hospital readmissions

Guiding therapy:Limited evidence supporting Recent GUIDE-IT trial terminated due to futilityRubattu et al. Resetting the Neurohormonal Balance in Heart Failure: the Relevance of the Natriuretic Peptide System to the Clinical Management of Patients with HF

. Heart Fail Rev

2017;22;279-88Slide16

Update in Managing Stage C HFrEF Is it a “PARADIGM SHIFT”?? Slide17

Stages in the Development of HF and Recommended Therapy by Stage.

Clyde W.

Yancy

et al. Circulation. 2013;128:e240-e327

Copyright © American Heart Association, Inc. All rights reserved.Slide18

NEW Algorithm: HFrEF Stage C & DSlide19

Reiterated from 2013:Stage C HFrEFI

IIa

IIb

III

Recommendation

A

The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic

HFrEF

to reduce morbidity and mortality

A

The use of ARBs to reduce morbidity and mortality is recommended in patients with prior or current symptoms of chronic

HFrEF

who are intolerant to ACE inhibitors because of cough or angioedema.

Yancy

et al.

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

.

Circulation

2017; 136:e137-61. Slide20

ARNI (angiotensin receptor blocker / neprilysin inhibitor)Slide21

PARADIGM HF(Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart

Failure)8442 stable class II-IV HFrEF patients (LVEF < 40%)Compared LCZ-696 to enalapril 10 mg PO BIDComposite endpoint:

HF hospitalization or CV deathTrial stopped early 2nd

overwhelming efficacy

McMurray et

al.

Angiotensin–

Neprilysin

Inhibition versus

Enalapril

in Heart

Failure

.

N

Engl

J

Med

2014;371:993-1004

26.5%

21.8%Slide22

The BIG BANG!! Stage C HFrEFI

IIa

IIb

III

Recommendation

A

A

B-R

The clinical strategy of inhibition of the renin-angiotensin system with

ACE inhibitors

OR

Angiotensin receptor blockers

OR

Angiotensin receptor/

neprilysin

inhibitor

in conjunction with evidence-based

β

-blockers and aldosterone antagonists in selected patients is recommended for patients with chronic HFrEF

to reduce morbidity and mortality.Yancy et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation 2017; 136:e137-61. Slide23

The BIG BANG!! Stage C HFrEFI

IIa

IIb

III

Recommendation

ARNI: B-R

In patients with chronic symptoms

HF

r

EF

NYHA class II or III who tolerate an ACE inhibitor or ARB,

replacement by an ARNI is recommended to further reduce morbidity and mortality.

HARM

B-R

ARNI should

NOT BE

administered

concomitantly with ACE inhibitors or within 36 hours

of the last dose of an ACE inhibitor.

HARMC-EO

ARNI should

NOT BE

administered to patients with a history of

angioedema

.

Yancy

et al.

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

.

Circulation

2017; 136:e137-61. Slide24

sacubitril/valsartanZile et al. Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol

2016;68(22):Natriuretic Peptide System

Heart Failure

Renin Angiotensin System

Pro-BNP

Angiotensinogen

BNP

NT-

proBNP

Inactive Fragments

Sacubitril

/Valsartan

Sacubitril

Valsartan

Neprilysin

Angiotensin I

Angiotensin II

AT1 ReceptorSlide25

sacubitril/valsartan

IndicationFixed dose combination: sacubitril (neprilysin inhibitor) + valsartan (ARB) is indicated to reduce the risk of CV death and HF hospitalization in patients with HFrEFDosageStart with 49/51 mg two times daily.

Double the dose after 2 – 4 weeks as tolerated to a maintenance dose of 97/103 mg two times daily.Renal/Hepatic

ImpairmentFor patients

not currently taking an ACEI or ARB, or for those with severe renal impairment (i.e., eGFR < 30 mL/min) or moderate hepatic impairment, begin with 24/26 mg two times daily

Switching from an ACE

inhibitor

Stop

ACE inhibitor fro 36 hours prior to starting treatment.

Contraindications

History

of angioedema related to previous ACE inhibitor or ARB, concomitant use of ACE I, concomitant use of

aliskiren

in patient with diabetes. WARNING: hyperkalemia, pregnancy

Adverse Effects

Hypotension,

hyperkalemia, cough, dizziness, renal failure, and angioedema (i.e., 0.5%

sacubitril

/valsartan versus 0.2%

enalapril)Entresto® package labeling: Last revised 8/2015Slide26

Biomarker in Presence of ARNI

Rubattu et al. Resetting the Neurohormonal Balance in Heart Failure: the Relevance of the Natriuretic Peptide System to the Clinical Management of Patients with HF. Heart Fail Rev

2017;22;279-88.Slide27

ARNI trials PARAGON-HFEvaluating sacubitril/valsartan in HFpEFAnticipate publication in 2019TRANSITIONEvaluating in-hospital initiation when admission for ADHFPARADISE-MI

Evaluating effectiveness post MI to reduce HF eventsSlide28

Ivabradine(Hyperpolarization-activated cyclic nucleotide gated channel)Slide29

SHIFT(Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial)

6558 stable class II to IV HFrEF (LVEF ≤ 35%)Compared ivabradine to placebo (~ 90% on β-blocker)Composite endpoint: HF hospitalization or CV death

Atrial fib: ivabradine

5% versus placebo 3.9 %

Swedberg

K et al.

Ivabradine

and outcomes in Chronic Heart Failure (SHIFT): A

Randomised

, placebo-controlled study.

Lancet

2010;

376:875-85.

https

://

www.corlanorhcp.com/static/corlanorhcp/pdfs/clinicalfact sheet.pdfSlide30

And the SHIFT: Role of IvabradineStage C HFrEFI

IIa

IIb

III

Recommendation

B-R

Ivabradine

can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II – III) stable chronic

HF

r

EF

(LVEF ≤ 35%) who are receiving GDMT, including a beta-blocker at maximum tolerated dose, and who

are in sinus rhythm with a heart rate of 70 bpm or greater at rest

.

Yancy

et al.

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

.

Circulation

2017; 136:e137-61.

GDMT: Guideline-direct management and therapySlide31

ivabradineKoruth JS et al. The Clinical Use of Ivabradine. J Am

Coll Cardiol 2017; 70(14):1777-84. Slide32

ivabradineCorlanor® package labeling: Last revised 1/’2017

Indication

Ivabradine

is a HCN channel blocker indicated to reduce the risk of HF hospitalization in patients with stable, symptomatic chronic heart failure with LVEF ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 bpm and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.

Dosage

Start with 5 mg two

times

daily.

After 2 weeks. Adjust dose based on heart rate. The maximum dose is 7.5 mg two times daily. Conduction defects or risk of hemodynamic compromise with bradycardia: start at 2.5 mg two time daily. HR > 60 bpm: ↑ by 2.5 mg BID; HR 50-60 bpm: continue; HR < 50 or signs and symptoms of bradycardia, ↓ by 2.5 mg BID or if at 2.5 mg BID, DC

Renal/Hepatic

CYP3A4 substrate:

avoid moderate and strong inhibitors or inducers. Contraindicated in severe hepatic impairment (Child-Pugh C). No data available for severe renal insufficiency (

eGFR

< 15 mL/min).

Contraindications

ADHF;

BP < 90/50 mm Hg; SSS or 3

rd

degree AV block without PPM; Resting HR < 60 bpm prior to initiation; Severe hepatic impairment; Pacemaker dependence

. WARNING: pregnancy (Fetal toxicity)Adverse EffectsFetal toxicity; Atrial fibrillation; Bradycardia + conduction disturbances; Phosphenes (visual light disturbances)Slide33

The Connection Between Heart Rate and Mortality in HFRetrospective cohort GWTG-HF clinical registry data for 46,217 Medicare claimsMedian age 80 y.o., primarily Caucasion, ~ 80% HTN, ~ 50% CAD; ~ 55% h/o HFNSR cohort; 30 day primary outcome for each 10 bpm increment HR < 75 bpm 19.2% higher risk mortality (HR 1.192; 95% CI 1.075-1.322; p = 0.0008)HR ≥ 75 bmp 30% higher risk mortality (HR 1.3; 95% CI 1.219-1.385; p < 0.0001)

Laskey WK et al. Heart Rate at Hospital Discharge in Patients With Heart Failure is Associated with Mortality and Rehospitalization. J Am Heart

Assoc 2015;4: e1-19.

n

= 26,020p < 0.0001 T1 to T3 Slide34

Relative Benefits of Evidence-Based Therapies in HFrEFFonarow et al.

Potential Mortality Reduction With Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure. JAMA Cardiol 2016;1(6):714-7.

CRT – cardiac resynchronization therapy; ICD – implantable cardioverter defibrillator

a Standardized to 12 months

b Benefit of ARNI therapy incremental to that achieved with ACE therapy. All other medications showed, benefits are based on comparisons to placebo.Slide35

Patient Management Tools: 2017 HF GWTGACHIEVEMENT MEASUREACE/ARB or ARNI at discharge (Updated)QUALITY MEASUREARNI at discharge (New)Reporting MeasuresIvabradine at discharge

(New)Slide36

PreventionSlide37

Stages in the Development of HF and Recommended Therapy by Stage.

Clyde W.

Yancy

et al. Circulation. 2013;128:e240-e327

Copyright © American Heart Association, Inc. All rights reserved.Slide38

First Symptoms = SENTINEL EVENTAmmar KA, Prevalence and Prognostic Significance of Heart Failure Stages. Circulation 2007; 115:1563-1570. Slide39

Risk Factors Matter!!!! Risk factors:HypertensionDiabetes mellitus

ObesityAhmad FS et al. Hypertension, Obesity, Diabetes and Heart Failure-Free Survival. J Am Coll Cardiol HF 2016; 4:911-9Slide40

Prevention of Incident HF: Control BPI

IIa

IIb

III

Recommendation

B-R

In patients at increased risk, stage A HF, the optimal blood pressure in those with hypertension should be

less than 130/80 mm Hg

Yancy

et al.

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

.

Circulation

2017; 136:e137-61.

* Will be consistent with new ACC/AHA Hypertension panel guidelines upcoming in 2017: SPRINT

trial

Class IA recommendation for Stage C

HF

r

EF

and

HFpEF as well!! Slide41

New Focus is PREVENTION!Stage A (i.e., asymptomatic without LV dysfx)HypertensionDiabetes mellitusCoronary artery disease ObesityHF can be prevented and progression to HF interruptedBNP or NT-proBNP screening to refine risk prediction

Yancy et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guidelines for the Management of Heart Failure. Circulation 2017;e1-75.Slide42

Update in Managing HFpEFSlide43

Prevention of Incident HF: Control BPI

IIa

IIb

III

Recommendation

B-R

In appropriately selected patients with

HFpEF

(with EF ≥ 435%, elevated BNP levels or HF admission within 1 year,

eGFR

> 30 mL/min, creatinine < 2.5 mg/

dL

, potassium < 5.0

mEq

/L), aldosterone receptor antagonists might be considered

to decrease hospitalization.

Yancy

et al.

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

.

Circulation

2017; 136:e137-61. Slide44

TOPCAT (Treatment Of Preserved Cardiac Function Heart Failure with an AldosTerone Antagonist)3345

HFpEF with HF hospitalization in past year or elevated NP past 30 dayLVEF > 45%at least 1 sign + 1 symptomSpironolactone 15 – 45 mg Daily or placeboComposite Outcome: HF hospitalization, aborted cardiac arrest, CV death

Pitt et al.

Spironolactone for Heart Failure with Preserved Ejection Fraction.

New Engl J Med 2014; 370(15):1383-92

Primary Endpoint:

HF Hospitalization, aborted cardiac arrest, or

CV deathSlide45

TOPCATPfeffer et al. Regional Variation in Patients and Outcome in the TOPCAT tria

l. Circulation 2015; 131:34-42. de Denus S et al. Spironolactone Metabolites in TOPCAT – New Insights into Regional Variation. New Engl J Med 2017.; Slide46

HFpEFNo specific therapies available to reduce morbidity and mortality in HFpEFAggressively manage cardiac comorbidities which exacerbate diastolic dysfx: HTN, CAD, and A fibTreat non-cardiac comorbidities: obesity, CKD, sleep apnea, iron deficiency anemia, and encourage lifestyle modificationsSlide47

Iron DeficiencySlide48

IRONOUT-HF(IRON Repletion Effects on Oxygen UpTake in Heart Failure Trial)

225 stable patients HFrEF NYHA II – IV symptomsIron polysaccharide 150 mg PO BID x 16 wksPrimary endpoint: Change in peak oxygen uptake (VO2)Outcome: High-dose

ORAL iron did not improve exercise capacity: assessed by VO2

, 6-minute walk distance, and QOL assessed by KCCQ score

Lewis et al. Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency.

JAMA

2017; 317(19):1958.66Slide49

https://www.heart.org/HEARTORG/Conditions/HeartFailure/Heart-Failure-Guidelines-Toolkit_ UCM_491412_SubHomePage.jspSlide50

ConclusionsData suggests biomarkers may be valuable in identify high-risk patients in order to PREVENT development of heart failureARNI therapy is now considered a 1st line therapy in selected patients and is a 2017 GWTG-HF Achievement measureHypertension management remains the most important modifiable risk factor to PREVENT development of HFSlide51
Slide52

Self-Assessment Question #1 J.J., a 78 y.o. male, is seen in HF clinic for his monthly follow up appt for clinical reassessment and potential medication titration. J.J. has Stage C heart failure (LVEF 35%) with NYHA III symptoms. Due to ongoing symptoms, two weeks prior the decision was made to discontinue lisinopril and convert to an ARNI. Allergies

: seasonal rhinitisCurrent HF meds include: metoprolol succinate 100 mg orally Dailysacubitril/valsartan 49/51 mg orally BID furosemide 40 mg orally BIDSlide53

Self-Assessment Question #1Of the following biomarkers, which has the strongest supporting evidence and would be least impacted by the initiation of an ARNI? Pre-proBNPANPNT-proBNP

CNPRationale: Answer C is correct. Both BNP and NT-proBNP are considered the gold standard biomarkers of HF. Pre-proBNP is an intracellular precursor peptide. As such, it would not likely be measurable in the blood (Answer A is incorrect). Both active natriuretic peptides, ANP and CNP are measurable in the plasma. Currently, however, there is limited data describing the utility of these biomarkers in this setting (Answer B and D are incorrect). Based on available data, the interpretation of NT-

proBNP appears to be unaffected by neprilysin

inhibition (Answer C is correct). Because BNP is metabolized by neprilysin, sacubitril

inhibition of this enzyme results in a modest increase in serum BNP (i.e., 200 pg/mL), but less than that of acute cardiac decompensation. If only a BNP assay is available for disease monitoring in a given clinical setting, it can still be useful for disease monitoring. A new steady state BNP level should be achieved approximately 1 month after

sacubitril

initiation. This BNP serum level can be used as the new “higher” baseline level

. Slide54

Self-Assessment Question #2The following 4 patients with HF and comorbidities including type 2 DM and ASCVD have been stable for the past 6 months on ACEI and beta blocker therapy. For which patient does current evidence strongly support consideration of initiation of an ARNI (angiotensin receptor blocker/neprilysin inhibitor)? Stable Stage A HFrEF with NYHA functional class I symptomsStable Stage C

HFrEF with NYHA functional class II symptomsStable HFpEF with NYHA functional class III symptomsHospitalized HFpEF with NYHA functional class IV symptomsRationale:

Answer B is correct. The evidence for the recommendation to consider an ARNI is a result of the findings from the PARADIGM-HF trial which included OUTpatients

with LVEF < 35% and NYHA functional classes II – IV; in fact, ~ 70% of patients enrolled were classified as NYHA functional class II (Answer B is correct). Although the PARAGON-HF trial is evaluating patients with HFpEF

, at this point there is insufficient data to support a recommendation in this population (Answers C and D are incorrect). Slide55

Self-Assessment Question #3A.M., a 69 y.o. female 5’ 6” 172 lbs (78 kg), is seen in HF clinic for follow up. A.M. continues to suffersymptoms of HF despite appropriate medical therapy. A.M.’s current HF meds include: metoprolol succinate 200 mg orally Dailyvalsartan 40 mg orally BID

furosemide 40 mg orally BID spironolactone12.5 mg orally DailyAllergies: lisinopril (angioedema)Chem panel: Na + 134 | K + 4.8 | Cl - 102 | CO 2 - 26 | BUN 24 | SCr 1.6 |Glucose 126Slide56

Self-Assessment Question #3The nurse practitioner stops you in the hall and asks about conversion to ARNI. Which of the followingis the most appropriate response?Based on the serum K + level, it would be appropriate to consider converting Based on the serum creatinine, it would be inappropriate to consider converting

Based on the allergy history, it would be inappropriate to consider convertingHold the valsartan for 36 hours; then proceed with converting to the ARNI.Rationale: Answer C is correct. Although ANRI therapy can be considered in patients with renal impairment, hyperkalemia, and cough associated with ACEI therapy, it is contraindicated to utilize

in patients with ACEI-associated or ARB-associated angioedema (Answer D is incorrect

). Recognizing that ARBs do not inhibit kininase

thus resulting in lower incidence of cough and angioedema, the new 2017 guidelines do provide a level I class of recommendation to use ARBs in the setting of

ACEI-associated angioedema

with the precaution that there is some potential for cross-reactivity. Although AM does

have renal

impairment (

estClCr

~ 30 mL/min) there are recommendations supporting

initiating

sacubitril

/valsartan

initiation, but at a lower dose of 24/26mg (Answer B is

incorrect)Slide57

Self-Assessment Question #3Rationale: Answer C is correct. Although ANRI therapy can be considered in patients with renal impairment, hyperkalemia, and cough associated with ACEI therapy, it is contraindicated to utilize in patients with ACEI-associated or ARB-associated angioedema (Answer C is correct). Recognizing that ARBs do not inhibit kininase thus resulting in lower incidence of cough and angioedema, the new 2017 guidelines do provide a level I class of recommendation to use ARBs in the setting of ACEI-associated angioedema with the precaution that there is some potential for cross-reactivity. Although AM does have renal impairment (estClCr

~ 30 mL/min) there are recommendations supporting initiating sacubitril/valsartan initiation, but at a lower dose of 24/26mg (Answer B is incorrect). Certainly drugs which impact the RAAS system all have the potential to augment serum K+. However, there is some suggestion that the incidence of hyperkalemia may, in fact, be lower with an ARNI than ACEI. It does

merit monitoring of serum K+ levels, but this would not be justification not to initiate the drug (Answer

A is incorrect). The recommendation and package labeling require ACEI to be held for 36 hours prior to

initiating an ARNI, but this doesn’t apply to the ARBs (Answer D is incorrect).Slide58

Review of Classifications of Heart Failure