Strategies to Optimize Heart Failure Treatment: New Insights and - - PowerPoint PPT Presentation

Strategies to Optimize Heart Failure Treatment: New Insights and Challenges

Harleen Singh, Pharm.D.,BCPS-AQ Cardiology, BCACP Clinical Associate Professor OSU/OHSU College of Pharmacy

Objectives

• Examine evidence-based guidelines for the management
• f heart failure with reduced ejection fraction, including

the role of newer agents

• Recognize the challenges associated with up-titration of

HF medications

• Design individualized therapy to optimize treatment
• Describe the key self-care interventions in the

management of HF

Disclosures

Presenter of this CE have nothing to disclose

GDTM in the Outpatient Setting

J Am Coll Cardiol 2018;72:351–66)

GDTM in HFrEF

J Am Coll Cardiol 2018;72:351–66)

Classification of Heart Failure

Classification EF (%) Description Heart failure with reduced ejection fraction (HFrEF) ≤40

• Systolic HF
• Randomized clinical trials have mainly enrolled

patients with HFrEF, and it is only in these patients that efficacious therapies have been demonstrated to date Heart failure with preserved ejection fraction (HFpEF) ≥50

• Diastolic HF
• Diagnosis of HFpEF is challenging because it is

largely one of excluding other potential noncardiac causes of symptoms suggestive of HF

• To date, efficacious therapies have not been

identified HFpEF, borderline 41-49

• These patients’ characteristics, treatment patterns,

and outcomes appear similar to those with HFpEF HFpEF, improved >40

• Patients with improved or recovery in EF may be

clinically distinct from those with persistently preserved or reduced EF

• Further research is needed to better characterize

these patients

10 Principles for Successful Treatment of HF

Yancy et al. JACC VOL. 71,NO.2,2018

Key: Class I recommendation Class II recommendation

HFrEF Stage C Treatment

ACEI/ARB AND Beta blocker with diuretic as needed

For patients with persistent volume

• verload,

NYHA class II-IV For persistently symptomatic African Americans, NYHA class III-IV For patients stable on ACEI/ARB, NYHA class II-III For patients with eGFR ≥ 30 mL/min/1.72 m2, K+ <5.0 mEq/dL NYHA class II-IV For patients with resting HR ≥ 70,

• n maximally

tolerated beta blocker dose in sinus rhythm, NYHA class II-III

Titrate Add Switch Add Add

Diuretics

Hydralazine + Isosorbide dinitrate

ARNI Ivabradine Aldosterone Antagonist

Yancy et al. JACC VOL. 71:2 ,2018

Diuretics

Nat Rev Cardiol. 2015;12(3):184-92.

~25% ~5%

Loops:

• Furosemide
• Torsemide
• Bumetanide

Thiazides:

• Hydrochlorothizide
• Chlorthalidone
• Chlorthiazide
• Metolazone

Aldosterone Antagonists:

• Spironolactone
• Eplerenone

Other K-Sparing:

• Amiloride
• Triamterene

For patients with persistent volume

• verload, NYHA class II-IV

Titrate Diuretics

Diuretics: Place in Therapy

HFrEF Stage C Treatment ACEI/ARBs and beta blockers with diuretic as needed Yancy et al. JACC VOL. 71:2 ,2018

Pharmacologic Properties of Loops

Property Furosemide Torsemide Bumetanide Relative potency 1x 2x 40x Bioavailability (%) 10-100 80-100 80-100 Oral/IV dosing 2:1 1:1 1:1 Time to onset (min) 60 60 30-60 Oral peak serum concentration (h) 1 1 1-2 Absorption affected by food Yes No Yes Average half-life (h) 2 3.5 1-1.5 Duration of effect (h) 6-8 6-16 4-6 Decreased kaliuresis No Yes No

Am Heart J 2015;169:323-33

Diuretics: Initiation and Titration

Select initial loop diuretic dose based on:

• Diuretic naïve
• Renal function
• Titrate doses to response over days to weeks
• May reduce diuretic doses in the setting of

titrating ACEI, ARBs, or ARNI

• Monitor: blood pressure, electrolytes, and renal

function both after initiation and titration Patients who have received doses of furosemide equivalent to 120 mg twice daily consider:

• Changing to a different loop diuretic
• Adding a thiazide-like diuretic
• Monitor blood pressure, electrolytes, and

renal function both after initiation and titration

Diuretics

Yancy et al. JACC VOL. 71:2 ,2018

Dose-Response Relationship

Normal Heart Failure

Decreased max response

Elevated diuretic threshold (resistance)

Ceiling Dose

J Card Fail. 2014;20(8):611-22

“Steep” part of dose-response curve

Patients with heart failure require a higher serum diuretic concentration to elicit the same diuretic response (diuretic resistance) and have diminished responses to ceiling doses of loop diuretics.

Mechanisms of loop diuretic resistance

• Nat. Rev. Cardiol. doi:10.1038/nrcardio.2014.215

Metolazone

Pharmacokinetics Metolazone Hydrochlorothiazide Bioavailability 90-95% 65-75% Onset of action ~60 min 2 hours Elimination half-life 6-20 hours 6-15 hours Duration of action >24 hours 6-12 hours

• Metolazone is most commonly prescribed for

combination therapy in the U.S.

• Retains efficacy in advanced renal failure
• However, other thiazides at equipotent doses are likely

to have the same synergistic effects

J Am Coll Cardiol. 2010;56(19):1527-34

Timing of CDT Doses

• Pre-dosing of oral metolazone 30-60 min prior to

furosemide is common practice – Increased regimen complexity – Inconvenient

• No published clinical studies compared pre-dosing

to simultaneous dosing

• Onset of metolazone is unlikely to be clinically

significant with chronic treatment once steady-state is achieved

• TD (with longer duration of action) maintains

diuresis after short acting LD has worn out

J Am Coll Cardiol. 2010;56(19):1527-34

TX

VAD CRT ICD

Beta blocker ACEI/ARB MRA

Ivabradine

ARNI

Digoxin H-ISDN HFrEF: The Building Blocks of Therapy

GDMT RR Reduction in Mortality NNT for Mortality Reduction (Standardized to 36 months) RR Reduction in HF Hospitalizations ACEI or ARB 17% 26 31% Beta blocker 34% 9 41% Aldosterone antagonist 30% 6 35% Hydralazine/nitrate 43% 7 33% ARNI 20% 21* 21%

*Standardized to 27 months, active comparator (enalapril) vs placebo

Magnitude of Benefits Demonstrated in RCTs

JACC 2013;62:e147-239

HFrEF – ACEI

ACEI Doses

Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose Achieved in Clinical Trials Captopril Capoten 6.25mg TID 50mg TID 122.7 mg/day Enalapril Vasotec 2.5mg BID 20mg BID 16.6 mg/day Fosinopril Monopril 5-10mg daily 80mg daily N/A Lisinopril Zestril/ Prinivil 2.5-5mg daily 20mg daily *4.5 mg/day (low dose ATLAS) 33.2 mg/day (high dose ATLAS) Quinapril Accupril 5mg BID 80mg daily N/A Ramipril Altace 1.25-2.5mg daily 10mg daily N/A Trandolapril Mavik 1mg daily 4mg daily N/A

*No difference between mortality between high and low dose groups, but 12% lower risk of death or hospitalization in high dose group vs. low dose group.

JACC 2013;62:e147-239

HFrEF – ARB

ARB Doses

Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose Achieved in Clinical Trials Candesartan Atacand 4-8 mg daily 32 mg daily 24 mg/day Losartan* Cozaar 12.5-25 mg daily 150 mg daily 129 mg/day Valsartan Diovan 40 mg BID 160 mg BID 254 mg/day

*Not FDA approved for HF

JACC 2013;62:e147-239

ACEI/ARB: Initiation and Titration

ACEI/ARB Select an initial dose of ACEI/ARB Consider increasing dose every 2 weeks Monitor BP, renal function and potassium

Barriers to titration

• Worsening renal function
• Hyperkalemia
• Bilateral renal artery stenosis
• Symptomatic Hypotension
• Overdiuresis
• Other medications

Monitoring

• SCr and K assessed within 1-2 weeks of

initiation or dose increase

Yancy et al. JACC VOL. 71:2 ,2018

What we know about RAASi dose response?

Trial Drug Groups N Age, years Male, % Follow- up, months ATLAS1 Lisinopril LD = 2.5-5.0 mg daily HD = 32.5-35 mg daily 1,596/ 1,568 64 79 46 HEAAL2 Losartan LD = 50 mg daily, HD = 150 mg daily 1,919/ 1,927 66 71 56

• 1. Packer M, et al. Circulation 1999;100:2312-2318
• 2. Konstam MA, et al. Lancet 2009;374:1840-1848

• Circulation. 1999;100:2312-2318

Lancet 2009; 374: 1840–48

ACEI/ARB with Renal Impairment

Generally considered safe when:

• SCr <3.0 mg/dL
• Renal impairment (eGFR 30-60 mL/min/1.73m2)

Should we stop ACEI/ARB in CKD stage 4 and 5?

Hyperkalemia: Is It Real? Pseudohyperkalemia

• Delayed processing

– Central vs. local labs – Traumatic draw

• Presence/absence of hyperglycemia

Target Serum Potassium Ranges in HF

• Heart Failure

– 4.0-5.0 mEq/L1,2 – 4.5-5.5 mEq/L3

• Expert opinion
• Hyperkalemia

– 5.0 vs. 5.5 vs. 6.0 mEq/L

1.

• Circulation. 2004,110(5):588-636.

2. Arch Intern Med. 2000;160(16):2429-2436. 3. J Am Coll Cardiol. 2004;43(2):155-161.

2 3 4 5 6 7

Serum Potassium (mEq/L)

Hyperkalemia Hypokalemia Normal

Mortality by Prior RAAS Inhibitor Dose

9.8 13.7 5.0 4.1 20.3 27.7 10.1 8.2 22.4 30.1 13.1 11.0 5 10 15 20 25 30 35 CKD Stage 3-4 n = 43,288 Heart Failure n = 20,529 Diabetes n = 79,087 Total n = 201,655

Percent of Patients

Maximum Dose Sub-Maximum Dose Discontinued

Am J Manag Care. 2015;21:S212-S220.

Clinical Dilemma

Continue RAAS Inhibitor Accept Hyperkalemia Discontinue RAAS Inhibitor Sacrifice Mortality Benefit

Hyperkalemia

• Discontinue potassium supplements
• Evaluate concomitant use of potassium-

sparing diuretics

• Dietary restrictions (salt substitutes)
• Temporary discontinuation of either ACEI or

ARB therapy

Hypotension

• Asymptomatic Hypotension

– No action is required for asymptomatic hypotension provided there is no evidence of renal hypoperfusion

• Symptomatic Hypotension

– Flexible diuretic dosing or dose reduction – Consider advising patient to take once-daily doses of ACEI in divided doses – Consider discontinuing or reducing the dose of other concomitant medications that may affect blood pressure (e.g., calcium antagonists, nitrates) – Initiate β-blockers before ACEI

HFrEF – Beta Blockers

Beta Blocker Doses

Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose Achieved in Clinical Trials Bisoprolol Zebeta 1.25 mg daily 10 mg daily 8.6 mg/day Carvedilol Coreg 3.125 mg BID 25 mg BID *50 mg BID 37 mg/day Metoprolol succinate Toprol XL 12.5-25 mg daily 200 mg daily 159 mg/day

*If patient is >85 kg

JACC 2013;62:e147-239

Beta-Blockers: Initiation and Titration

Beta blockers

Select an initial dose of beta blockers Consider increasing dose every 2 weeks Monitor BP, HR and signs

• f congestion

Barriers to titration

• Symptomatic hypotension/bradycardia
• Overdiuresis
• Other medications
• Autonomic dysfunction
• Transient worsening of HF symptoms
• Dyspnea, fatigue, or dizziness

Monitoring

• Fatigue, dyspnea, dizziness, HR

Yancy et al. JACC VOL. 71:2 ,2018

B-Blocker Dose-response outcomes

J Am Coll Cardiol 2017;69:2542–50)

Clinical Scenarios

Scenario I: Which beta blocker to initiate? Scenario 2: Able to tolerate target doses of one and less than target doses of the other therapeutic agent?

Consider metoprolol succinate for patients who are hypotensive on carvedilol, cannot tolerate much lower blood pressures, or patients with atrial fibrillation, COPD/asthma Optimal SNS modulation with target doses of beta blocker appears to have the best effect on HFrEF outcomes (cardiovascular mortality, pump failure mortality, and sudden cardiac death).

Early Versus Late Stages of Chronic Heart Failure

Br J Cardiol 2005;12:448–454.

• 20 % relative risk

reduction in the primary outcome

• 4.7% absolute risk

reduction in the primary outcome

• NNT: 21 over 27

months

N Engl J Med. 2014;371:993-1004

primary endpoint : death from cardiovascular causes and hospitalization for heart failure

Sacubitril/Valsartan

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

For patients stable on ACEI/ARB, NYHA class II- III Switch

ARNI

Sacubitril/Valsartan: Place in Therapy

HFrEF Stage C Treatment ACEI/ARBs and beta blockers with diuretic as needed

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

Yancy et al. JACC VOL. 71:2 ,2018

Prior to initiation:

• 36 hours wash out period with

ACEI

• Adequate blood pressure
• eGFR ≥ 30 ml/min/1.73m2

Starting dose based on prior dose of ACEI/ARB:

• 24/26 mg or 49/51 mg twice daily
• Target dose: 97/103 mg twice daily
• In 2-4 weeks, assess tolerability
• Increase dose to target
• Monitor: blood pressure,

electrolytes, and renal function both after initiation and during titration

ARNI

Sacubitril/Valsartan: Initiation and Titration

Yancy et al. JACC VOL. 71:2 ,2018

Barriers to titration

• Symptomatic hypotension
• Electrolyte/renal

instability, or angioedema

• Cost

Monitoring

• Hypotension
• Hyperkalemia
• Cough
• Renal function
• Monitor NT-proBNP, not

BNP

LCZ696 (n=4187) Enalapril (n=4212) P Value Prospectively identified adverse events Symptomatic hypotension 588 388 < 0.001 Serum potassium > 6.0 mmol/l 181 236 0.007 Serum creatinine ≥ 2.5 mg/dl 139 188 0.007 Cough 474 601 < 0.001 Discontinuation for adverse event 449 516 0.02 Discontinuation for hypotension 36 29 NS Discontinuation for hyperkalemia 11 15 NS Discontinuation for renal impairment 29 59 0.001 Angioedema (adjudicated) Medications, no hospitalization 16 9 NS Hospitalized; no airway compromise 3 1 NS Airway compromise

• Adverse Events

N Engl J Med. 2014;371:993-1004

Sacubitril/Valsartan Dosing

Starting dose Maintenance Dose Comments ACEI/ARB Naive 24/26 mg bid 97/103 mg bid Dose is doubled every 2 to 4 weeks Previously on ACEI/ARB Total daily dose <10 mg⃰ Total daily dose >10 mg Total daily dose <160 mg£ Total daily dose >160 mg 24/26 mg bid 49/51 mg bid 24/26 mg bid 49/51 mg bid 97/103 mg bid Allow 36 hour washout between ACEI and ARNI Dose is doubled every 2 to 4 weeks Severe Renal Impairment (eGFR<30 ml/min) 24/26 mg bid 97/103 mg bid Dose is doubled every 2 to 4 weeks. No dose adjustment needed for mild- moderate renal impairement. Hepatic Impairment (Child- Pugh B classification) 24/26 mg bid 97/103 mg bid Dose is doubled every 2 to 4 weeks. Use in severe hepatic impairment not recommended

⃰ Lisinopril £Valsartan

Common Clinical Scenarios

Scenario 1: When to initiate ARNI? Scenario 2: Initiation of an ARNI de novo without prior exposure to ACEI or ARB Scenario 3: Is use of aldosterone antagonist mandatory prior to using ARNI?

In persistently symptomatic patients who tolerate an ACEI or ARB, switching to an ARNI “Accept the uncertainty about effectiveness and safety as well as potentially greater

• ut-of-pocket costs, de novo initiation of ARNI with close follow-up and serial

assessments(blood pressure, electrolytes, and renal function) might be considered” Not mandatory prior to changing a patient to ARNI.

HFrEF – Aldosterone Antagonists

Aldosterone Antagonist Doses

Generic Name Trade Name Initial Daily Dose Target Dose Mean Dose Achieved in Clinical Trials Eplerenone Inspra 25 mg daily 50 mg daily 42.6 mg/day Spironolactone Aldactone 12.5-25 mg daily 25 mg daily 26 mg/day JACC 2013;62:e147-239

NYHA class II-IV

• eGFR ≥ 30
• Men: SCr ≤ 2.5 mg/dL
• Women: SCr ≤ 2.0

mg/dL

• K < 5.0 mEq/dL

Add

Aldosterone Antagonist

HFrEF Stage C Treatment ACEI/ARBs and beta blockers with diuretic as needed

Aldosterone antagonist

Yancy et al. JACC VOL. 71:2 ,2018

Aldosterone antagonist

Select initial dose

• Titrate doses every 2 weeks

until maximum tolerated or target dose is achieved

• Monitoring: electrolytes

(especially potassium) and renal function in 2-3 days and 7 days after initiation/titration

• Then, check monthly for 3

months and every 3 months afterwards

Aldosterone Antagonist: Initiation and Titration

Barriers to titration

• Symptomatic hypotension
• Worsening renal function
• Hyperkalemia

Monitoring:

• Hypotension
• Hyperkalemia
• Renal function
• Gynecomastia (spironolactone)

Yancy et al. JACC VOL. 71:2 ,2018

Appropriate follow-up laboratory testing across all time periods occurred in 25.2% of patients with inpatient initiation compared with 2.8% of patients begun as an outpatient. Patients with chronic kidney disease had higher rates of both hyperkalemia and acute kidney failure in the early (1.3% and 2.7%, respectively) and extended (5.6% and 9.8%, respectively) post- initiation periods compared with those without chronic kidney disease.

Circ Cardiovasc Qual Outcomes. 2017;10:e002946

Spironolactone causes hyperkalemia in a dose-dependent fashion

Optimal dosing of MRA in HF is limited by hyperkalemia

The RALES Investigators. Am J Cardiol 1996, 78(8):902-7

Aldosterone Antagonists

Eplerenone Spironolactone eGFR (ml/min/1.73m2) ≥50 30 to 49 ≥50 30 to 49 Initial dose (only if K+ ≤ 5mEq/L) 25 mg once daily 25 mg once every other day 12.5 to 25 mg

• nce daily

12.5 mg once daily or every

• ther day

Maintenance dose (after 4 wk for K+ ≤ 5mEq/L) 50 mg once daily 25 mg once daily 25 mg once or twice daily 12.5 to 25 mg

• nce daily

JACC 2013;62:e147-239

Clinical Scenarios

• Scenario 1: When to initiate aldosterone

antagonists?

• Scenario 2: Is it mandatory to be on target
• r max tolerated doses of beta blockers

and ACEI/ARB prior to initiating aldosterone antagonists?

In patients who are already receiving beta blockers and ACEI/ARB/ARNI who do not have contraindications. In practice we would like to optimize beta blockers and ACEI/ARBs first. However, in patients with persistent hypokalemia, earlier addition of an aldosterone antagonists may be considered.

Hydralazine/Isosorbide Dinitrate

Dose Hydralazine Isosorbide Dinitrate Initial dose 25-50 mg 3-4 times daily 20-30mg 3 times daily Max dose 100 mg 3-4 times daily 40mg 3 times daily

JACC 2013;62:e147-239

Hydralazine/Isosorbide Dinitrate: Place in Therapy

For persistently symptomatic AA, NYHA class II-IV ADD ACEI/ARBs and beta blockers with diuretic as needed Hydralazine / Isosorbide dinitrate

HFrEF Stage C Treatment Yancy et al. JACC VOL. 71:2 ,2018

Hydralazine / Isosorbide dinitrate

Select an initial dose either as individual medications or fixed–dose combination Consider increasing dose every 2 weeks Monitor BP

Hydralazine/Isosorbide Dinitrate: Initiation and Titration

Yancy et al. JACC VOL. 71:2 ,2018

African Americans

Establish GDMT with ACEI/ARB, beta blocker, and an aldosterone antagonist, then switch to ARNI (akin to patients studied in PARADIGM); if stable, follow with HYD/ISDN if patient has persistent class III to IV symptoms with careful blood pressure monitoring. Establish GDMT with ACEI/ARB, beta blocker, and an aldosterone antagonist and then proceed with HYD/ISDN if persistent class III to IV symptoms (akin to patients studied in A-HeFT) if stable, follow with ARNI substitution for ACEI/ARB with careful blood pressure monitoring.

OR

JACC 2013;62:e147-239

Ivabradine Doses for HFrEF

Population Initial Dose Max dose Max tolerated beta-blocker dose with persistent resting HR ≥ 70 5 mg BID Titrate to HR 50-60 bpm Max dose 7.5mg BID History of conduction defects 2.5 mg BID Age ≥ 75 years 2.5 mg BID J Am Coll Cardiol. 2018;71(2):201-230.

For patients with resting HR>70 bpm, on maximally tolerated beta blocker in sinus rhythm, NYHA Class II-III Add Ivabradine

Ivabradine: Place in Therapy

HFrEF Stage C Treatment ACEI/ARBs and beta blockers with diuretic as needed Yancy et al. JACC VOL. 71:2 ,2018

Ivabradine Monitoring

• Resting heart rate decreases persistently below

50 bpm or if symptoms of bradycardia occur

• If a patient develops persistent/continuous atrial

fibrillation (AF) during therapy

• Luminous phenomena (phosphenes – visual

color spots)

Wait! What About Digoxin?

• Reduced number of hospitalizations
• Improvements in

– Symptoms – Exercise tolerance – Quality of life

• Typical dose: 0.125 mg daily

Target Cp: 0.5-0.9 ng/mL

NO SURVIVAL BENEFIT!

Self-Care in Cardiovascular Disease

J Am Heart Assoc.2017;6:e006997

Patient Cases

Patient Case 1: Initiation of therapy

KS is a 67-year-old white man with a remote hx of heart failure. Recent ECHO on 3/5/2018 showed an ejection fraction of 25%. Today he reports trace edema and dyspnea with less than normal activity. Today’s vitals + labs: BP 132/77 mm Hg HR 80 bpm SCr 0.9 mg/dL BUN 19 mg/dL K 3.8 mEq/L Other labs wnl Current Medications: Aspirin 81mg Atorvastatin 40mg Amlodipine 5mg daily Chlorthalidone 12.5 mg daily Questions for Discussion:

• 1. How would you

stage/classify patient’s heart failure?

• 2. Assess patient’s current

therapy for heart failure KS’s physician plans to discontinue amlodipine and chlorthalidone. She also asks for a recommendation on starting GDMT. What would you recommend? HFrEF Stage C NYHA Class III

ACSAP 2018

Patient Case 1

• A. Initiate lisinopril 5mg daily
• B. Initiate lisinopril 20mg daily

C.Initiate carvedilol 3.125mg BID D.Initiate lisinopril 5mg daily and carvedilol 3.125mg twice daily

Appropriate option; Pt’s HR is 80 bpm Appropriate but aggressive; typically not started at such a high dose Appropriate option Appropriate option to initiate both simultaneously at low doses. However, patient has to have adequate BP and HR with close monitoring.

ACSAP 2018

Patient Case 1 (cont.)

At his 6-month visit, KS is taking lisinopril 20mg daily and carvedilol 25mg twice daily. He is also taking furosemide 20mg three times weekly as needed based on daily weight. Today’s vitals + labs: BP 119/70 mm Hg HR 70 bpm SCr 1.0 mg/dL BUN 14 mg/dL K 4.0 mEq/L Current Medications: Aspirin 81mg Atorvastatin 40mg Lisinopril 20mg daily Carvedilol 25mg BID Furosemide 20mg TIW PRN KS is clinically stable, but states that he “gets winded a little easier than he used to be with normal activities.” What would you recommend adding to K.S’s HF regimen?

ACSAP 2018

Patient Case 1 (cont.)

• A. Spironolactone 12.5mg daily
• B. Sacubitril/valsartan 24mg/26mg BID
• C. Valsartan 40mg BID
• D. Digoxin 0.125mg daily

ACEI and ARB combination is not appropriate Appropriate as an add-on (third life-prolonging agent) No mortality benefits May consider (with a 36-hr washout). However, his symptoms are stable and he is not requiring more diuretic doses.

ACSAP 2018

Patient Case 2: Exacerbation

KJ is a 60 year old woman with HFrEF who is referred to the HF clinic for

• evaluation. Her EF is 30% and prior work-up was negative for coronary disease.

Current HF medications – Sacubitril/valsartan 49/51 mg BID – Metoprolol succinate 100mg daily (increased 2 weeks ago from 50mg daily) – Spironolactone 12.5 mg daily – Furosemide 40 mg daily KJ currently complains of worsening fatigue, dyspnea, and weight gain (5lbs) BP: 100/60 mm Hg HR: 95 BPM 1+ pitting edema to her shin + JVD lungs are clear SCr 1.2 mg/dL (stable) K is 5.1 mEq/L Which one of the following, in addition to increasing furosemide to 40mg BID, is best to recommend for KJ?

ACSAP 2018

Patient Case 2

• A. Decrease metoprolol to 50mg daily
• B. No other changes to current therapy
• C. Increase sacubitril/valsartan to 97/103 mg BID
• D. Increase metoprolol to 150 mg daily
• No. Denies symptomatic hypotension/bradycardia.

Not now. BP 100/60 mm Hg and K is 5.1.

• No. Avoid titration during an exacerbation.
• Yes. Pt in exacerbation and has low BP

ACSAP 2018

Patient Case 3: ARNI

PK is a 55-year-old white woman with HFrEF, stage C, NYHA class III with a history of angioedema with lisinopril. Today’s vitals + labs: BP 120/70 mm Hg HR 75 bpm SCr 1.2 mg/dL K 5.0 mEq/L Current Medications: Carvedilol 25mg BID Furosemide 40mg BID Spironolacone 12.5mg daily Losartan 100mg daily Which of the following is best to recommend for this patient?

ACSAP 2018

Patient Case 3

• A. Start sacubitril/valsartan 49/51 mg BID 36 hours after the last

dose of losartan

• B. Start sacubitril/valsartan 97/103 mg at the next dosing

interval

• C. Do not start sacubitril/valsartan because of K 5.0 mEq/L
• D. Do not start sacubitril/valsartan because of hx of angioedema

with ACE-i

Washout period of 36 hours is not required if pt is on an ARB The most common side effect is hypotension. Sacubitril/valsartan should not be initiated at full dose even if pt was on target or higher dose of ACEI or ARB The PARADIGM-HF trial only excluded patients if their K was >5.2 mEq/L PARADIGM-HF excluded patients with a history of angioedema

ACSAP 2018

Questions