The Beat Goes On: How to Assess Patients with Heart … · Discuss patient assessment tools that are appropriate for pharmacists to use when assessing patients with heart failure;

The Beat Goes On: How to Assess Patients with Heart Failure Robert Page, PharmD, MSPH and Lynne Sylvia, PharmD

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Target Audience: Pharmacists

ACPE#: 0202-0000-18-047-L01-P

Activity Type: Application-based


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DisclosuresLynne Sylvia, PharmD: None

Robert L Page, PharmD, MSPH: None

The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.


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Learning Objectives

1. Discuss patient assessment tools that are appropriate for pharmacists to use when assessing patients with heart failure;

2. Evaluate pharmacologic options for management of heart failure;

3. Apply evidence-based findings and recommendations regarding the risks and benefits of pharmacologic treatments for heart failure to patient cases.

4. Develop a care plan that encompasses evidence-based medicine and pharmacoeconomicconsiderations.

At the completion of this application-based activity, participants will be able to:


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1. Assessment Question

What is the first step in initiating pharmacy-based care for a patient with heart failure?

A. Perform medication reconciliation B. Assess current therapies for compliance with guideline-

directed therapiesC. Establish a relationship with the patient D. Assess medication adherence with current therapies


Based on the signs/symptoms and physical findings, which of the following patients would be considered a “cold and wet”?

A. 65 year old with Scr 2.0 mg/dl, + PND.B. 55 year old with warm extremities, +3 pitting edema.C. 80 year old with a narrow pulse pressure, -JVD.D. 75 year old with normal LFTs, extreme fatigue.

3. Assessment QuestionWhich of the following has been associated with a falsely elevated serum BNP level?A. ObesityB. PericarditisC. Pulmonary embolismD. Flash pulmonary edema


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4. Assessment QuestionWhich of the following statements is correct regarding treatment of hyperkalemia in a patient with HF on guideline-directed therapies?

A. Treatment is only indicated when K exceeds 5.5 mEq/L B. Modifiable factors include diet and drugs such as NSAIDs,

trimethoprim, and some herbal preparations C. Aldosterone antagonist dosing should be reduced by 50%D. All guideline-directed therapies must be discontinued

temporarily until hyperkalemia is resolved

Warm-Up Activity ---- Meet Vincent Vincent is a 51 year old Caucasian man recently diagnosed with HFrEF(LVEF 20 %) with NYHA Class 3 symptoms

• Referred to the Advanced HF Clinic; this is his first visit • PMH: nonischemic CMP 2 months ago (possible etiology = familial),

HTN, DM Type 2 • Feels ‘better than before his diagnosis’ but still fatigued with SOB • Medications = carvedilol 3.125 mg po BID, furosemide 40 mg po BID,

lisinopril 5 mg po once daily, spironolactone 25 mg po once daily, glimepiride 2 mg po once daily

• PE: BP 100/60, 95/55 on repeat; HR 97 and 104, RRR, JVP 14 cm at 90°, no pedal edema, + abdominal bloating, weight = 170 lb (up from 162), A + O x 3

• ROS: DOE, 2 pillow orthopnea, denies syncope or dizziness • Labs: pending

Vincent: What Does His Story Tell You?

Your observations:

First visit

Newly diagnosed HF

On core guideline directed therapies but still symptomatic

Weight is up by at least 5 pounds

Low BP and tachycardic

RRR

Has diabetes

What Don’t You Know about Vincent…

Labs - lytes, renal function, albumin, A1C

What does he do for a living? (can influence medication adherence)

Living situation? Family support?

Prescription insurance and co-pays? Medication adherence?

OTC use – is he aware of avoidance of particular medications?

Diet – sodium and volume intake?

Has he ever been educated about HF and its management?

Does he know his dry weight? Does he own a scale?

Where do You Begin to Provide Care?

What is the first step in initiating pharmacy-based care for Vincent?

A. Perform medication reconciliation B. Assess current therapies for compliance with guideline-

directed therapiesC. Establish a relationship with the patient D. Assess medication adherence with current therapies

HF Consultation: Where do you Begin?

Medication Reconciliation• Collect • Compare • Correct • Communicate

Allergy/Intolerances

Guideline- Directed Therapies• Know the recent guidelines and

hallmark RCTs• Assess appropriateness of therapy • Document, document, document

Education for Self-Care

• Symptom tracker• Medications• Diet and Fluid Intake• Provider Access

Transition of Care• Follow-up Phone Call • Home visit • Telemonitoring

The Four Pillars Plus 1:

Establish a Relationship

Additional Essential Roles: HF Pharmacists Ensuring Drug Access

Prior authorizations, patient assistance programs

Education on Complex Therapies Self-administration of enoxaparin as outpatient, insulin regimens, conversion from ACEIs or ARBs to

sacubitril/valsartan, IV iron

Pill Box fills or blister packs

Anticoagulation Monitoring for patients with mechanical assist devices (LVADs)

IV infusion therapies: home milrinone or dobutamine infusion, IV diuretic clinics

Heart transplant patients: evaluations, drug level monitoring, education

Protocol development for Complex Therapies

To be effective…

You may need to shore up your Toolbox!

HF Guidelines and Hallmark RCTs

Patient Assessment Tools

Customized Educational Materials

Team-based Attitude

Empathy and Compassion

Listening skills

Time-Efficient Strategies

Our Ultimate Goal for this Session

Using a series of patient scenarios…

Illustrate how you provide optimal integrated care to the patient with chronic heart failure through

Outreach and relationship building, Knowledge of guideline-directed therapies, Effective use of available tools including physical assessment, Effective communication.

Case 1

C.J. is a 75-year-old man (height 5′8′′, weight 72 kg) with ischemic cardiomyopathy (EF 30%) presenting to the emergency room with worsening dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea.

PMH: CAD, hyperlipidemia, hypertension, and CKD.

Vital signs: BP 117/68 mm Hg, HR 75 beats/minute, RR 23 breaths/minute, and oxygen saturation 94% on 4 L nasal cannula.

Case 1

Physical Exam: JVD to his ear lobe, rales bilaterally, and 3+ bilateral lower extremity edema to his knees, but only mild abdominal edema. He admits a 10-lb weight gain in the past 2 weeks after running out of his home drugs.

Pertinent laboratory values: sodium 136 mmol/L, potassium 4.8 mmol/L, BUN 59 mg/dL, SCr 1.9 mg/dL (baseline 1.7 mg/dL), N-terminal proBNP 4530 pg/mL (baseline 1800 pg/ml) , AST 20 U/L, ALT 10 U/L.

Review of Function Class and StagesACCF/AHA Stages of HF NYHA Functional Classification

A At high risk for HF but without structural heart disease or symptoms of HF

None

B Structural heart disease but without signs or symptoms of HF

I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.

C Structural heart disease with prior or current symptoms of HF

I

II

III

IV

No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.

Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF.

Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF.

Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.

D Refractory HF requiring specialized interventions

IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.

Circulation. 2013; 128:e240-e327.

Used with Permission. Yancy et al. JACC. 2017. Published ahead of print. Available at: http://www.onlinejacc.org/content/early/2017/12/12/j.jacc.2017.11.025. Accessed January 13 2018

Testing and Medication Titration Following Diagnosis of HFrEF

Essential Components of the Heart Failure Examination

General Appearance

Vital Signs in recumbent and upright positions Heart Rate

Blood Pressure

Jugular Venous Pressure/Hepatojugular Reflux

Auscultation of the chest, percussion as needed

Examination for peripheral edema and perfusion:

As needed or observed: Skin appearance and temperature (to touch) of hands and feet

Pulse character, contour, and duration (carotid and/or femoral sites)

Number of pillows (measure of orthopnea)

Hemodynamic Correlates of Major Physical Findings Jugular Vein Jugular venous pressure (in the absence of atrioventricular valvular stenosis): approximates right

ventricular diastolic pressure and can provide a clue to the state of left ventricular diastolic pressure

Hepatojugular (abdominojugular) reflux of ≥3 cm when jugular venous pressure is <10 cm: marginal or mild volume overload Blood Pressure

Epomedicine. Jugular Venous Pressure. Available at:http://epomedicine.com/clinical-medicine/clinical-examination-jugular-venous-pulse-pressure-jvp/. Accessed December 10, 2017. Rated Medicine. Jugular Venous Pressure. Available at: https://ratedmedicine.wordpress.com/jugular-venous-pressure/. Accessed December 10, 2017.

Hemodynamic Correlates of Major Physical Findings

https://www.youtube.com/watch?v=qVavuwgMf54


Precordium Left parasternal lift (right ventricular heave): right ventricular pressure and/or volume overload

Hypokinetic (weakened) ventricular impulse: decreased ventricular contractility, often a reduced ejection fraction

Wide, sustained left ventricular impulse (>50% of systole): increased left ventricular mass

Laterally displaced left ventricular impulse: ventricular chamber enlargement

Reduced intensity of S1 with unchanged PR interval: elevation of left ventricular end diastolic pressure

Increased intensity of P2: pulmonary arterial hypertension

S4 gallop: increased ventricular stiffness in diastole (reduced ventricular compliance)

S3 gallop in adults (without severe atrioventricular valve regurgitation or pregnancy): increased ventricular diastolic pressure and filling

Systolic murmur along lower left sternal border, which increases on inspiration: tricuspid regurgitation


Extremities Dependent edema: often volume overload

Cool, moist hands and feet: low cardiac output, increased sympathetic tone, and elevated SVR

Assessing Pitting Edema

Trace Minimal depression noted when pressure applied

+1 Application of pressure creates a depression of 2 mm; no visible distortion; rapid return of skin to position

+2 Application of pressure creates a depression of 4 mm in depth that disappears in about 10-15 seconds

+3 Application of pressure creates a depression of approximately 6mm in depth that lasts 1-2 minutes; area may appear swollen

+4 Application of pressure creates a depression up to 8 mm in depth that persists for 2-3 minutes; area is grossly edematous

Hemodynamic Correlates of Major Physical Findings Extremities Congestion

LowPerfusion

No

No Yes

Yes

Warm & Dry Warm & Wet

Cold & WetCold & Dry

PCWP 18

CI 2.2

Signs/Symptoms ofCongestion:Orthopnea/PNDJV DistentionHepatomegalyEdemaRalesAbd-Jugular Reflux

Signs/Symptoms of Low Perfusion:Narrow pulse pressure Cool Extremities Sleepy/obtunded Hypotension Low serum sodium Renal/Hepatic dysfunction


Based on the signs/symptoms and physical findings, which of the following patients would be considered a “cold and wet”?

A. 65 year old with Scr 2.0 mg/dl, + PND.B. 55 year old with warm extremities, +3 pitting edema.C. 80 year old with a narrow pulse pressure, -JVD.D. 75 year old with normal LFTs, extreme fatigue.

Roles of BNP and NT-proBNP:

Correlate with LVED wall stress

Support diagnosis

Predict mortality, HF events

Guide therapy and make adjustments

Does NOT improve outcomes (GUIDE-IT Trial)

Circulation. 2017. 135(22):e1054-e1091

Other Important Laboratory Findings: Natriuretic Peptides

Cutoff Valuepg/ml

Sensitivity%

Specificity%

PPV%

NPV%

To Exclude Acute Heart Failure

BNP <30-50 97 62 71 96

NT-proBNP

<300 99 68 62 99

To Identify Acute Heart Failure (Single Cut Off Strategy)

BNP <100 90 76 79 89

NT-proBNP

<900 90 85 76 94

Cardiac Biomarkers. Expert Analysis. American College of Cardiology. 2015. Available at: http://www.acc.org/latest-in-Cardiology/%20articles/%202015/%2002/09/13/00/cardiac-biomarkers-and-heart-failure. Accessed January 13, 2018.


Cutoff Valuepg/ml

Sensitivity%

Specificity%

PPV%

NPV%

Multiple Cut Point Strategy for Acute Heart Failure

BNP, gray Zone

<100, to exclude 90 73 75 90

100-400 gray zone

? ? ? ?

>400 ,to rule in 63 91 86 74

NT-ProBNP

<300, to exclude 99 62 55 99

<450 for age <50 years, to rule in

97 93 76 99

<900 for age 50-75 years, to rule in

90 82 82 88

<1800 for age >75 years, to rule in

85 73 92 55

Cardiac Biomarkers. Expert Analysis. American College of Cardiology. 2015. Available at: http://www.acc.org/latest-in-Cardiology/%20articles/%202015/%2002/09/13/00/cardiac-biomarkers-and-heart-failure. Accessed January 13, 2018.


Circulation. 2017. 135(22):e1054-e1091

Higher Natriuretic Peptide Levels Than Expected

Lower Natriuretic Peptides Than Expected

• Increasing age*• ACS*• Renal insufficiency• RV dysfunction• AF• Pulmonary hypertension*• Pulmonary embolism*• Anemia/high out states*• Sepsis• Mitral regurgitation*

• Obesity• Flash pulmonary edema• Pericarditis/tamponade• Genetic polymorphisms• End-stage cardiomyopathy

ACS=Acute coronary syndrome, AF=Atrial fibrillation, RV = Right ventricular.*Delineates likely elevation from ventricular stretch

3. Assessment QuestionWhich of the following has been associated with a falsely elevated serum BNP level?A. ObesityB. PericarditisC. Pulmonary embolismD. Flash pulmonary edema

Case 1: Think Pair Share1. On physical exam, what physical findings suggest HF

exacerbation?

2. How would you “classify” this patients HF?

3. How would you interpret this patients BNP?

Case 1: Think Pair Share

Meds: atorvastatin 40 mg/day, aspirin 81 mg/day, enalapril 10 mg twice daily, carvedilol 12.5 mg twice daily, digoxin 125 mcg/day, and furosemide 40 mg twice daily.

1. After evaluating this patients sign/symptoms, what should be done with this patient’s diuretic regimen? What dose would your recommend?

2. What should be done with this patients ACE-inhibitor?

3. What about the beta-blocker?

Used with Permission. Yancy et al. JACC. 2017. Published ahead of print. Available at: http://www.onlinejacc.org/content/early/2017/12/12/j.jacc.2017.11.025. Accessed January 13 2018

Drug Titration of GDMT for HFrEF

New Engl J Med. 2011; 364: 797-805.

DOSE-AHF:Diuretic Titration in Acute Heart Failure

Acute Heart Failure (1 symptom AND 1 sign)<24 hours after admission

2x2 factorial randomization

Low Dose (1 x oral)Q12 IV bolus

48 hours

1) Change to oral diuretics2) continue current strategy3) 50% increase in dose

Co-primary endpoints

High Dose (2.5 x oral)Q12 IV bolus

Low Dose (1 x oral)Continuous infusion

High Dose (2.5 x oral)Continuous infusion

72 hours

Clinical endpoints

60 days

Primary Endpoint: Change in Visual Analogue Scale

New Engl J Med. 2011; 364: 797-805.

0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60 70

Visu

al A

nalo

g Sc

ale

Hours

VAS assessed at 6, 12, 24, 48, 72 hours

Secondary Endpoints:Q12 vs. ContinuousQ12 Continuous P value

Dyspnea VAS AUC at 72 hrs 4456 4699 0.36

% free from congestion at 72 hrs 14% 15% 0.78

Change in weight at 72 hrs -6.8 lbs -8.1 lbs 0.20

Net volume loss at 72 hrs 4237 mL 4249 mL 0.89

Change in NTproBNP at 72 hrs (pg/mL) -1326 -1773 0.44

% treatment failure 38% 39% 0.88

% with Cr increase > 0.3 mg/dL within 72 hrs

17% 19% 0.64

Length of stay, days (median) 5 5 0.97

New Engl J Med. 2011; 364: 797-805.

Secondary Endpoints: Low vs. High Intensification

Low High P value

Dyspnea VAS AUC at 72 hours 4478 4668 0.041

% free from congestion at 72 hrs 11% 18% 0.091

Change in weight at 72 hrs -6.1 lbs -8.7 lbs 0.011

Net volume loss at 72 hrs 3575 mL 4899 mL 0.001

Change in NTproBNP at 72 hrs (pg/mL) -1194 -1882 0.06

% Treatment failure 37% 40% 0.56

% with Cr increase > 0.3 mg/dLwithin 72 hrs

14% 23% 0.041

Length of stay, days (median) 6 5 0.55

New Engl J Med. 2011; 364: 797-805.

Proportion with Worsening Renal Function*:Low vs. High

0%

5%

10%

15%

20%

25%

0 1 2 3 4 7 60

Low High

% w

ith Δ

Cr >

0.3

mg/

dL

Days

P > 0.05 for all timepoints

*Based on local lab creatinine valuesNew Engl J Med. 2011; 364: 797-805.

0

0.1

0.2

0.3

0.4

0.5

0.6

0 10 20 30 40 50 60

Prop

ortio

n w

ith D

eath

, Reh

osp,

or E

D Vi

sit

Days

Continuous Q12

Death, Rehospitalization, or ED VisitHR for Continuous vs. Q12 = 1.19

95% CI 0.86, 1.66, p = 0.30HR for High vs. Low = 0.8395% CI 0.60, 1.16, p = 0.28

0

0.1

0.2

0.3

0.4

0.5

0.6

0 10 20 30 40 50 60

Pro

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with

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New Engl J Med. 2011; 364: 797-805.

Case 2

PH is a 75 y/o, 70-kg man with a 2 year history of HFrEF (EF 25%), NYHA class III, and a history of one hospitalization in the past 6 months presents for a regular f/u visit.

Chief complaint of extreme fatigue and external dyspnea

Current meds: carvedilol, furosemide, potassium chloride, losartan, aspirin, spironolactone, citalopram, acetaminophen, zolpidem, and vit D

Case 2 PMH: STEMI ( 2 years ago), HTN, DM (diet controlled), HFrEF

(LVEF: 40%, NYHA class III), Hyperlipidemia, and depression

Routine labs : SCr 1.4 mg/dL, calculated CrCl = 45 mL/min

K+ 4.5 mmol/L

HgA1c 7.2 mg/dL

Hb 10.5 g/dL

Low MCV

Ferritin 150 ng/mL

Tsat 14%

Iron-Deficiency : Epidemiology in HF

Iron deficiency occurs in > 1/3 of patients with HF Common cause of anemia More likely to occur in women vs men Prevalence increases with HF disease severity

2 types of iron deficiency Absolute: depleted iron stores, with intact iron homoeostasis mechanisms

Common causes: low-dietary intake, impaired GI absorption, GI blood loss, menorrhagia

Functional: normal or high iron body stores, but iron is trapped inside cells of the reticuloendothelial system and is unavailable for cellular metabolism

JACC. 2008;52:818-27; Circulation. 2006;113:2454-61. Heart Failure Clin. 2010;6:279-88; JACC. 2006;48:2485-9;Eur Heart J. 2010;31:1872-80; Eur Heart J. 2013; 34(11): 816–829.

Iron-Deficiency : Pathophysiology in HF

Renal dysfunction, neurohormonal and proinflammatory cytokine activation

Inappropriate erythropoietin production and defective iron utilization, leading to ↓ intestinal iron absorption and accumulation within the reticuloendothelial stores

Hemodynamic responses to hypoxia: vasodilation-mediated high-output state with neurohormonalactivation—to increase oxygen transport

Heart Fail Clin. 2010;6(3):279-88; Eur Heart J. 2013; 34(11): 816–829.

Mortality with Iron-Deficiency in HF

Eur Heart J. 2013;34(11):816-29.

Iron-Deficiency Anemia: Symptoms Fatigue Exercise intolerance Exertional dyspnea Chest painWeaknessHeadache IrritabilityVertigo

Iron-Deficiency Anemia: DiagnosisCBC

Low Hemoglobin (Hb) <13 g/dL (men) or <12 g/dL (women)May have low mean corpuscular volume (MCV) or mean corpuscular

hemoglobin (MCH)

Serum ferritinMay be low (<100 ng/mL = absolute iron deficiency)May be normal (100-300 ng/mL = functional iron deficiency)

Iron binding panel = transferrin, % transferrin saturation (Tsat), total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) Tsat <20% accompanied by normal ferritin = functional iron deficiency

May also want to consider ordering serum vitamin B12

. JACC. 2006;48:2485-9.; Eur Heart J. 2013; 14; 34(11): 816–82.

Iron Absorption Iron is absorbed in the upper GI tractDuodenum is the site of maximal absorption

Mucosal cells are responsible for iron absorption, and older adults with certain conditions may ↓ absorptionCeliac disease, atrophic gastritis, H. pylori infection, and

previous bariatric surgery

Clinical Investigation of Iron Replacement TRIAL INCLUSION CRITERIA

FERRIC-HF 2008 Ferritin <100 ng/mL or 100-300ng/mL w/TSat <20%; Hb ≤ 14.5 g/dL; NYHA II-III; EF ≤45%

J NEPHROL 2008 Hb <11 g/dL, NYHA III-IV

FAIR-HF 2009 Ferritin <100 ng/mL or 101-299ng/mL w/ TSat <20%; Hb 9.5-13.5g/dLNYHA II-III, HFrEF ≤40-45%

IRON-HF 2013 Ferritin <500 ng/mL and TSat <20%; Hb 9-12 g/dL; Hb 9-15 g/dL; NYHA II-III, III), LVEF<40%

CONFIRM-HF 2015 Ferritin <100 ng/mL or 100-300ng/mL w/ TSat <20%; Hb <15 g/dL; Symptomatic HFrEF ≤45%, NYHA II-III, and high BNP

IRONOUT-HF 2017 Ferritin <100 ng/mL or 101-299ng/mL w/ TSat <20%; NYHA II-III, HFrEF ≤40%

EFFECT-HFAbstract

Ferritin <100 ng/mL or 100-300ng/mL w/TSat <20%; Hb <15 g/dL; NYHA II-III, HFrEF ≤45%

J Am Coll Cardiol 2006;48:1225-1227; J Am Coll Cardiol 2008;51:103-112; J Nephrol 2008;21:236-242; N Engl J Med 2009; 361:2436-2448; Int J Cardiol 2013;168:3439-3442; Eur Heart J. 2015; 36:657-68.; 7. JAMA 2017;317(19):1958-1966

Clinical Investigation of Iron Replacement TRIAL N DRUG REGIMEN

FERRIC-HF 2008 35 IV IS 200 mg/wk until ferritin >500, then Qmo; or no treatment

J NEPHROL 2008 32 IV IS 100mg TIW x 3wks, then weekly x 23wks

FAIR-HF4 2009 459 IV FCM 200mg weekly, then Qmo starting at wk 8 or 12; or placeboUsed Ganzoni formula9

IRON-HF5 2013 23 IV IS 200 mg/wk x 5 wks or FeSO4 200mg TID X 8wks or placebo

CONFIRM-HF6 2015 304 IV FCM 500-1000 mg based on weight/Hb at weeks 0, 6; 500mg at wks12, 24, and 36 depending upon Tsat and ferritin or placebo

IRONOUT-HF7 2017 225 Oral iron polysaccharide 150mg BID or placebo

EFFECT-HF8 Abstract 174 IV FCM at weeks 0, 6 and 12; or placebo ± oral iron

IV IS = IV Iron sucrose = Venofer®; IV FCM = Ferric carboxymaltose = Injectafer®

J Am Coll Cardiol 2006;48:1225-1227; J Am Coll Cardiol 2008;51:103-112; 3; J Nephrol 2008;21:236-242; N Engl J Med 2009; 361:2436-2448; 5.Int J Cardiol 2013;168:3439-3442; Eur Heart J.2015; 36:657-68; JAMA 2017;317(19):1958-1966.

Clinical Investigation of Iron Replacement TRIAL OUTCOMES

FERRIC-HF 2008• 16-wk f/u• Mean dose: 1433mg

• ↑ Hb (by 0.1), ↑ ferritin (by 273), ↑ Tsat (by 11)• Improved exercise capacity, improved symptoms; effects ↑ if anemic

J NEPHROL 2008• 26 wk f/u• Mean dose: 3200mg

• ↑ Hb (by 3), ↑ ferritin (by 40), ↑ Tsat (by 13-18)• Improved functional class from III to II and improved cardiac defects and

LVEF in class III patients; less robust response in class IV patients

FAIR-HF 2009• 24 wk f/u• Median dose ≈ 2000

mg

• Significant improvement in patient global assessment (50% much/moderately improved vs 28%, OR 2.51)

• Significant improvement in functional class (47% class I or II vs 30% at wk-24, OR 2.40) and significant improvement in 6MW test and QOL

• Results similar in patients with anemia/no anemia• No difference in death or adverse events

J Am Coll Cardiol. 2006;48:1225-1227; J Am Coll Cardiol. 2008;51:103-112; 3. J Nephrol. 2008;21:236-242; N Engl J Med. 2009; 361:2436-2448

Clinical Investigation of Iron Replacement

TRIAL OUTCOMES

IRON-HF 2013• 12 wk f/u• Mean dose: 1000 mg

• No diff in Hb between oral/IV iron, ↑ ferritin in oral & IV iron (only significant w/oral iron), Tsat ↑ significantly in IV compared to placebo

• VO2max increased in IV iron group but not oral iron group

CONFIRM-HF 2015• 52 wk f/u• Mean dose: 1500 mg

• Significant improvement in 6MW, NYHA class, PGA, QOL & fatigue starting at week 24—consistent amongst all subgroups through wk52

• Significant reduction in hospitalization for worsening HF (HR 0.39) and trend for reduction in hosp due to any CV reason (HR 0.63)

• No difference in deaths or adverse event

IRONOUT-HF 2017• 16 wk f/u• Oral 150mg BID

• Significant ↑ Tsat (2 pts); Nonsig ↑ ferritin (18 pts)• No difference in change in VO2 max• No difference in 6MW distance, NT-proBNP levels or KCCQ QOL score

Int J Cardiol 2013;168:3439-3442; Eur Heart J.2015; 36:657-68.; JAMA 2017;317(19):1958-1966

2017 AHA/ACC Guideline Recommendations

Routine evaluation of HF patients should include evaluation for anemia

In patients with HF and anemia, erythropoietin-stimulating agents should not be used to improve morbidity/mortality

75 y/o, 70-kg man with a 2 year history of HFrEF (EF 25%), NYHA class III, and a history of one hospitalization in the past 6 months presents for a regular f/u visit

Current meds: carvedilol, furosemide, potassium chloride, losartan, aspirin, spironolactone, citalopram, acetaminophen, zolpidem, and vit D

Routine labs are checkedSCr 1.4 mg/dL, calculated CrCl = 45 mL/min

K+ 4.5 mmol/L

Hb 10.5 g/dL

Low MCV

Ferritin 150 ng/mL

Tsat 14%

• Should this patient be treated with oral iron?

• Should this patient be treated with IV iron?

Case 2-Questions for Discussion

IV Ferric Carboxymaltose

FDA approved for iron-deficiency anemia in adults with CKD or those who have intolerance to oral iron or have had an unsatisfactory response to oral ironDose: FDA approved 750mg weekly X 2 doses if >50 kg? re-dosing like in clinical studies to maintain ferritin/Tsat IV infusion over at least 15 min or slow IV push over at least 7.5 min

Some clinical trials gave over 1 minMonitor for hypersensitivity and increases in BP for 30 min after administrationAdverse effects: nausea (7%, all others <5%), HTN, HA, dizziness, vomitingCost: ≈$1200 per 750 mg/15 mL single-use vial Insurance coverage: likely covered by Medicare Part B and commercial plans, possibly

with PA, Medicaid may/may not cover

Return to the Beginning – Vincent First visit:

BP 95-110/55-60, NSR with HR 100, JVD, abdominal edema, DOE, 2 pillow orthopnea

Carvedilol 3.125 mg po BID, lisinopril 5 mg daily, furosemide 40 mg po BID, spironolactone 12.5 mg po once daily

Labs: AIC 6%, Na 137, K 4.6, BUN/Scr 16/1.43, BNP 937, H/H 14.4/42

Changed furosemide to torsemide and reduced lisinoprilto 2.5 mg po daily

First Visit with Pharmacist:

Establish a relationship

Medication Reconciliation

Insurance Assessment/Drug Access/Adherence

Education:

Action Zones

Weight management/scale

Time of diuretic dosing

Call back in 48 hours to reinforce plan

Action Zones

www.RiseAboveHF.org

If weight is increased by 3 lbs in a day or 5 lbs, in a week, take an extra dose of torsemide

One year later… Vincent CC - “I have more energy. According to my FitBit, I am walking at least 5,000 steps a day. I only get short of breath when I climb stairs - I can’t do stairs well”

Current Medications: carvedilol 6.25 mg po BID, sacubitril-valsartan 49/51 mg po BID, spironolactone 12.5 mg po once daily, torsemide 20 mg po BID (reduced dose)

Vital signs: BP 110/65 mm Hg, HR 65, weight 160 lbs (dry weight) PE: - JVD, RRR, - peripheral edema, - abdominal edema ROS: reports improved appetite and activity level, DOE only with stairs, - PND, in Green Zone most days, takes an extra dose of torsemide “once every 2 weeks”

Labs: K 5.6, BUN/Scr 32/1.4

History: K 5.0 to 5.4 after 1 month on sacubitril/valsartan plus spironolactoneReduced spironolactone to 12.5 mg (from 25 mg) 1 month ago Educated on low potassium diet

Hyperkalemia in HF – The Evidence

Our patient: K 5.6 mEq/L; Sustained Not controlled by diet alone Reduced diuretic requirement

“Serum K should be maintained below 5 mEq/L”“Potassium > 5.5 mEq/L should generally trigger dose reduction

or drug discontinuation” Yancy CW et al. Circulation 2013; 62(16): e147-239

Clinical Trials of ACEIs, ARBs and AAs in HF:

Mild hyperkalemia = > 5 but < 5.5 mEq/LModerate hyperkalemia = ≥ 5.5 but < 6 mEq/LSevere hyperkalemia = ≥ 6 mEq/L

‘Levels 5.5 mEq/L or greater are of concern and should prompt discontinuation of one or more offending drugs with short-term

follow-up to confirm a return to normal’ Desai AS. Current Heart Failure Reports 2009;6:272-280

Treatment of Chronic, Persistent Hyperkalemia Modifiable Factors:

Dietary considerations: Decrease high potassium foods (e.g., avocados, raisins, squash)

Remove non-HF medications that are contributory NSAIDs, trimethoprim, herbal agents

Reduce doses of guideline-directed therapies (ACEIs, ARBs and AAs)

Oral potassium binding resins and polymers

Premise of GI Resins and Polymers: • Normally, 90% of K removed via kidneys and 5-10% via colon into stool • In CKD, colonic secretion of K via BK channels increases as an adaptive phenomenon • Colonic secretion may be up-regulated 2 to 8 fold • Cationic exchange resins bind to potassium in the colon and facilitate K excretion in

stool

Cation Exchange Resins Sodium polystyrene sulfonate

(SPS; Kayexalate®) Patiromer

(Veltassa®)

Approval 1958 October 2015

Action • Exchanges sodium for K • Each 1 gram of SPS provides

100 mg Na (30 grams = 3000 mg Na)

• Co-formulated with sorbitol (20 grams)

• Exchanges calcium for K• Acts predominantly in the distal

colon where K [ ] is the highest• Minimal calcium absorption • Sorbitol content: 4 grams (8.4 g

dose)

Dose • 15 to 60 grams 1-4 times a day • 30-50 grams PR every 6 hours

• 8.4, 16.8 or 25.2 g packets orally/day with food

Warnings • Intestinal necrosis • Low magnesium and calcium• Binding to medications

• Worsening of GI motility • Hypomagnesemia• Binding to medications

Adverse Effects

• Edema, Hypokalemia, Constipation, Diarrhea

• Constipation (11%), Magnesium wasting (5.3%) , Hypokalemia (4.7%)

Cost per day

• $/dose x 2 to 3 doses/day • $$$/dose x 1 dose per day

The Evidence in HF Sodium polystyrene

sulfonate (SPS; Kayexalate®)

Patiromer(Veltassa®)

Study Data • Uncontrolled studies,retrospective cohorts (including14 patients on RAASi)

• Total < 150

• RCTs of patients with CKD, DM andHF with hx hyperK on ≥RAASi

• Total 654 (48% with HF on RAASi)

Duration of Study

• Up to 14.5 months (14 patients)• 1 - 280 days (32 patients)

• 12 weeks (HF)• 52 weeks (CKD, DM)

Onset • > 2 hours; maximal effect in > 6hours

• ~ 7 hours

Extent of potassium reduction

• - 0.14 mEq/L after 1 dose (15 g)• No change at 4, 8 and 12 hours

(30 g dose) • At 14.5 months, -1.8 mEq/L

(n=14 HF patients on RAASi)• After 7 days, mean -1.04 mEq/L

(95%CI -0.71 to -1.37 mEq/L)

• By 7 hours, -0.21 mEq/L (mean)• At week 4, -1.06 mEq/L ± 0.05

Meaney CJ et al. Pharmacotherapy 2017;37(4): 401-11

Patiromer in Heart Failure – The Evidence Study Inclusion Criteria Study Sample Intervention Results

PEARL-HF

N= 105

Pitt B et al. Eur Heart J 2011; 32(7): 820-828.

Baseline K 4.3 to 5.1And

HF with indication tostart spironolactone inaddition to EITHER 1)history of hyperK withinpast 6 months that ledto ACEI/ARB or AA d/c or2) CKD (crcl < 60mL/min) with continuedACEI/ARB

NYHA Classes II or III(87%); 41% had hxhyperK due toACEI/ARB/AA; 50% CKD;DM 30%

70% receiving an ACEI orARB plus a beta-blocker

Patiromer 15 grams BID(n=55) versus placebo(n=49); 4 week study

Introduction ofspironolactone 25mg/day; titrated to 50mg/day in 2 weeks if K ≤5.1

Mean difference in K -0.45mEq/L favoring patiromer(p<001); K >5.5 in 7% v25% (p=0.015);Spironolactone 50mg/day in 91% v. 74%(p=0.019);Hypokalemia (<3.5) in 6%v. 0%

OPAL-HK

N=243

Pitt B et al. European J Heart Failure 2015;17:1057-65.

Baseline K 5.1 to 6.5And

CKD Stages 3 or 4 (15 to60 mL/min), on a stabledose of ≥ 1 RAASi for ≥28 days.

Excluded HF Stage 4,DM1, OHT or kidneytransplant

42% HF (65% NYHAClass II), 44% CKD3, DM54%

N=102 with HF

Dual RAASi 25 (25%)ACEI 70 (69%) ARB 36 (36%) AA 20 (20%)

38% mild hyperK; 62% moderate to severe

Phase 1 (4 weeks):4.2 or 8.4 gramspatiromer BID based oninitial K levelPhase 2 (8 weeks):49 HF patientsrandomized to patiromerONCE daily (n=27) orplacebo (n=22) if K hadreduced to 3.8 to < 5.1during phase 1.Treatment algorithm forhyperK/hypoK

At 4 weeks, mean changein K was -1.06±0.05 mEq/L(p<0.001); 76% met thetarget rangeAt 12 weeks, recurrence ofhyperK (> 5.5) in 8%patiromer group v. 52% ofplacebo (p<0.001). RAASicontinued in 100%patiromer group v 55%placebo

PatiromerLimitations:1) Binding Issues:

• Of the oral medications studied with patiromer(n=28), 50% bound to the drug. Medications NOT found to bind: lisinopril, valsartan, spironolactone

• Drugs of concern: amlodipine, furosemide, levothyroxine, metoprolol

• ALL other medications need to be taken at least 3 hours before or after patiromer

2) Lack of data in OHT patients: • Binding to Mycophenolate?

• Effectiveness in patients on CNIs?

3) Maximum study duration: • 12 weeks in HF patients

Dose:• Starting Dose = 8.4 grams once daily with food • Adjust dose by 8.4 grams daily at one week intervals • Maximum dose = 25.2 grams dailyAdministration:• Add 1 ounce water to empty cup• Empty drug contents into cup• Stir thoroughly • Add additional 2 ounces water to admixture in cup• Stir thoroughly; will appear cloudy• Drink immediately; Add water if needed to residue in

cup

https://www.fda.gov/downloads/Drugs/DrugSafety/UCM574818.pdf

UPDATE: Sodium Polystyrene and Medication Binding


• ACPE#:

• Activity Type:

4. Assessment QuestionWhich of the following statements is correct regarding treatment of hyperkalemia in a patient with HF on guideline-directed therapies?

A. Treatment is only indicated when K exceeds 5.5 mEq/L B. Modifiable factors include diet and drugs such as NSAIDs,

trimethoprim, and some herbal preparations C. Aldosterone antagonist dosing should be reduced by 50%D. All guideline-directed therapies must be discontinued

temporarily until hyperkalemia is resolved

The Big Question – Treatment What is your recommendation for management of hyperkalemia in this case?

A) Reduce dose of sacubitril/valsartan

B) Discontinue spironolactone

C) Prescribe sodium polystyrene sulfonate15 grams x 1 with repeat lab

D) Prescribe patiromer 8.4 grams daily x 2 doses then repeat labs

E) No treatment at this time; repeat lab in 24 hours

The Case: Vincent

• Chronic hyperkalemia not responsive to diet alone

• Responding well to guideline-directed therapies

• Sacubitril-valsartan 49/51 mg BID, spironolactone 12.5 mg po daily, carvedilol 6.25 mg po BID

• Asymptomatic hyperkalemia; NSR

• K 5.6; crcl ~ 61 mL/min; AIC 5.5%

The Decision (and the Role of the Pharmacist)

• Patiromer 8.4 grams once daily

• Repeat labs in 48 hours

• No change in dosing of guideline directed therapies

Pharmacist’s Role:

• Process prior authorization • Assess affordability of agent • Ensure access to medication

(availability)• Counsel patient on expected side

effects • Counsel patient on need to space

dosing • Administer patiromer in mid-

day with meal • Re-educate on avoidance of K rich

foods• Call back in 48 hours to ensure that

patient went to the lab

https://www.heart.org

A helpful checklist to consider for discharging patients from clinic and for follow-up phone calls

Follow-Up:

K was 4.6 mEq/L in 3 days; patient continued on patiromer as daily therapy One month later: patiromer dosing three times a week

Ten Considerations to Improve Adherence1. Capitalize on opportunities when patients are most disposed to adherence In-hospital/pre-discharge initiation following decompensation

2. Consider the patient’s perspective Start with the goals of therapy (feeling better and living longer)

and then discuss how specific actions (medication initiation, intensification, monitoring, and adherence) support those goals Use decision aids when available Ask patient how they learn best and provide education

accordingly

3. Simplify medication regimens whenever possible

Ten Considerations to Improve Adherence

Yancy et al. JACC. 2017. Published ahead of print. Available at: http://www.onlinejacc.org/content/early/2017/12/12/j.jacc.2017.11.025. Accessed January 13, 2018.

4. Consider costs and access Become familiar with and advocate for systems that help make

cost sharing automatic, immediate, and transparent Prescribe lower-cost medications if of similar efficacy Facilitate access to copay assistance Discuss out-of-pocket copays proactively Prescribe 90-day quantities for refills

5. Communicate with other clinicians involved in care, ideally facilitated by electronic health records



6. Educate using practical, patient-friendly information Provide a written explanation of the purpose of each medication prescribed Plan pharmacist visits for complex medication regimens Use the “teach back” principle to reinforce education

7. Recommend tools that support adherence in real time Pill boxes to be filled by patient or caregiver a week at a time Alarms for each time of the day medications are due Smartphone M-Health applications that provide an interactive platform for

education, reminders, warnings, and adherence tracking

8. Consider behavioral supports Motivational interviewing Participate in engaged benefit designs



9. Anticipate problems Communicate common side effects Provide instructions on when to call for refills or problems

10. Monitor adherence and target patients at risk Ask patients directly (e.g., “How many times in a week do you miss taking your

medications?” “Have you run out of your medications recently?”)

Carry out medicine reconciliation at visits, with focus on discrepancies Assess remaining dosage units (i.e., count excess remaining tablets) Review available drug levels (e.g., digoxin, INR) or concentrations of BNP/NT-proBNP Plan home-based nursing visits for appropriate patients

The Wrap Up

Physical assessment can be a powerful tool when evaluating patients with heart failure and titrating drug therapy.

Both iron deficient anemia and hyperkalemia are common comorbidities in patients with heart failure which warrant close coordination of care.

With a solid understanding of the consultation process as well as having the appropriate educational and assessment tools, pharmacists can make significant impacts on outcomes in patients with heart failure.

Patient Tools

www.heartfailurematters.org

www.heartfailurematters.org

Documents

The Beat Goes On: How to Assess Patients with Heart … · Discuss patient assessment tools that are appropriate for pharmacists to use when assessing patients with heart failure;