Chronic and Acute Anita Ralstin, MS, CNS, BC, CNP-BC - PowerPoint Presentation

Slide1

Chronic and AcuteAnita Ralstin, MS, CNS, BC, CNP-BC

The Pharmacology of Heart Failure with Reduced Ejection Fraction (

HF

r

EF

)

Slide2

I have no conflicts of interest.

Slide3

HFrEF vs HFp

EF

Left ventricular failure with reduced EF is now noted as

HF

r

EF

(heart failure with reduce ejection fraction)

Previous diastolic heart failure is

now

noted as

HF

p

EF

(heart failure with preserved ejection fraction)

Slide4

Impact of Heart Failure (HF)Approximately 4.6 million American are living with heart failure.

Annual number diagnosed: 450,000

Mortality: decreasing, but remains high

Researchers predict > 8 million by 2030

2012 direct cost for HF was $20.9 billion, projected to be $53 billion by 2030

Heart Failure Society of America;

www.hfsa.org

; K. Fitch, P

Pelizzari

, B

Pyenson

; The High Cost of Heart Failure for the Medicare Population: An Actuarial Cost Analysis 2/2015

Slide5

Complex Pathophysiology of HF

The Frank-Starling mechanism, in which an increased preload helps to sustain cardiac performance

Alterations in myocyte regeneration and death

Myocardial hypertrophy with or without cardiac chamber dilatation, in which the mass of contractile tissue is augmented

Activation of

neurohumoral

system

Norepinephrine release

Activation of renin-

angiotension

-aldosterone system

Activation of sympathetic nervous

system

Atrial

natruetic

peptide, vasopressin

Slide6

Classification of HFNew York Heart Classification

I,II,III, IV

ACC/AHA

Stages

Stage A

Stage

B

Stage C

Stage D

Slide7

Stage A PharmacologyPrevention

Hypertension management

CAD prevention

Diabetes management

Metabolic syndrome management

Treat ETOH abuse

Slide8

Stage B PharmacologyDeveloped structural heart disease without symptoms of HF

Initiate ACE-I or ARB

Initiate Beta Blocker therapy

Aldosterone Blocking

Slide9

ACE-I/ARBRenin-

angiotension

-aldosterone system (RAAS) activation

Compensatory mechanism to maintain cardiac output

Increasing evidence of local RAAS at the tissue level (heart, kidney and vasculature)

Angiotension

II is a potent vasoconstrictor, triggers SNS and adrenal release of aldosterone

Ace Inhibitors were found to improve survival in CHF patients

Delay onset & progression of HF in pts with asymptomatic LV dysfunction

↓ cardiac remodeling

Slide10

Common ACE-Ibenazepril (

Lotensin

)

captopril (

Capoten

)

enalapril (Vasotec,

Epaned

)

fosinopril

(

Monopril

)

lisinopril

 (

Prinivil

, Zestril)

moexipril

 (

Univasc

)

perindopril (

Aceon

)

quinapril (

Accupril

)

ramipril

 (

Altace

)

trandolapril

 (

Mavik

)

Slide11

ACE-I Side EffectsAngioedema

Hypotension

Renal insufficiency

Rash

Cough

Monitor renal function and potassium levels

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ARBConsidered equivalent to ACE-I

Less cough due to reduced bradykinin release.

Minimal evidence supporting using ACE-I and ARB together.

Slide13

Common ARBsAzilsartan (

Edarbi

)

Candesartan (

Atacand

)

EprosartanIrbesartan

(Avapro)

Losartan (

Cozaar

)

Olmesartan

(Benicar)

Telmisartan

(

Micardis

)

Valsartan (Diovan)

Slide14

ARB Side EffectsLess cough than ACE-I

Similar SE profile as ACE-I

Slide15

Beta Blockers (BB)Reduce the effect of the sympathetic nervous system (beta receptors)

Reduce heart rate to allow improved left ventricular filling

Some relax blood vessels to reduce afterload.

Start with ACE-I/ARB as there is a synergic effect

Start with low doses and advance.

Slide16

Approved BB for Heart FailureCarvedilol

Bisoprolol

Metoprolol XL

These have shown to slow progression of HF, prolong survival and reduce ventricular arrhythmias

Slide17

Side Effects of BBFeeling fatigued

Hypotension

Bradycardia

Cold hands/feet

Worsening asthma s/s

Hair loss

Slide18

Stage C Heart FailureStructural changes with s/s of heart failure

Continue use of approved BB and ACE-I/ARB

Add aldosterone blocking agent

Replace ACE-I/ARB with valsartan/

sacubitril

(

Entresto

)

Consider

ivabradine

(

Corlanor

)

Slide19

Aldosterone BlockadeAldosterone has been shown to cause coronary inflammation, cardiac hypertrophy, myocardial fibrosis, ventricular arrhythmias, and ischemic

lesions

. 

Two medications

s

pironolactone

e

plerenone

Indicated for those with EF 35% or less. Stage B or C.

Do not use if CR 2.5 in men or 2.0 in women or potassium 5.0 or higher.

Stop potassium supplementation, monitor and restart if needed.

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spironolactoneNon-selective blocker leads to increased incidence of gynecomastia,

Dose 12.5 to 25 mg daily.

May reduce dose to QOD for GFR 30-49.

Monitor renal function and potassium levels at onset and 1 week post implementation, then monthly for first 3 moths.

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eplerenoneConsidered to be ½ as potent as spironolactone.

Dose 25 mg daily.

May reduce dose to QOD for GFR 30-49.

Monitor renal function and potassium levels at onset and 1 week post implementation, then monthly for first 3 moths.

Slide22

Valsartan/sacubitril

ARB (valsartan)

is combined with an inhibitor of

neprilysin

, an enzyme that degrades natriuretic peptides, bradykinin,

adreno-medullin

, and other vasoactive peptides.

In

an RCT that compared the first approved ARNI, valsartan/

sacubitril

, with

enalapril

in symptomatic patients with

HF

r

EF

tolerating an adequate dose of either ACE inhibitor or ARB, the ARNI reduced the composite endpoint of cardiovascular death or HF hospitalization significantly, by 20%

C.

Yancy

, et.al: 2016 ACC/AHA/HFSA Guideline for the Management of Heart Failure

Slide23

Valsartan/sacubitrilOn ACE-I/ARB

Allow 36 hour washout

Start at 49/51 BID dose

Not on ACE-I/ARB or severe renal impairment

Start at 24/26 BID

Increase every 2-4 weeks to target maintenance dose of 97/103 BID

Slide24

Side Effects valsartan/sacubitril

Hypotension

Impaired renal function

Angioedema

Hyperkalemia

Cost

$

12.50/day; $4500/year

Slide25

ivabradine (Corlanor)

Indications: heart rate reduction

Corlanor

(

ivabradine

) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use

Corlaor

P

rescribing

I

nformation 1/2017

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ivabradine (Corlanor)

Up titrate BB first.

For patients on maximum tolerated medical therapy with

sinus

rhythm and resting heart rate > 70 BPM.

Initiate at 5 mg BID, assess at 2 weeks and up titrate to 7.5 mg BID to maintain resting HR between 50-60 BPM

Reduce dose to 2.5 mg BID or stop medication if resting HR < 50 BPM

Slide27

ivabradine (Corlanor)

Contraindications

Acute decompensated HF

BP < 90/50

SSS, AV Block unless pacemaker in place

Sinus bradycardia

Use with strong CYP3A4 inhibitors -incomplete list

Alprazolam, carbamazepine, colchicine, cyclosporine, dexamethasone,

disopyramide

, fluticasone, lovastatin,

repaglinide

, sildenafil, simvastatin,

tadalafil

,

triazolam

Slide28

ivabradine (Corlanor)

Side Effects

Fetal toxicity

Atrial fibrillation

Bradycardia and conduction disturbances

Syncope

Ventricular arrhythmias

Cost

About $375/month

Slide29

DiureticsUsed for fluid volume management

Use lifestyle changes to reduce the dependence on diuretics.

Loop diuretics are most effective.

f

urosemide

t

orsemide

b

umetanide

Slide30

Pearls for DiureticsIf loosing effectiveness, switch to another loop for a time

Add

metolazone

2.5 to 5 mg PO 30 minutes before diuretic dose.

Educate the patient on s/s of dehydration

Prescribe just a few tablets

Monitor and replace potassium and magnesium.

Slide31

DigoxinMay be considered in HF patients to reduce hospitalization.

Narrow therapeutic window

Toxicity

Anorexia

Nausea, vomiting

Headache

Disorientation.

Slide32

VasodilatorsReduction of afterload

by arteriolar vasodilatation (hydralazine)



reduce LVEDP, O

2

consumption, improve myocardial perfusion,



stroke volume and COP

Reduction of preload

By

venous dilation

(nitrate

)



↓ the venous return



↓ the load on both ventricles.

Usually the maximum benefit is achieved by using agents with both action.

Use when intolerant to ACE-I/ARB.

Slide33

VasodilatorsMonitor BP and renal function.

Headache common SE of nitrates and hydralazine.

Hydralazine also can cause nausea, vomiting, diarrhea and orthostatic hypotension.

Slide34

Stage DEnd stage heart failure

Medications continue as long as HR and BP can be sustained.

Wean medications when BP cannot be sustained.

Consider advanced heart failure therapies or inotropic support.

Slide35

Acute Decompensated Heart FailureCommon and potentially fatal

Maintain outpatient HF medications as possible

Usually present with acute dyspnea from pulmonary edema

Can also present with signs of low output: fatigue, marked exercise intolerance, anorexia, cognitive impairment

Slide36

Acute Decompensated Heart FailureTreatment Goals

Goals

Hemodynamic stabilization

Support oxygenation and ventilation

Symptom relief

Modalities

Diuresis

Supplemental oxygen and assisted ventilation

Vasodilator therapy in some patients

Inotropes

Arrhythmia Management

Slide37

Diuresis and VasodilationMainstays of therapy

Flash pulmonary edema

with

HTN

Diuresis and aggressive vasodilation

Normotensive and volume overload

Diuresis and vasodilation

Hypotension and volume overload

Diuresis +/- inotropes

Aortic Stenosis

Diuresis

with caution

Slide38

DiureticsIV preferred over PO because of better bioavailability; bypasses GI congestion

Common initial doses: furosemide 40 mg, bumetanide 1 mg,

torsemide

10-20 mg

Rule of thumb: 1-2.5 times their normal PO dose

Peak diuresis is 30 minutes after administration

Bolus and continuous IV infusions have similar efficacy

Adding a thiazide diuretic (

metolazone

) can potentiate the effects of the loop diuretics

Slide39

VasodilatorsIV nitroglycerin or IV nitroprusside

Monitor BP to make sure hypotension does not develop

Nitrates are contraindicated with PDE-5 inhibitors like sildenafil

Nitroprusside

Don’t titrate above 400 mcg/min of nitroprusside (cyanide toxicity)

Can result in reflex tachycardia or rebound vasoconstriction

Slide40

InotropesConsider if hypotensive with severe systolic dysfunction

Can lead to ischemia (increased HR and myocardial oxygen consumption) or arrhythmias

Worse mortality if given to patients who do not critically need these meds

Dobutamine and dopamine: primarily beta-1 agonists

Milrinone: phosphodiesterase inhibitor

Slide41

Dopamine DobutamineCan be used at low dose to improve renal blood flow if diuresis is not adequate.

For cardiogenic shock, inotropes are used to support sufficient blood flow to preserve organ function.

Dopamine to improve cardiac contractility, initiate at 5-10 mcg/kg/min IV

Dobutamine has less MVO2 demand, may result in tachycardia. 0.5-1 mcg/kg/min IV

Slide42

NorepinephrineCatecholamine with alpha receptor activity (vasoconstriction) to treat hypotension

Increases afterload which could reduce cardiac output.

Increases myocardial oxygen consumption.

Dose for acute hypotension

Initial 8-12 mcg/min IV and titrate to effect

Maintenance

2-4 mcg/min IV

Slide43

MilrinoneA selective phosphodiesterase inhibitor in cardiac and vascular tissue.

Positive inotropic and vasodilator effects.

Dose 50 mcg/kg loading dose by IV push over 10 minutes then 0.375-0.75 mcg/kg/min.

Used in Stage D HF for symptom management as home infusion. Must demonstrate improvement in right heart pressures and symptoms to qualify.

Slide44

Thank you, Questions?