Heart Failure Therapeutics I

perfusion

Heart failure is a _________ issue related to decrease CO.

preload

volume of blood in ventricles at end of diastole (end diastolic volume)

afterload

pressure required for ventricle to push blood out (systemic vascular resistance)

contractility

ventricle's ability to squeeze

frank-starling mechanism

More preload = more ventriclestretch = ↑ myocardial contractionstrength = ↑ SV and CO

HF

inability of the heart to provide sufficient output to meet the demands of the body

-prevent hospitalizations and reduce mortality

-control symptoms

-provide optimal patient education

What are the overall goals of HF therapy?

guideline directed medical therapy

GDMT

BB

What drug class have the best decrease for overall mortality?

-loop diuretics

-digoxin

-ivabradine

What drugs are used in HF that do not decrease mortality?

Stage A tx

-tx HTN, DM, DLD-reduce risk (consider ACE/ARB)

-risk factor reduction, education of patient and family

Stage B tx

ACE/ARB (maybe BB in selected pts)

Stage C tx

-ACE/ARB/ARNI, BB, MRA and SGLT2 in all pts (ARNI preferred)

-loop diuretics for all pts needing diuresis

-Verquvo and BiDil for selected pts

-Digoxin and Corlanor to lower morbidity

Stage D tx

-home inotropes

-transplant/LVAD

-hospice

HF TLC

-Fluid restriction

-Limit sodium

-Limit alcohol

-Avoid nicotine

-Weight management

-Manage other risk factors (BP, lipids, etc.)

-Exercise

-Decrease stress

-Vaccinations

HFrEF for fluid

-salt and fluid restrictions

-loop diuretics

-thiazides and AA/MRAs

-metolazone

loop diuretics

mainstay of therapy for fluid (HFrEF)

salt and fluid restrictions

great and free for HFrEF fluid

thiazides and AA/MRAs

okay for fluid but better for BP (HFrEF)

Metolazone

really strong thiazide like and good for acute tx (HFrEF)

ethacrynic acid

What loop diuretic should you use for edema in a pt with a sulfonamide allergy?

AEs of Loop Diuretics

hypotension, ototoxicity, rash, hyperuricemia,worsening renal function, electrolyte abnormalities (↓ K+, &Mg++ are biggest issues)

oral and IV

What is the route of admin for loop diuretics?

renal function and electrolytes

What do you need to monitor in loop diuretics?

furosemide

What loop diuretic do you have to eat with?

Torsemide

What is the only loop diuretic that is QD?

Bumetanide

What loop diuretic has the shortest onset of action?

better

Torsemide has more predictable kinetics and may result in ________ diuresis than furosemide in heart failure patients.

Furoscix on body infuser

-SubQ self admin auto-infuser

-delivers 80 mg of furosemide over 5 hrs (30 mg over the first hour, then 12.5 mg/hr * 4 hrs)

-way to get "IV" furosemide at home without having to have IV access, ER or a nurse

-to keep people out of hospital or ED

no

Can you use Furoscix in an ER or true emergency situation?

Metolazone

-very strong thiazide like diuretic

-usually given prn or short term for unresponsive edema

In HF, a high amount of sodium reaches the distal collecting tubule. The combination ofthese agents helps combat this

Why are thiazides are synergistic with loops?

before due to a longer time to peak and want it to have similar onset of action as your loop

Why do you take thiazides 30 mins before your loop?

increase dose, change loops, add different diuretic, split doses, enhance TLC

What are the other ways to combat diuretic resistance rather than metolazone?

weight, BMP, and kidneys

What do you need to monitor with Metolazone?

SGLT-2 inhibitors

-all DM meds have to be assessed for CV safety

-benefits independent of renal function and glucose control

-Reduces fibrosis, remodeling, and myocardium injury

-Promotes natriuresis and diuresis, thus lowering edema

-Increases glucagon which increases CO, HR, & coronary bloodflow

preload, afterload, and remodeling

What do SGLT-2 inhibitors lower?

10 mg usually in AM

How many mg should you use daily of SGLT-2 inhibitors?

both

Do SGLT-2 inhibitors lower mortality or morbidity?

< 25

When should you use caution with SGLT-2 inhibitors in CrCl?

AEs of SGLT-2 inhibitors

-UTIs

-genital infections

-nasopharyngitis

in the morning (diuresis)

What should you tell patients taking SGLT-2 inhibitors?

SrCr, AEs, maybe glucose

What should you monitor with SGLT-2 inhibitors?

<70 bpm

What is the target HR?

beta blockers

-mainstay of therapy

-not all are included

beta blockers

give to all pts regardless of stage or class

both

Do beta blockers reduce mortality or morbidity?

Nebivlol

is not FDA approved or in the guidelines, but it can be used

-Metoprolol succinate

-Bisprolol

-Carvedilol

-Nebivolol

What are the 4 beta blocker drugs used in HF?

What are the possible reasons to avoid beta blockers in HF?

AEs of BB

-bradycardia

-ED

-vivid dreams

-sedation

-orthostasis

-bronchospasm

carvedilol

has to be given with food and max dose based on weight

Toprol XL

can be split, but Coreg CR can not

Carvedilol

-mixed alpha and beta affects

-BP > HR

-increase orthostasis

Metoprolol Succinate

-beta 1 specific

-affects HR > BP

-not tartrate salt

Bisoprolol

-beta 1 specific

-affects HR > BP

-hard titration

Nebivolol

-beta 1 and NO

-HR=BP

-has patient assistance

start slow and titrate slow to avoid worsening symptoms and causing exacerbation

What should you do when starting BBs?

Digoxin

inhibits Na+ and K+ ATPase pumps (positive iontropic action)

foxglove

What flower does Digoxin come from?

< 1

What is the target digoxin level?

class 3 and 4

What classes of HF used Digoxin?

morbidity

Does Digoxin have morbidity or mortality benefits?

life

Once you start Digoxin, you are on it for ______.

highly

Digoxin kinetics is ________ variable depending on renal function, absorption, and drug interactions.

DDIs with Digoxin

-Increase digoxin concentrations (thiazides, MRAs)

-Decease digoxin concentrations (antacids, St. John's wort)

-Increase its therapeutic effects (BBs, CCBs)

6

Levels of Digoxin should be drawn at least ____ hours post dose.

decrease

Higher fiber diet can _________ absorption and effects of Digoxin.

digoxin toxicity

-can happen with acute or chronic ingestion

-1st to appear = N/V/D, dizziness,

-Next to appear = yellow/green halos, confusion,weakness

-Last to appear = agitation, palpitations, heart block

Electrolyte abnormalities, dehydration, drug interactions, kidney dysfunction

What are the predisposing factors for Digoxin toxicity?

-hold/reduce dose

-activated charcoal/gastric lavage, DigiFab

What are the ways to treat Digoxin toxicity?

Ivabradine (Corlanor)

dosed BID with food titrate to resting HR of 50-60 bpm

AEs of Ivabradine (Corlanor)

-Bradycardia or atrial fibrillation

-Luminous phenomena (diplopia, enhanced brightness)

-Fetal toxicity

DDI with Ivabradine (Corlanor)

avoid strong CYP3A4 inducers and inhibitors

contraindications of Ivabradine (Corlanor)

-Bradycardia & heart block (or pacemaker dependent)

-Strong CYP3A4 inhibitors

-Severe hepatic impairment

-Max tolerated BB as not replacing them due to lack of mortality benefit

-EF ≤ 35 % & NYHA Class II - IV symptoms as this is who was studied

-Normal sinus rhythm due to arrhythmia risk

-HR > 70 bpm due to bradycardia risk

What is the prescribing criteria for Ivabradine (Corlanor)?

morbidity

Does Ivabradine (Corlanor) improve morbidity or mortality?

ACE/ARBs

-Class effect of ↓ mortality and morbidity

-Remember to monitor renal and potassium:

* Hyperkalemia & small (usually transient) ↑ SrCr

* At initiation and any dose increase

-Adverse effects

(Cough (ACEIs usually), angioedema, hypotension, rash, HA

angioedema, CKD or worsenrenal function, hypotension, hyperkalemia, renalartery stenosis, mod/severe aortic stenosis, pregnancy

What are the possible reasons to avoid ACEi/ARBs?

Aliskiren

hasnt been studied, isnt in the guidelines, or used for HF

all of them regardless of stage or class

What patients should receive an ACEi/ARB?

ARNI

Entresto drug class

-EF < or = 40%

-Class 2-4 symptoms

What is the dosing criteria for Entresto?

36

You must have a _____ hour washout if on an ACE.

24

You must have a ____ hour washout if on an ARB.

entresto

will lower BP better than ACEi/ARB monotherapy

current ACEi/ARB dose, renal, and hepatic function

What is the starting dose of Entresto based off?

q 2-4 weeks

How should you titrate Entresto?

beat

Entresto _______ Enalapril with regards to reduction in CV death or hospitalization for heart failure.

Hydralazine/ISDN (BiDil)

used to reduce preload and afterload

African Americans

What ethnic group is known for reduction in mortality with BiDil?

hydralazine AEs

orthostasis, reflex tachycardia, drug-induced lupus

Nitrates AEs

HA, orthostasis, reflex tachycardia

no

Does BiDil require monitoring outside of AEs and BP?

5-6 tabs (still dosed BID-TID with food)

What is the target dose ______ for BiDil?

HA

What is the worst AE with BiDil?

Split up the drugs into 2 pulls but keep in mind target dose

Most insurance doesnt cover BiDil so what can you do?

Spironolactone and Eplerenone

-Both demonstrated mortality and morbidity benefits

-Avoid if SrCr ≥ 2.5 (GFR < 30) or K+ ≥ 5.0

-Watch for hyperkalemia combined with ACEIs, ARBs, & ARNIs

-Check BMP at 3 days, then 7 days, & monthly for 1st 3 months atinitiation or dose changes

-Both are once daily, but may need BID dosing for better effect

-HF doses are generally lower than those for HTN

Spirnoloactone (Aldactone)

-cheapest option

-AEs: androgenic issues

-can affect glucose and uric

Eplerenone (Inspra)

-lacks androgenic AEs

-AEs: angina, GI complaints

-CI: strong CYP3A4 inhibitors