1. Initiate as many mortality reducing drugs as patient can tolerate, then titrate up to target doses 2. Target doses of all GDMT = most mortality reduction 3. A little of everything is better than a lot of a few things

1. If de novo HFrEF, achieve maximally tolerated or target doses within 3 months 2. If discharged from hospital for HFrEF, achieve maximally tolerated or target doses within 6 weeks

Treatment Approach: HFrEF Flashcards by Samantha Sanders

Morbidity and Mortality Reducing Drugs

Guideline Directed Medical Therapy

RAAS Inhibition
ARNI, ACEI,ARB
MRAs
Spironolactone, Eplerenone
SGLT Inhibitors
Empagliflozin, Dapagliflozin, Sotagliflozin
Beta Blockers
Carvedilol, Metoprolol Succinate, Bisoprolol

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Morbidity Reducing Drugs

1.Diuretics
* Loop diuretics

2.If Channel Inhibitor
* Ivabradine (Corlanor)

3.Soluble guanylate cyclase stimulator
* Vericiguat (Verquvo)

4.Cardiac Glycoside
* Digoxin (Lanoxin)

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General Approach

Initiate as many mortality reducing drugs as patient can tolerate, then titrate up to target doses
Target doses of all GDMT = most mortality reduction
A little of everything is better than a lot of a few things

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Treatment Goals

If de novo HFrEF, achieve maximally tolerated or target doses within 3 months
If discharged from hospital for HFrEF, achieve maximally tolerated or target doses within 6 weeks

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HFrEF treatment

for patients with persistent volume overload

add/titrate diuretic agent (loop diuretics)

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HFrEF treatment

persistently symptomatic AA patients on other GDMT

add hydralazine/isosorbide dinitrate (vaso/veno dilators)

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HFrEF treatment

patients w/ a resting HR ≥ 70 bpm on maximally tolerated beta- blocker and in sinus rhythm

add ivabradine

don’t need to be symptomatic

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HFrEF treatment

patients on GDMT with worsening HF evidenced by hospitalization or requirement for IV diuretics and EF < 45%, confirm patient is not pregnant

add vericiguat

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ARNI starting dose requirements

24/26 mg twice daily

on 10 mg or less of enalapril
on 160 mg or less of valsartan
ACEI/ARB naive
eGFR is less than 30 mL/min/1.73 m2
75 yrs old or older

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ARNI starting dose requirements

49/51 mg twice daily

on more than 10 mg enalapril
on more than 160 mg valsartan

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ARNI monitoring criteria

1-2 weeks: assess tolerability, monitor BP, electrolytes, renal function

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ARNI target dose

97/103 mg twice daily

every 1-2 wks, increase dose step wise to this dose

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ACEI/ARB monitoring criteria

1-2 weeks: assess tolerability, monitor BP, electrolytes, renal function

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ACEI starting dose

lisinopril 2.5-5 mg daily

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ACEI target dose

20-40 mg daily

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ARB starting dose

valsartan 40 mg twice daily

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ARB target dose

160 mg twice daily

every 1-2 weeks, increase dose stepwise to target doses

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MRA monitoring criteria

7 days: assess tolerability, monitor BP, electrolytes, renal function
after stable dose: check monthly for 3 months then every 3 months out to a year

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MRA contraindications

eGFR < 30 mL/min/1.73 m2
creatinine > 2.5 mg/dL in men
creatinine > 2 mg/dL in women

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MRA starting dose

spironolactone 12.5-25 mg daily

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MRA target dose

25-50 mg daily

increase dose stepwise at least every 2 weeks to target dose

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SGLT inhibitors starting criteria

ensure eGFR of 25 mg/ml/1.73 m2 for dapagliflozin and sotagliflozin
contraindicated in patient with T1DM

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SGLT2 inhibitors starting and target dose

dapagliflozin (farxiga) 10 mg daily
empagliflozin (jardiance) 10 mg daily

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SGLT1 inhibitors starting dose

sotagliflozin (inpefa) 200 mg daily

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SGLT1 inhibitors target dose

sotagliflozin 400 mg daily ## Footnote increase dose stepwise to target dosing in 2 weeks

evidence based beta blockers monitoring criteria

monitor HR and BP after initiation and during titration ## Footnote increase dose every 2 weeks stepwise to target dosing

beta blocker starting dose | bisoprolol (zebeta)

2.5 mg daily

beta blocker target dose | bisoprolol (zebeta)

10 mg daily

beta blocker starting dose | metoprolol succinate (toprol XL)

12.5-25 mg daily

beta blocker target dose | metoprolol succinate (toprol XL)

200 mg daily

beta blocker starting dose | carvedilol (coreg)

3.125-6.25 twice daily

beta blocker target dose | carvedilol (coreg)

* 25 mg twice daily * > 85 kg: 50 mg twice daily

loop diuretics monitoring criteria

monitor BP, electrolytes and renal function after initiation and during titration | titrate to relief of congestion over days-weeks

when to add loop diurectics

* if patients are experiencing any signs of congestion (hypervolemia)

loop diuretics: threshold

* have to hit a specific drug concentration to make patient urinate some amount that is specific to that patient * threshold is different for every patient ## Footnote Increase threshold: * Chronic use * AKI/CKD * Heart failure (gut edema)

loop diuretics: ceiling

* once we reach threshold even if we increase the dose the amount of urine output would only be incremental * would have to increase dose frequency to get increased urine output

diuretic resistance

1.increased distal sodium reabsorption (chronic loop diuretic use) * add thiazide to loop 2.poor delivery to site of effect (kidneys): reduced GFR, HF, gut edema * increase dose of loop diuretic

loop diuretics: dosing

furosemide (oral/iv): 40 mg/20 mg torsemide (oral/iv): 20 mg/20 mg bumetanide (oral/iv): 1 mg/1 mg ethacrynic acid(oral/iv): 50 mg/50 mg

hydralazine/isosorbide dinitrate monitoring criteria

monitor BP after initiation and during titration

hydralazine (apresoline) starting dose

25 mg TID

hydralazine target dose

75 mg TID

isosorbide dinitrate starting dose

20 mg TID

isosorbide dinitrate target dose

40 mg TID

BiDil (20 mg isosorbide nitrate + 37.5 mg hydralazine) starting dose

1 tablet TID

BiDil (20 mg isosorbide nitrate + 37.5 mg hydralazine) target dose

2 tablets TID

titration schedule for vaso/venodilators

increase dose every 2 weeks stepwise to target dosing

ivabradine monitoring criteria

2-4 weeks: reassess HR and increase stepwise to target dosing

how to titrate ivabradine

* HR < 50 bpm or symptoms of bradycardia: reduce dose by 2.5 mg twice daily or discontinue if already at 2.5 mg twice daily * HR 50-60 bpm: maintain current dose and monitor heart rate * HR > 60 bpm: increase by 2.5 mg twice daily until maximum dose of 7.5 mg twice daily | take with food

ivabradine (corlanor) starting dose

2.5 mg twice daily with food

ivabradine (corlanor) target dose

7.5 mg twice daily with food

vericiguat (verquvo) monitoring criteria

monitor BP and CBC (anemia) during initiation and titrate

vericiguat titration schedule

double the dose every 2 weeks until target dose is achieved

vericiguat (verquvo) starting dose

2.5 mg daily with food

vericiguat (verquvo) target dose

10 mg daily with food

symptomatic HFrEF | additional therapies

digoxin

HF NYHA II-IV | additional therapies

polyunsaturated fatty acids (PUFA)

HF with hyperkalemia when taking RAASi | additional therapies

potassium binders

when to add digoxin

if already on other GDMT and patient is still symptomatic

risks associated with digoxin

1. cardiac arrhythmias 2. GI symptoms: anorexia, nausea, vomiting 3. neuro symptoms: visual disturbances, disorientation, confusion

digoxin toxicity

1. plasma concentration target 0.5-0.9 ng/mL 2. patients can still develop toxicity in this range

consequences in HFrEF when administrating Non-DHP CCBs

worsening of EF/CO

consequences in HFrEF when administrating Class IC antiarrhythmic drugs and dronedarone

increased mortality

consequences in HFrEF of administrating thiazolidinediones

worsening HF symptoms and hospitalizations

consequences in HFrEF of administrating DPP-4s (saxagliptin and alogliptin)

increased HF hospitalizations

consequences in HFrEF of administrating NSAIDs

worsen HF symptoms (fluid overload)