HFrEF Treatment

What is the general approach for initiating drugs in HFrEF

Initiate as many mortality reducing drugs as the patient can tolerate and then titrate up to target doses

Which decreases mortality in HF patients the most: adding a new class of medication or increasing the dose of the medications they are on?

Adding a new class of medications

What gives the most mortality reduction in HF patients?

Target doses of all GDMTs!!

If a patient is newly diagnosed with HFrEF when should they achieve maximally tolerated or target doses of GDMT medications?

3 months

If a patient is discharged from the hospital for HFrEF when should they achieve maximally tolerated or target doses of GDMT medications?

6 weeks

Which medication classes should be given to a heart failure patient first?

ARNI (or ACEi/ARB), Beta-blocker, MRA, and SGLT inhibitors

When should a HFrEF patient be put on a diuretic (loop diuretic)?

if they are experiencing persistent volume overload (any signs of congestion/hypervolemia) even after taking max doses of GDMT meds

When should a HFrEF patient be put on hydralazine/isosorbide dinitrate?

If they are an African American that is persistently symptomatic and on other GDMT meds

When should a HFrEF patient be put on ivabradine?

Patients with a resting HR >= 70 bpm on maximally tolerated beta-blocker and in sinus rhythm (may or may not have symptoms)

When should a HFrEF patient be put on vericiguat?

patients on GDMT meds with worsening HF evidenced by HF hospitalization or requirement for IV diuretics

After starting Entresto what should be assessed in 1-2 weeks?

tolerability, BP, electrolytes, and renal function

When do you increase the dose of Entresto?

every 1-2 weeks increase the dose stepwise to a target of 97/103 mg twice a day

Which patients start on the lower dose of Entresto?

patients already on a daily equivalent of <= 10 mg enalapril or <= 160 mg valsartan, ACEi/ARB naive, eGFR < 30 mL/min/1.73m2, >= 75 years old

Which patients start on the higher dose of Entresto?

On equivalent of > 10 mg of enalapril or > 160 mg valsartan

When should a HF patient get an ACEi/ARB instead of an ARNI?

if the patient is not able to get/take Entresto for various reasons.

what should be assessed in 1-2 weeks after starting an ACEi/ARB

tolerability. BP, electrolytes, renal function

When do you increase the dose of an ACEi/ARB in patients with HFrEF

every 1-2 weeks and increase the dose stepwise to target doses

What are the starting dose options for sacubitril/valsartan

24/26 mg or 49/51 mg twice a day

What are the starting dose options for lisinopril

2.5-5 mg once a day

What are the starting dose options for valsartan

40 mg twice daily

What is the target dose for sacubitril/valsartan

97/103 mg twice daily

What is the target dose for lisinopril

20-40 mg daily

What is the target dose for valsartan

160 mg twice daily

How many days do you wait to assess tolerability, BP, electrolytes, and renal function in patients starting an MRA?

in 7 days

When do you increase the dose for MRAs

increase the dose stepwise at least every 2 weeks to target dosing and monitoring appropriately

Contraindications for MRAs in HFrEF

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

Special monitoring for MRAs in HFrEF

electrolytes and renal function 7 days after initiation/titration - after a stable dose check these monthly for 3 months and then every 3 months out to a year

Starting dose for spironolactone

12.5-25 mg once daily

Target dose for spironolactone

25-50 mg once daily

How do the doses of MRAs differ for heart failure compared to patients with HTN?

The doses are lower than what is generally used for HTN

Which SGLT inhibitors do you have to check that the patients eGFR is >= 25 g/mL/1.73m2?

dapagliflozin and sotagliflozin

when do you increase the dose of sotagliflozin

increase the dose stepwise to the target dosing in 2 weeks

Contraindications for SGLT inhibitors

Patients with type I diabetes

Starting dose for dapagliflozin

10 mg once daily

Starting dose for empagliflozin

10 mg daily

Target dose for dapagliflozin

10 mg daily <3

Target dose for empagliflozin

10 mg once a day

Can empagliflozin and dapagliflozin be titrated up from 10 mg?

Yes, if concomitant diabetes for glucose control

starting dose of sotagliflozin

200 mg daily

target dose of sotagliflozin

400 mg daily

What needs to be monitored when using beta-blockers in HFrEF

monitor HR and BP after initiation and during titration

When do you increase the dose of beta-blockers in HF

increase the dose every 2 weeks stepwise to target dosing

starting dose of bisoprolol

2.5 mg daily

target dose of bisoprolol

10 mg daily

starting dose of metoprolol succinate

12.5-25 mg once a day

target dose of metoprolol succinate

200mg daily

Starting dose of carvedilol

3.125-6.25 mg twice daily

target dose of carvedilol

25 mg twice daily

if > 85 kg give patient 50 mg twice daily

What to monitor after giving loop diuretics?

bp, electrolytes, and renal function after initiation and during titration!

When do you titrate the dose of loop diuretics?

titrate to relief of congestion which may be over days or weeks - increase as needed to maintain euvolemia and to

What is the usual start dose of furosemide?

~20-40 mg orally

Why are frequent clinic visits needed for loop diuretics

Need frequent clinic visits until patient is titrated to optimal effect, and may need to prescribe PO potassium in conjunction

If patients have increased distal sodium reabsorption from chronic loop diuretic use what med can be added on?

A thiazide

If a patient has poor delivery of the loop diuretic to the site of effect due to reduced GFR, HF, or gut edema, what can be done?

Increase the dose of loop diuretic

Furosemide 20 mg IV is equivalent to what dose orally?

40 mg

Furosemide 20 mg IV is equivalent to what dose of IV torsemide?

20 mg

Furosemide 20 mg IV is equivalent to what dose of IV bumetanide

1 mg

Furosemide 20 mg IV is equivalent to what dose of IV ethacrynic acid

50 mg

Furosemide 40 mg orally is equivalent to what dose of oral torsemide

20 mg

Furosemide 40 mg orally is equivalent to what dose of oral bumetanide

1 mg

Furosemide 40 mg orally is equivalent to what dose of oral ethacrynic acid

50 mg

Torsemide 20 mg IV is equivalent to what dose orally?

20 mg

Bumetanide 1 mg IV is equivalent to what dose orally?

1 mg

ethacrynic acid 50 mg IV is equivalent to what dose orally?

50 mg

What needs to be monitored when starting hydralazine/isosorbide dinitrate/combo pill

Bp after initiation and during titration

When do you need to increase the dose of hydralazine/isosorbide dinitrate/combo pill

increase the dose every 2 weeks stepwise until at target dosing

hydralazine target dose

75 mg TID

Isosorbide dinitrate target dose

40 mg TID

BiDil target dose

2 tablets TID

What needs to be confirmed before starting ivabradine

confirm beta-blocker is at maximally tolerated/targeted dose and that patient is in sinus rhythm

When to reassess HR in patients and increase stepwise to target dosing using ivabradine

in 2-4 weeks

How to titrate ivabradine in patients with a 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

How to titrate ivabradine in patients with a HR 50-60 bpm

maintain current dose and monitor HR

How to titrate ivabradine in patients with a HR > 60 bpm

increase by 2.5 mg twice daily until maximum dose of 7.5 mg twice daily

Pearl for ivabradine

Take with food!!!!

Starting dose of ivabradine

2.5 mg twice daily with food

target dose of ivabradine

7.5 mg twice daily with food!!

What needs to be confirmed before starting a patient on vericiguat

Confirm EF < 45% on maximally tolerated GDMT and has worsening symptoms (recent hospitalization or need for IV diuretics) along with a negative pregnancy test

What needs to be monitored in patients using vericiguat

BP and CBC (anemia) during initiation and titrate

Pearl for vericiguat

Take with food !!

starting dose of vericiguat

2.5 mg daily with food

target dose of vericiguat

10 mg daily with food

Other (rare) therapy options for patients with symptomatic HFrEF and possibly arrhythmias?

digoxin (2b recommendation)

What is an additional therapy that can be used for patients with HF NYHA II-IV?

polyunsaturated fatty acids (PUFA) (2b recommendation)

What is an additional therapy that can be used for patients with HF and hyperkalemia when taking RAASi

potassium binders (2b recommendation)

When may digoxin be added to a medication regimen?

If patient is already on other GDMT and patient is still symptomatic

What are the risks associated with digoxin

cardiac arrhythmias, GI symptoms (anorexia, N/V), neurological symptoms (visual disturbances, disorientation, confusion)

Target plasma concentration for digoxin used in HF

0.5-0.9 ng/mL

Can you develop digoxin toxicity if your plasma concentration is at target (0.5-0.9 ng/mL)?

Yes 😟

Why should you avoid Non-DHP CCBs in HFrEF?

Can worsen EF/CO

Why should you avoid class IC antiarrhythmic drugs and dronedarone in HFrEF?

Increased mortality

Why should you avoid thiazolidinediones in HFrEF?

worsens HF symptoms and hospitalizations

Why should you avoid DPP-4s (saxagliptin and alogliptin) in HFrEF?

increases HF hospitalizations

Why should you avoid NSAIDs in HFrEF?

Worsens HF symptoms (fluid overload)