HFrEF Agent Pearls

The transition from which drug to which drug requires a wash-out period? How long is that wash-out period?

ACEi to ARNi

• ARNi should only be taken after waiting 36 hours following stopping ACEi — due to angioedema risk

• This does not apply to ARBs; if switching from ARB to ARNi, can schedule ARNi as next dose

Criteria to stop/hold/dose reduce ARNi/ACEi/ARB

• SCr increase >30% within 2-4 weeks of initiation/dose change

• SCr increase by ≥0.3 mg/dL within 48 hours after initiation/dose change

Which HFrEF drug falsely elevates BNP and makes it an unreliable marker of disease progression?

ARNis

Selectivity of metoprolol succinate?

Beta-1 selective

Selectivity of bisoprolol?

Beta-1 selective

Selectivity of carvedilol?

Beta-1 and -2 nonselective, and alpha antagonist as well

Which beta-blocker used in HFrEF has the most appreciable blood pressure lowering?

Carvedilol

Which HFrEF GDMT agent must we wait before initiating? What are we waiting for, and why?

Beta-blockers; wait until patient is no longer acutely symptomatic and is euvolemic

• Because beta-blockers can acutely worsen symptoms

How often should beta-blockers be up-titrated when gradually increasing to target / maximally tolerated dose?

Wait AT LEAST 2 weeks after initiation / previous dose increase

Patient status requirement for beta-blocker up-titration?

Stable and euvolemic

What two renal criteria must a HFrEF patient meet to be able to receive an MRA?

Renal criteria:

• eGFR >30 mL/min/1.73m²

• K+ <5 mEq/L

What baseline SCr values are contraindications to MRA use for HFrEF patients?

Men: SCr >2.5 mg/dL

Women: SCr >2.0 mg/dL

When should you discontinue an MRA in a HFrEF patient?

If K+ goes >5.5 mEq/L during MRA treatment

Which MRA causes gynecomastia?

Spironolactone

Which MRA should you switch to in order to help avoid gynecomastia?

Eplerenone

MRA monitoring schedule?

On day 3, on day 7, then monthly for 3 months, then every 3 months

What is the eGFR requirement for initiation of dapagliflozin?

Baseline eGFR ≥25 mL/min/1.73m2

What is the eGFR requirement for initiation of sotagliflozin?

Baseline eGFR ≥25 mL/min/1.73m2

What is the eGFR requirement for initiation of empagliflozin?

Baseline eGFR ≥20 mL/min/1.73m2

What initial effect is usually seen upon initiation of an SGLT2 inhibitor?

Slight, transient worsening of renal function; NOT a reason to d/c

Which HFrEF drug has the “ceiling dose” consideration?

Loop diuretics — beyond a certain dose, they provide no more additional benefit and only increase the ADR risk

• If still not achieving diuresis and euvolemia at ceiling dose, start dosing BID

HFrEF loop diuretic equivalent dosing

Bumetanide 1 mg = torsemide 20 mg = furosemide 40 mg

Which of the HFrEF GDMT meds is not titrated to a guideline-directed specific target dose?

Loop diuretics

• Instead, use the lowest efficacious dose for the patient’s volume overload (if they have volume overload)

Which HFrEF drug should you consider taking an extra dose of if notable weight gain is observed?

Loop diuretic

What parameter should be monitored for loop diuretic efficacy in HFrEF?

Weight

• Increase of 1 lb/day for several days, or increase of 3-5 lb (~2 kg) in a week should prompt evaluation for a loop diuretic dose increase

Which HFrEF drug is associated with quick and acute worsening of symptoms if missed doses?

Loop diuretics

Which HFrEF drug has challenging dosing due to being TID?

Hydralazine/isosorbide dinitrate

Which HFrEF drug is most associated with drug-induced lupus?

Hydralazine/isosorbide dinitrate (specifically the hydralazine component)

Ivabradine use criteria?

• EF ≤35%, NYHA II-III (not studied in class IV)

• Normal sinus rhythm (no afib) with resting HR ≥70 bpm

• Already on max-tolerated beta-blocker dose

How should ivabradine be administered?

With food

Which HFrEF drug is contraindicated with atrial fibrillation?

Ivabradine — must be in sinus rhythm to initiate

What resting heart rate is contraindicated with ivabradine?

<60 bpm (and remember to initiate ivabradine, resting heart rate must be ≥70 bpm — bc ivabradine slows down the heart rate!)

What three medical conditions are ivabradine contraindicated with?

• HFpEF

• Acute decompensated heart failure

• Atrial fibrillation

Ivabradine initiation should be considered in relation to what GDMT med?

Beta-blockers; must be on maximum tolerated beta-blocker therapy (and done with titration stage) before ivabradine is used

Which HFrEF drug is associated with blurred vision (phosphenes)?

Ivabradine

Which HFrEF drug is associated with bradycardia?

Ivabradine

Which HFrEF drug is associated with atrial fibrillation?

Ivabradine

Which HFrEF drug is associated with heart block?

Ivabradine

Vericiguat use criteria

“May consider” if all of the following:

• High-risk HFrEF

  • “High-risk HFrEF” = elevated BNP (>300, or NT-pro-BNP >1000) at baseline

• Worsening HF

  • “Worsening HF” = HF hospitalization within 6 months OR need for outpatient IV diuretics

• On optimized GDMT

Which HFrEF drug is most associated with anemia (Hb, Hct)?

Vericiguat

Which HFrEF drug has an interaction with PDE5 inhibitors (e.g. sildenafil, tadalafil) and should not be administered with them?

Vericiguat — due to hypotension risk

Digoxin use criteria

May consider adding to optimized GDMT if meets one of the two criteria:

• Symptomatic

• Patient unable to tolerate other GDMT

Which HFrEF drug is associated wiht halos/photophobia?

Digoxin

Which HFrEF drug is noted for a narrow therapeutic window?

Digoxin

What increases risk of digoxin toxicity?

Hypokalemia or hypomagnesemia

Digoxin target levels for HFrEF?

0.5-1 mg/dL

• For HFrEF, definitely don’t want ≥1 mg/dL