Valsartan (ARB, angiotensin II receptor antagonist): inhibition of angiotensin-2 receptor + Sacubitril ( neprilysin inhibitor): inhibition of neprilysin and the breakdown of natriuretic peptides (ANP, BNP, bradykinin , etc.)

At HFrEF :

Like ARB, but even more pronounced as the same effects are achieved via 2 systems:

• Vasodilation, blood pressure reduction: afterload reduction with increase in cardiac output.
• Reduction of aldosterone levels.
• Reduction of sodium and water reabsorption in the kidneys: increased sodium excretion and diuresis.
• Reduction of sympathetic activity.
• Reduction of hypertrophy of myocytes and fibrosis in myocardium.
• Increase in LVEF

Trials:

ARNI versus ACE inhibitors : PARADIGM-HF, PIONEER-HF, PROVE-HF

• Reduction of all-cause and cardiovascular mortality
• Reduction of hospitalizations for heart failure
• Reduction of symptoms and better quality of life
• Reduction of sudden death
• Improvement of LVEF

• HFrEF + persistently symptomatic (≥ NYHA II) despite optimal dose of ACE inhibitor / ARB . If necessary, the switch to an ARNI can be made during an admission due to cardiac decompensation.
• Start-up and request for reimbursement by cardiologist.
• The most recent reimbursement criteria in Belgium are:
  • LVEF ≤ 40%
  • And NYHA II-IV
  • Despite optimal dose of ACE inhibitor (or ARB).

Such as the use of ACE inhibitors or ARB.

• PLEASE NOTE: When switching from ACE inhibitor to ARNI, the ARNI may only be taken for the first time more than 36 hours after the last intake of the ACE inhibitor. When starting earlier < 36 hours after the last intake of an ACE inhibitor, there is an increased risk of angioedema and bronchospasm (due to interaction and increase in bradykinin ).
• NOTE: When switching from ARB to ARNI, the ARNI may be started immediately.
• Start in a low dose and, if possible, increase the dose in small steps over the course of weeks ( up-titration ): Start low, go slow.
• Starting dose:
  • Usually 49 mg / 51 mg 2 x 1 per day (= equivalent to valsartan 2 x 80 mg per day).
  • Reduced dose: 24 mg / 26 mg 2 x 1 per day (= equivalent to valsartan 2 x 40 mg per day) if:
    • the patient is only taking a low dose of ACE inhibitor or ARB (< 50% of the target dose).
    • there is a reduced renal function ( eGFR < 40-60 ml/min).
    • there is a tendency to hypotension (< 100-110 mmHg systolic).
    • there is a moderate hepatic impairment.
• Up-titrate every 2 weeks (+ 25% of the target dose) if blood pressure ≥ 95 mmHg systolic (without symptoms of hypotension: orthostatism , dizziness, fatigue, malaise) and potassium ≤ 5.0 mmol / l and GFR ≥ 30 ml / min. The lower the blood pressure or creatinine clearance, the smaller the dose increases with each up-titration (+ 12.5% of the target dose).
• Always try to titrate further in small steps to the target dose (97 mg / 103 mg 2 x 1 per day (= equivalent to valsartan 2 x 160 mg per day)) or the maximum tolerated dose, as long as blood pressure, renal function and kalemia allow this .
• A low dose of ACE inhibitor, ARB, or ARNI is better than none.
• At start-up, a creatinine increase of up to 50% is acceptable as long as the creatinine clearance remains > 20 ml/min. ACE inhibitors and ARB can be safely continued in severe renal impairment (STOP ACEi trial, NEJM 2022). If necessary, consult with the treating cardiologist and/or nephrologist. Before reducing the dose of this medication, it is always best to reduce the dose of diuretics first if there are no signs of fluid retention.

• In case of hyperkalemia > 5.5 mmol / l, it is preferable to start with a peroral potassium binder ( Lokelma or Veltassa ) instead of dose reduction or complete discontinuation of this heart failure therapy. If necessary, consult with the treating cardiologist and/or nephrologist.

• If in doubt, it is best to adjust the therapy in consultation with the treating cardiologist.
• Monitoring of blood pressure, kidney function and potassium is necessary.
• When starting or increasing this therapy, blood pressure may be (temporarily) lower and dizziness may occur if you stand up too quickly ( orthostatism ). Due to habituation, these complaints often disappear after a few days and the dose should therefore not be reduced or stopped too quickly.
• Caution is needed with:
  • a potassium > 5 mmol /l
  • renal impairment with creatinine > 2.5 mg/dl and/or GFR < 30 ml/min
  • hypotension < 90 mmHg systolic
• Caution is still necessary when combining other potassium-enhancing medications: spironolactone , NSAID, etc. See: hyperkalemia.

• Hypotension
• Gastrointestinal: diarrhea, abdominal discomfort,…
• Itch
• Cough
• Renal insufficiency
• Hyperkalemia

• Pregnancy and lactation.
• Known bilateral arteries renal stenosis.