• ACE inhibitors: angiotensin inhibition converting enzyme (ACE), which prevents angiotensin I from being converted into active angiotensin II
• Sartans (ARB, angiotensin II receptor antagonists): inhibition of angiotensin 2 receptor

With HFrEF and to a lesser extent with HFmrEF :

• 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.

Trials:

• ACE Inhibitors vs. Placebo (CONSENSUS, SAVE, ISIS-4, SOLVD, AIRE, TRACE)
• ARB vs. placebo (OPTIMAL, VALIANT, ELITE-II Val- HeFT , CHARM)

With HFrEF and to a lesser extent with HFmrEF :

• Reduction of all-cause and cardiovascular mortality
• Reduction of hospitalizations for heart failure
• Reduction of symptoms and better quality of life
• Slight improvement in LVEF

Always if LVEF ≤ 40% and strongly considered if LVEF ≤ 50%, unless in case of contraindication or intolerance.

• ACE inhibitors remain the first choice therapy.
• ARB: only in case of intolerance to ACE inhibitors (irritating cough).

Note: Heart failure studies in HFrEF have never been conducted with perindopril . Yet perindopril is widely used as a treatment for HFrEF . The effect of ACE inhibitors is considered a class effect. The indication for heart failure is also stated on the package leaflet for perindopril .

• Start with a low dose and, if possible, increase the dose in small steps over the course of weeks ( up-titration ): Start low, go slow. See Table .
• Up-titration every 2 weeks (+ 12.5% or 25% of target dose) as long as blood pressure is ≥ 95-100 mmHg systolic, without symptoms of hypotension ( orthostatism on standing, dizziness, fatigue, malaise) and as long as potassium is ≤ 5.0 mmol /l and the GFR is ≥ 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 to the target dose (see table) or the maximum tolerated dose, as long as blood pressure, renal function and kalamia allow this.
• A low dose of ACE inhibitor (or ARB) is better than no ACE inhibitor (or ARB).
• 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.

• ACE inhibitors: cough and angioedema.
• Hypotension
• Renal insufficiency
• Hyperkalemia

• Pregnancy and lactation.
• Known bilateral A renalis stenosis.
• ACE inhibitors: history of angioedema.