Optimal Management of HFrEF with ARNI Therapy

Evidence-Based Recommendations for HFrEF Management

• The American College of Cardiology recommends switching from losartan (ARB) to an ARNI (sacubitril/valsartan) while continuing carvedilol in patients with Heart Failure with Reduced Ejection Fraction (HFrEF), as this replacement strategy significantly reduces morbidity and mortality 1, 2
• For patients with NYHA class II-III HFrEF who tolerate an ACE inhibitor or ARB, replacement with an ARNI is strongly recommended to further reduce morbidity and mortality (Class 1, Level B-R) 1, 2
• The American Heart Association and American College of Cardiology recommend that ARNIs should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor (Class 3: Harm, Level B-R) 1, 2
• Sacubitril/valsartan (ARNI) significantly reduced the composite endpoint of cardiovascular death or HF hospitalization by 20% compared to enalapril in the PARADIGM-HF trial 2

Beta-Blocker Therapy

• The American College of Cardiology recommends carvedilol as a preferred beta-blocker in patients with HFrEF and should be continued as part of guideline-directed medical therapy 3
• Target doses of beta-blockers should be achieved whenever possible, with carvedilol target dose being 25 mg twice daily for patients <85 kg and 50 mg twice daily for patients >85 kg 4, 5
• Carvedilol may have more favorable effects on glycemic control than metoprolol succinate or bisoprolol in patients with HFrEF and diabetes 6

Important Clinical Considerations

• The American Heart Association, American College of Cardiology, and Heart Failure Society of America guidelines recommend replacement of ACEi or ARB with ARNI, not addition 1, 2
• Sacubitril/valsartan already contains valsartan (an ARB) plus sacubitril (neprilysin inhibitor), making additional ARB therapy (losartan) unnecessary and potentially increasing risk of hypotension 2

Practical Implementation

• When switching from losartan to sacubitril/valsartan, no washout period is required (unlike when switching from ACEi) 2
• Start with appropriate dose of sacubitril/valsartan based on prior ARB dose:
  • If patient is taking equivalent of >160 mg daily of valsartan: start with 49/51 mg twice daily 7
  • If patient is taking lower doses: start with 24/26 mg twice daily 7
• Monitor blood pressure, electrolytes, and renal function after initiation and during titration 7

Common Pitfalls to Avoid

• Combining an ARNI with an ARB (losartan) is not recommended and may increase risk of hypotension and other adverse effects 1, 2
• Underdosing of beta-blockers is common in clinical practice - aim for target doses whenever possible 4, 5