Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendations See the Online Data Supplement for evidence supporting these recommendations. Recommendations for Renin-Angiotensin System Inhibition With ACE Inhibitor or ARB or ARNI COR LOE Recommendations I ACE: A The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors (Level of Evidence: OR ARBs (Level of Evidence: A),15 18 OR ARNI (Level of Evidence: B-R)19 in conjunction with evidence- based beta blockers,20 22 and aldosterone antagonists in selected patients,23,24 is recommended for patients with chronic HFrEF to reduce morbidity and mortality. ARB: A ARNI: B-R See Online Data 18 20. Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Randomized controlled trials (RCTs) clearly establish the benefits of ACE inhibition in patients with mild, moderate, or severe symptoms of HF and in patients with or without coronary artery disease.9 14 ACE inhibitors can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium. ACE inhibitors also inhibit kininase and increase levels of bradykinin, which can induce cough but also may contribute to their beneficial effect through vasodilation. Angiotensin receptor blockers (ARBs) were developed with the rationale that angiotensin II production continues in the presence of ACE inhibition, driven through alternative enzyme pathways.ARBs do not inhibit kininase and are associated with a much lower incidence of cough and angioedema than ACE inhibitors; but like ACE inhibitors,ARBs should be given with caution to patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium. 