Choice of initial angiotensin system blocker (ARNI, ACE inhibitor, or single agent ARB) in an adult with heart failure with reduced ejection fraction

ACE inhibitor: angiotensin converting enzyme inhibitor; ARB: angiotensin II receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan); HFrEF: heart failure with reduced ejection fraction (left ventricular ejection fraction ≤40%); BNP: B-type natriuretic peptide; SBP: systolic blood pressure.
* Initiation of ARNI therapy is appropriate when these criteria are met only if the patient will have ongoing access to this therapy (eg, cost or copay is not prohibitive for the patient).
¶ Natriuretic thresholds for treatment of HFrEF with sacubitril/valsartan are as follows:

• For outpatients: B-type natriuretic peptide [BNP] level ≥150 pg/mL or N-terminal proBNP [NT-proBNP] ≥600 pg/mL
• For outpatients hospitalized for HF within the previous 12 months and BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL
• For inpatients with acute HF: BNP level ≥400 pg/mL or NT-proBNP ≥1600 pg/mL during current hospitalization

Δ Criteria for hemodynamic stability for ARNI therapy include SBP ≥100 mmHg (for at least 6 hours), no increase in dose of intravenous diuretics in the preceding 6 hours, and no intravenous inotropes in the preceding 24 hours. ARNI therapy should be avoided if there is concern for risk of hypotension in the judgement of the clinician even if the SBP criterion is met. For example, the risk of hypotension may be higher in patients who are very elderly (age >80 years) or frail.
◊ For patients with hypotension and/or worsening renal function, volume status should be assessed to determine whether diuretic therapy should be reduced or held.
§ Refer to UpToDate content on management of hyperkalemia.
¥ Refer to UpToDate content on criteria for transition from ACE inhibitor or ARB to ARNI therapy.