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Uptodate Reference Title
Continuing angiotensin system blockade using transition to angiotensin receptor-neprilysin inhibitor therapy for adults with heart failure with reduced ejection
Continuing angiotensin system blockade using transition to angiotensin receptor-neprilysin inhibitor therapy for adults with heart failure with reduced ejection
This algorithm is for use in patients who are already taking an angiotensin system blocker and is intended for use in conjunction with additional UpToDate content on initial management of HFrEF in adults. Refer to UpToDate topics on pharmacologic management of HFrEF in adults for additional details of our approach to treatment and the overall efficacy of these agents.
Initial long-term management of HFrEF includes combined treatment with diuretic therapy (as needed) plus an angiotensin system blocker (ARNI, ACE inhibitor, or single agent ARB) and a beta blocker.
Each patient should take only ONE angiotensin system blocker at a time. If patient has a contraindication for all types of angiotensin system blockers [eg, due to hyperkalemia], then hydralazine plus nitrate is an alternative therapy.
The decision to initiate ARNI depends upon factors including the patient's continuing access to medication and concerns (in the judgement of the clinician) regarding the potential risk of hypotension.
ACE inhibitor: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan); HF: heart failure; HFrEF: heart failure with reduced ejection fraction (left ventricular ejection fraction ≤ 40%); SBP: systolic blood pressure. * 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 adverse effects of ACE inhibitors and ARBs. ¶ In this context, an example of a low dose ACE inhibitor is lisinopril 7.5 mg daily and an example of a low dose ARB is valsartan 40 mg twice daily. History of angioedema (of any cause) is a contraindication for ARNI. ARNI therapy should be avoided if there is concern for 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. Δ ARNI should be initiated only if the patient will have continuous access to medication (cost of medication or copay is not prohibitive for the patient). ◊ It is reasonable to switch to ARNI in a patient with an ACE-inhibitor related cough, with the understanding that the risk of ARNI-related cough in patients with prior ACE inhibitor-related cough is unknown. § The last dose of ACE inhibitor should precede the first dose of ARNI (sacubitril/valsartan) by at least 36 hours due to the risk of angioedema with concurrent therapy. ¥ ACE-inhibitor related cough usually begins one to two weeks after instituting therapy but can be delayed up to six months. In a patient with an ACE inhibitor-related cough, it is reasonable to try ARNI although data on the risk of ARNI-related cough in this setting is unknown. ‡ The patient should be warned that angioedema may recur weeks after discontinuation of the ACE inhibitor. Despite prior concerns about a potential risk of angioedema with ARB therapy, an association between ARB therapy and angioedema has not be found. † After discontinuation of ACE inhibitor, ACE-inhibitor related cough typically resolves within one week but can persist up to four weeks. ** A patient who develops hypotension with ACE inhibitor or ARB despite a euvolemic status may be at risk for developing hypotension with hydralazine plus nitrate therapy.
