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Dose and schedule of primary pharmacologic therapies for heart failure with reduced ejection fraction in adults

Dose and schedule of primary pharmacologic therapies for heart failure with reduced ejection fraction in adults
Type of therapy Role in therapy Drug Typical initial dose (oral) Target dose Minimum dose titration interval
Renin-angiotensin system inhibitors/neprilysin inhibitors Preferred Sacubitril-valsartan (ARNI) 24/26 to 49/51 mg twice daily* 97/103 mg twice daily Double dose after 1 to 2 weeks or as tolerated
Alternatives Lisinopril 2.5 to 5 mg once daily 20 to 40 mg once daily
Ramipril 1.25 to 2.5 mg once daily 10 mg once daily
Enalapril 2.5 mg twice daily 10 to 20 mg twice daily
Captopril 6.25 mg three times daily 50 mg three times daily
Trandolapril 1 mg once daily 4 mg once daily
Losartan 25 to 50 mg once daily 150 mg once daily
Candesartan 4 to 8 mg once daily 32 mg once daily
Valsartan 20 to 40 mg twice daily 160 mg twice daily
Beta blockers Preferred Carvedilol 3.125 mg twice daily ≤85 kg: 25 mg twice daily Double every 2 weeks
>85 kg: 50 mg twice daily
Carvedilol CR 10 mg once daily 80 mg once daily
Metoprolol succinate CR 12.5 to 25 mg once daily 200 mg once daily
Bisoprolol 1.25 mg once dailyΔ 10 mg once daily
Mineralocorticoid receptor antagonists Preferred Spironolactone 12.5 to 25 mg once daily 25 to 50 mg once daily or in two divided doses Double every 4 weeks
Eplerenone 25 mg once daily 50 mg once daily
SGLT2 inhibitors Preferred Dapagliflozin 10 mg once daily Fixed dose
Empagliflozin 10 mg once daily
Alternative Canagliflozin 100 mg once daily
Only 1 drug from each type of therapy should be used. The drug doses and intervals for dose changes are for patients who do not require dose adjustments due to factors such as comorbid illnesses, kidney or hepatic dysfunction, drug interactions, or other reasons. Consult appropriate UpToDate content, drug monographs included within UpToDate, or other resources to determine the appropriate dosing for a given patient. The drug interactions program included within UpToDate may be used to confirm there are no clinically significant drug interactions. Monitoring of therapy is discussed in UpToDate content on treatment of heart failure with reduced ejection fraction.

ACE: angiotensin converting enzyme; ARB: angiotensin II receptor blocker; ARNI: angiotensin receptor-neprilysin inhibitor; CR: controlled release; HFrEF: heart failure with reduced ejection fraction; SGLT2: sodium-glucose co-transporter 2.

* Selection of initial dose of ARNI is dependent upon whether patient has been treated previously with a moderate to high dose of an ACE inhibitor or ARB; to reduce risk of toxicity, a 36-hour washout period is required if switching from ACE inhibitor to ARNI. Refer to drug monograph included within UpToDate.

¶ Dose increases may be performed more rapidly in a management program or with other forms of monitoring for complications. The requirements for monitoring are described in UpToDate content on pharmacologic therapy for HFrEF.

Δ In the United States, the lowest available bisoprolol tablet strength is 5 mg. A 1.25 mg dose requires splitting a round tablet into quarters, which may be difficult and inaccurate.
Data from: UpToDate Lexidrug. More information available at https://online.lexi.com/.
Graphic 140887 Version 5.0

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