Table 4

Contraindications and Cautions for Sacubitril/Valsartan and Ivabradine

A) Sacubitril/Valsartan
ContraindicationsCautions
  • Within 36 hours of ACEI use

  • Angioedema with an ACEI or ARB previously

  • Pregnancy

  • Lactation (not recommended)

  • Severe hepatic impairment (Child-Pugh C)

  • Concomitant aliskiren use in patients with diabetes

  • Known hypersensitivity to either ARB or ARNI

  • Renal impairment:

    • - Mild-to-moderate (eGFR ≥30 mL/min/1.73 m2): No starting dose adjustment required

    • - Severe eGFR <30 mL/min/1.73 m2): Reduce starting dose to 24 mg/26 mg twice daily; double the dose every 2–4 weeks to target maintenance dose of 97 mg/103 mg twice daily as tolerated

  • Hepatic impairment:

    • - Mild (Child-Pugh A): No starting dose adjustment required

    • - Moderate (Child-Pugh B): Reduce starting dose to 24 mg/26 mg twice daily; double the dose every 2–4 weeks to target maintenance dose of 97 mg/103 mg twice daily as tolerated

    • - Severe (Child-Pugh C): contraindicated

  • Renal artery stenosis

  • Hypotension

  • Volume depletion

  • Hyponatremia

  • Post myocardial infarction

B) Ivabradine
ContraindicationsCautions
  • HFpEF

  • Presence of angina with normal EF

  • Hypersensitivity

  • Severe hepatic impairment

  • Acute decompensated HF

  • Blood pressure <90/50 mm Hg

  • Sick sinus syndrome without a pacemaker

  • Sinoatrial node block

  • 2nd or 3rd degree block without a pacemaker

  • Resting heart rate <60 bpm

  • Atrial fibrillation or flutter

  • Atrial pacemaker dependence

  • Bradycardia

  • Sinus node disease

  • Cardiac conduction defects

  • Prolonged QT interval

ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; bpm = beats per minute; EF = ejection fraction; eGFR = estimated glomerular filtration rate; HF = heart failure; HFpEF = heart failure with preserved ejection fraction.

  • This population was not studied in PARADIGM HF. The statement is consistent with Food and Drug Administration–approved labeling indications.