NICE - sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction

Last edited 10/2018

NICE state that:

  • sacubitril valsartan is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction, only in people:
    • with New York Heart Association (NYHA) class II to IV symptoms and
    • with a left ventricular ejection fraction of 35% or less and
    • who are already taking a stable dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor-blockers (ARBs)
  • treatment with sacubitril valsartan should be started by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be performed by the most appropriate team member

Notes:

  • sacubitril valsartan is an angiotensin receptor neprilysin inhibitor, including both a neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (ARB; valsartan). Both sacubitril and valsartan lower blood pressure
    • sacubitril valsartan is a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system
      • neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds
        • drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan)
        • PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction

    • administered orally. The recommended starting dose is one 49/51 mg tablet, twice daily (each tablet contains 48.6 mg sacubitril and 51.4 mg valsartan). The dose should be doubled at 2 to 4 weeks to the target dose of one 97/103 mg tablet (97.2 mg sacubitril and 102.8 mg valsartan) twice daily.Reported adverse events were generally in line with that reported for other medicinal products acting on the renin-angiotensin-aldosterone systems tolerated by the patient

    • most commonly reported adverse reactions during treatment with sacubitril valsartan were hypotension, hyperkalaemia and renal impairment. Reported adverse events were generally in line with that reported for other medicinal products acting on the renin-angiotensin-aldosterone system

    • sacubitril/valsartan should not be given in conjunction with another ARB or renin inhibitor (because of the risk of renal impairment and hyperkalaemia) or an ACE inhibitor (risk of renal impairment, hyperkalaemia and angio-oedema). Due to the potential risk of angio-oedema when used concurrently with an ACE inhibitor, sacubitril/valsartan must not be started for at least 36 h after discontinuing an ACE inhibitor (2)

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