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ARNI as First-line Therapy in the Management of Heart Failure

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Dr Bhagirath Raghuraman, Bengaluru    05 January 2018

  1. LCZ696 (Sacubitril+Valsartan) is a first in class ARNI, which simultaneously inhibits neprilysin and blocks AT1 receptor.
  2. Sacubitril, a prodrug inhibits neprilysin → ↑ natriuretic peptide, while valsartan causes direct antagonism of AT II receptors → vasoconstriction, smooth muscle cell proliferation and decreased renal BF.
  3. ARNI should be prescribed in adult patients with systolic HF, patients with NYHA Class II-IV, LVEF <40% on b-blocker and MRA, eGFR >30 ml/min/1.73 m2, SBP >100 mmHg, serum potassium ≤5.2 mmol/L. ARNI should be initiated 36 hours after stopping ACEI, at a dose of 50 mg b.i.d. and doubling the dose every 2-4 weeks till 100 mg b.i.d. is reached. β blockers, MRAs, ivabradine and digoxin can be continued with ARNI, with devices as appropriate. While on ARNI, the patients should be monitored for renal function and serum K. Do not uptitrate if BP >100. BNP is not useful for monitoring as ARNI increases its level.
  4. ARNI is contraindicated in patients with hypersensitivity to any component, history of angioedema related to previous ACEI or ARB therapy, along with ACEIs or concomitantly with aliskiren in patients with diabetes. In PARADIGM-HF, LCZ696 was found to be superior to enalapril in patients with HFrEF. LCZ696 also reduced hospitalization risk for HF by 21% (p < 0.001) and decreased symptoms and limitations of HF (p = 0.001).
  5. The 2016 ACC/AHA/HFSA focused update recommend ARNI along with a BB and MRA as therapy of patients with HFrEF. The guidelines also recommend that ARNI should replace ACEIs when stable patients with mild-to-moderate HF on these therapies have adequate BP and are tolerating these therapies well.

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