Starting ENTRESTO for heart failure

Start with sacubitril/valsartan 49/51 mg tabs BID for most patients, or 24/26 mg BID in those with eGFR < 30 mL/min....
Mahitab Hany, BS Pharm, PGDipClinPharm, PGDipClinNutrition

As a cardiovascular pharmacist, you will hear lots of buzz about Entresto, a new drug for systolic heart failure. It's the first "angiotensin receptor neprilysin inhibitor" (ARNI) and combines valsartan with sacubitril. Sacubitril works by inhibiting the enzyme neprilysin. This increases sodium loss and vasodilation and enhances ARB efficacy (see figure 1). This combo is MORE effective than an ACEI alone.

Entresto prevents one cardiovascular (CV) death or heart failure hospitalization for every 21 patients treated over 2 years versus enalapril 10 mg BID. But this benefit comes with trade-offs. The biggest one is hypotension. About 1 in 21 patients have hypotension symptoms with Entresto versus enalapril, and 1 in 77 have a systolic blood pressure (BP) < 90 mmHg. Plus, about 1 in 200 patients may develop angioedema with Entresto versus 1 in 300 on an ACEI. And Entresto will cost about ∼2200 EGP/month.

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Figure (1);
Entresto Mechanisim of Action

Continue to use a standard regimen of an ACEI or ARB, beta-blocker, and an aldosterone antagonist in most patients. Consider REPLACING the ACEI or ARB with Entresto before discharge in patients already titrated to TARGET doses of a standard regimen, with an admission BNP of ≥ 100 pg/mL. But make sure systolic BP is > 100 mmHg.

For patients on an ACEI, wait at least 36 hours after it's stopped before starting Entresto, overlapping them may increase angioedema risk. This doesn't seem to be a concern with ARBs.

Start with sacubitril/valsartan 49/51 mg tabs BID for most patients, or 24/26 mg BID in those with eGFR < 30 mL/min. The 103 mg of valsartan in Entresto is equivalent to 160 mg in Diovan since they are different salts. Avoid Entresto in patients with previous angioedema. And be careful using it in black people, because they're at higher risk for angioedema. For more data, see our notes "Keep NEW heart failure guidelines in mind" and "Overview of heart failure treatment".

References

  • McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. Available at: https://www.nejm.org/doi/10.1056/NEJMoa1409077

    WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240-327. Available at: https://www.ahajournals.org/doi/10.1161/CIR.0b013e31829e8776