Keep NEW heart failure guidelines in mind

As a clinical pharmacist, you should put NEW heart failure guidelines in perspective. Big changes in guidelines will lead to debate about managing heart failure with reduced ejection fraction (HFrEF).

     We’re used to “triple therapy” for HFrEF; an ACEI or ARB, evidence-based beta-blocker (carvedilol, etc), and aldosterone antagonist (spironolactone, etc), to reduce hospitalizations and death. Now Entresto (sacubitril/valsartan) is preferred INSTEAD of an ACEI or ARB when possible, since it prevents hospitalization or cardiovascular (CV) death in about 1 in 21 patients versus an ACEI.

Guidelines also suggest “QUAD therapy”, adding an SGLT2 inhibitor (Forxiga, etc) to triple therapy, regardless of diabetes. This prevents hospitalization or CV death in about 1 in 20 patients. But medication adherence in clinical trials is much higher than in real-world patients. Plus Entresto or an SGLT2 inhibitor are very cost. Also see our note, "Consider heart failure when weighing medications for diabetes".

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Image Source: J Am Coll Cardiol. 2022 May, 79 (17) 1757–1780
Figure 1. Recommendations for Patients With Mildly Reduced LVEF
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Image Source: J Am Coll Cardiol. 2022 May, 79 (17) 1757–1780
Figure 2. Treatment of HFrEF Stages C and D

Continue to focus on optimizing traditional triple therapy first, It can cost very little compared to using Entresto or an SGLT2 inhibitor. And less than 1% of patients with HFrEF are on triple therapy at target doses. Then use shared decision-making to determine whether this new guidance is practical for your patient. If patients still have heart failure symptoms, consider switching from an ACEI or ARB to Entresto. But keep in mind, Entresto is taken BID, and causes low blood pressure (BP) in 1 in 21 patients. Ensure patients wait at least 36 hours after stopping an ACEI if switching to Entresto to reduce risk of angioedema.

If symptomatic patients are already on optimized triple therapy with Entresto or also have type 2 diabetes, think about adding an SGLT2 inhibitor. Benefits are likely a class effect. But weigh SGLT2 inhibitor downsides (genitourinary infections, dehydration, etc). Consider lowering diuretic doses when starting due to risk of hypovolemia and acute kidney injury. Review our note "Overview of heart failure treatment" for more information.

Abbreviations of Figures: ACEi indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; COR, Class of Recommendation; CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; HF, heart failure; HFimpEF, heart failure with improved ejection fraction; HFrEF, heart failure with reduced ejection fraction; hydral-nitrates, hydralazine and isosorbide dinitrate; ICD, implantable cardioverter-defibrillator; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; MRA, mineralocorticoid receptor antagonist; NSR, normal sinus rhythm; NYHA, New York Heart Association; and SGLT2i, sodium-glucose cotransporter 2 inhibitor.

REFERENCES

  • Heidenreich P, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2022 May, 79 (17) e263–e421. Available at: https://doi.org/10.1016/j.jacc.2021.12.012

    Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2022190

    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

    McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. Available at: https://www.nejm.org/doi/10.1056/NEJMoa1911303

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