The following are 10 summary points to remember about the 2016 American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) Focused Update on New Pharmacological Therapy for Heart Failure:

1. The ACC/AHA/HFSA guideline update gives a Class I recommendation for the clinical strategy of inhibition of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors (Level of Evidence: A), OR angiotensin-receptor blockers (ARBs) (Level of Evidence: A), OR angiotensin receptor–neprilysin inhibitors (ARNI) (Level of Evidence: B-R) in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients with chronic heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality.
2. The recommendation for ARNI is based on the PARADIGM trial, which reported a 20% reduction in the composite endpoint of cardiovascular death or HF hospitalization—this composite endpoint of cardiovascular death or HF hospitalization was consistent across subgroups.
3. The ACC/AHA/HFSA guideline update gives a Class I recommendation (Level of Evidence: B-R) to replace an ACE inhibitor or ARB by an ARNI in selected patients with chronic symptomatic HFrEF (New York Heart Association [NYHA] class II/III) with an adequate blood pressure who are already tolerating a reasonable dose of ACE inhibitor or ARB.
4. The use of ARNI is associated with the risk of hypotension, renal insufficiency, and a low-frequency incidence of angioedema. Clinical experience will provide further information regarding the optimal titration and tolerability of ARNI, particularly with respect to blood pressure, adjustment of concomitant HF medications, and the rare complication of angioedema.
5. To facilitate initiation and titration, the approved ARNI is available in three doses, which includes a dose that was not tested in the PARADIGM trial. See the package insert for directions of use.
6. The ACC/AHA/HFSA guideline update gives a Class I recommendation (Level of Evidence: A) for the use of ACE inhibitors in patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality. Therefore, for those patients in whom ARNI is not appropriate, the guideline update strongly advises the continued use of an ACE inhibitor for all classes of HFrEF.
7. The ACC/AHA/HFSA guideline update gives a Class I recommendation (Level of Evidence: A) for the use of ARBs in patients with prior or current symptoms of chronic HFrEF and who are intolerant to ACE inhibitors due to cough or angioedema, to reduce morbidity and mortality. Head-to-head comparisons of an ARB versus ARNI for HF do not exist. The guideline update recommends the use of ARBs for those patients in whom an ACE inhibitor or ARNI are inappropriate.
8. The ACC/AHA/AFSA guideline update gives a Class III (harm) recommendation (Level of Evidence: B-R), that is, ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor.
9. The ACC/AHA/HFSA guideline update gives a Class III (harm) recommendation (Level of Evidence: C-EO), that is, ARNI should not be administered in patients with a history of angioedema.
10. The ACC/AHA/HFSA guideline update gives a Class IIa recommendation (Level of Evidence: B-R) for use of ivabradine to reduce HF hospitalization in patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF ≤35%) receiving guideline-directed evaluation and management, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest. The guideline recommends that given the well-proven mortality benefits of beta-blocker therapy, it is important to initiate and uptitrate these agents to target doses, as tolerated, before assessing the resting heart rate for consideration of ivabradine initiation. It was noted that the study patients who had a myocardial infarction within 2 months were excluded.

Keywords: Adrenergic beta-Antagonists, Angioedema, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Geriatrics, Heart Failure, Hypotension, Mineralocorticoid Receptor Antagonists, Neprilysin, Practice Guideline, Primary Prevention, Receptors, Angiotensin, Renal Insufficiency, Renin-Angiotensin System

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