Table 5

Pharmacotherapy for treatment of HFrEF

PharmacotherapyEvidencePopulationRelative risk (%)Number needed to treat2016 ACC/AHA guideline recommendationsSpecial considerations
ACEI/ARBCONSENSUS
SOLVD
Val-HeFT
VALIENT
All patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality11–276.85–22IAARB can be recommended in place of ACEI if patient is intolerant to ACEI because of cough or angiooedema
β-BlockerMERIT-HF
COPERNICUS
Carvedilol HF study
CIBIS I and II
All patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality19–6512–21AMust be one of the following: bisoprolol, carvedilol or sustained-released metoprolol succinate
Mineralocorticoid receptor antagonistRALES
EMPHASIS-HF
All patients with NYHA class II–IV HFrEF to reduce morbidity and mortality41–708.8–9.4IAUse only in patients with Cr ≤2.5 mg/dL in men or Cr ≤2.0 mg/dL in women and potassium <5.0 mEq/L
Hydralazine-isosorbide dinitrateV-HeFT
A-HeFT
African-American patients with NYHA class III–IV HFrEF already receiving ACEI and β-blockers6125IA
AliskirenASTRONAUT
ATMOSPHERE
559Not recommended by ACC/AHA for treatment of heart failure
IvabradineSHIFTChronic symptomatic (NYHA class II–III) stable HFrEF who are receiving GDEM, including β-blocker at maximum tolerated dose, and in NSR with heart rate ≥70 bpm at rest2321IIa B-R
Valsartan/SacubitrilPARADIGM-HFChronic symptomatic (NYHA class II–III) HFrEF who tolerate an ACEI or ARB, replaced by ARNI to reduce morbidity and mortality2020I B-RDo not administer concomitantly with ACEI, within 36 hours of last dose of ACEI, or to patients with history of angiooedema
  • ACC/AHA, American College of Cardiology/American Heart Association; ACEI, ACE inhibitor; A-HeFT, American Heart Failure; ASTRONAUT, Aliskiren Trial on Acute Heart Failure Outcomes; ARB, angiotensin receptor blocker; ATMOSPHERE, Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure; CIBIS, Cardiac Insufficiency Bisoprolol Study; CONSENSUS, Cooperative North Scandinavian Enalapril Survival Study; COPERNICUS, Carvedilol Prospective Randomized Cumulative Survival Study Group; Cr, creatinine; EMPHASIS-HF, Eplerenone in Mild Patients Hospitalized and Survival Study in Heart Failure; GDEM, guideline-directed evaluation and management; HFrEF, Heart Failure with Reduced Ejection Fraction; MERIT-HF, Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure; NSR, normal sinus rhythm; NYHA, New York Heart Association; PARADIGM-HF, Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure; RALES, Randomized Aldactone Evaluation Study; SHIFT, Systolic Heart Failure Treatment with the If inhibitor Ivabradine; SOLVD, Studies of Left Ventricular Dysfunction; Val-HeFT, Valsartan Heart Failure Trial; VALIENT, valsartan in Acute Myocardial Infarction Trial; V-HeFT, Vasodilator Heart Failure.