Table 19

Recommendations for Pharmacological Therapy for Management of Stage C HFrEF

RecommendationsCORLOEReferences
Diuretics
 Diuretics are recommended in patients with HFrEF with fluid retentionICN/A
ACE inhibitors
 ACE inhibitors are recommended for all patients with HFrEFIA343,412–414
ARBs
 ARBs are recommended in patients with HFrEF who are ACE inhibitor intolerantIA108,345,415,450
 ARBs are reasonable as alternatives to ACE inhibitors as first-line therapy in HFrEFIIaA451–456
 Addition of an ARB may be considered in persistently symptomatic patients with HFrEF on GDMTIIbA420,457
 Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmfulIII: HarmCN/A
Beta blockers
 Use of 1 of the 3 beta blockers proven to reduce mortality is recommended for all stable patientsIA346,416–419,448
Aldosterone receptor antagonists
 Aldosterone receptor antagonists are recommended in patients with NYHA class II–IV who have LVEF ≤35%IA425,426,478
 Aldosterone receptor antagonists are recommended in patients following an acute MI who have LVEF ≤40% with symptoms of HF or DMIB446
 Inappropriate use of aldosterone receptor antagonists may be harmfulIII: HarmB479,480
Hydralazine and isosorbide dinitrate
 The combination of hydralazine and isosorbide dinitrate is recommended for African Americans with NYHA class III–IV HFrEF on GDMTIA423,424
 A combination of hydralazine and isosorbide dinitrate can be useful in patients with HFrEF who cannot be given ACE inhibitors or ARBsIIaB449
Digoxin
 Digoxin can be beneficial in patients with HFrEFIIaB484–491
Anticoagulation
 Patients with chronic HF with permanent/persistent/paroxysmal AF and an additional risk factor for cardioembolic stroke should receive chronic anticoagulant therapyIA508–514
 The selection of an anticoagulant agent should be individualizedICN/A
 Chronic anticoagulation is reasonable for patients with chronic HF who have permanent/persistent/paroxysmal AF but are without an additional risk factor for cardioembolic strokeIIaB509–511,515–517
 Anticoagulation is not recommended in patients with chronic HFrEF without AF, a prior thromboembolic event, or a cardioembolic sourceIII: No BenefitB518–520
Statins
 Statins are not beneficial as adjunctive therapy when prescribed solely for HFIII: No BenefitA533–538
Omega-3 fatty acids
 Omega-3 PUFA supplementation is reasonable to use as adjunctive therapy in HFrEF or HFpEF patientsIIaB539,540
Other drugs
 Nutritional supplements as treatment for HF are not recommended in HFrEFIII: No BenefitB544,545
 Hormonal therapies other than to correct deficiencies are not recommended in HFrEFIII: No BenefitCN/A
 Drugs known to adversely affect the clinical status of patients with HFrEF are potentially harmful and should be avoided or withdrawnIII: HarmB546–557
 Long-term use of an infusion of a positive inotropic drug is not recommended and may be harmful except as palliationIII: HarmCN/A
Calcium channel blockers
 Calcium channel–blocking drugs are not recommended as routine treatment in HFrEFIII: No BenefitA551,574,575

ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin-receptor blocker; COR, Class of Recommendation; DM, diabetes mellitus; GDMT, guideline-directed medical therapy; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LOE, Level of Evidence; LVEF, left ventricular ejection fraction; MI, myocardial infarction; N/A, not available; NYHA, New York Heart Association; and PUFA, polyunsaturated fatty acids.

  • In the absence of contraindications to anticoagulation.